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hi everyone

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uh

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thanks for coming to our session today

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thinking beyond luca stem life and

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primordial diversity

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uh so we are going to begin our session

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uh today with a remote lecture

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uh by antonio loscano

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the last universal common ancestor

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thanks antonio

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my pleasure

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i think you can hear me without any

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problem right

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yes we can hear you loud and clear

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lovely thank you so much well first of

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all i want to thank the organizers of

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this session anton greg aaron for

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inviting me and i have to apologize for

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being unable to be there i had a small

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health issue so

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i wasn't able to

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to travel to to atlanta which is a place

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i feel very much at home and let me

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start by

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recalling what i think was an is an

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extraordinary example of scientific

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insight in 1969 when he

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got the position of associate professor

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of microbiology in illinois um

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carlos sent a letter to francis creek

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expressing his idea of using a different

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molecular markers in order to study the

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very early stages of a

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biological evolution of cell evolution

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and if you go uh down the first page of

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his lecture he says something that is

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extraordinary in his in terms of his

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understanding of the basic biological

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processes of contemporary cells and he

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says well if i want to

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study from a molecular perspective

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molecules the obvious choice of molecule

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here lies in the components of the

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translational apparatus and he was very

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right and then afterwards after a few

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years with the extraordinary

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collaboration of

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george fox and mitch sorghing and others

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they came out in a classical paper

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published in 1977 in the journal of

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molecular evolution they came up with

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the idea that in fact in terms of a very

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early divergence

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cells could be classified or could be

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located into one or three major groups

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the archaea that until then not first

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recognizes a monophyletic group the

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bacteria which

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includes all the

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prokaryotes we are familiar with and the

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nuclear cytoplasm of the eukaryotes and

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because of the differences in

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translation and replication between

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these different groups they came to the

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conclusion that these three lines were

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derived from what they called the

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progeny and they gave a very precise

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definition of the progeny it was defined

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originally as a hypothetical biological

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entity ancestral to the tracial lineages

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and that with they say are the

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rudimentary

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imprecise linkage between the genotype

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and phenotype it is it was a system in

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which the separation between genotype

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and phenotype was not complete

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at the time i was traveling quite

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frequently to houston to collaborate

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with john o'rourke in some issues

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related to prebiotic chemistry i had the

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chance to meet and prepare and befriend

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george fox and we actually published uh

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in a book in 1992 what we thought was

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the first

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and most complete with the information

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available of the

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genomic traits of the genetic traits of

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the progeny we actually made a very very

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detailed analysis of the available

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character and we came to the conclusion

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that in fact the

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homology between the different

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components of the rna polymerase of the

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three groups of the elongation factors

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of the ribosomal rna and so on indicated

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that translation was of a modern type we

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found evidence in the three groups of uh

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because of the reports that had been

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published of dna tropisometers two of

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current node biosynthesis and this led

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us to conclude that it was already

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endowed with a dna genome there was

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clearly an epsilon distributed atpase

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found in the three lines and a number of

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um

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of enzymes associated with very basic

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metabolic processes so our conclusion

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was that in fact the project note was

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not sash it was already

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sell very much like the ones that we see

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today now with the explosion of a

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genomic instrument with the

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capability of sequencing very rapidly uh

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genes and genomes and with the

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availability of more rapid

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computers uh in fact the

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attempts to define the so-called project

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or the ancestor of the treatment cell

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domains multiplied and exploded in an

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extraordinary way and you can see in

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this list how the

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ideas the descriptions of the nature of

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the protein are diverse and rose and fox

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had proposed that it was a entity in

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which phenotype and genotype had not yet

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occurred uh

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myself together with george fox and

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general proposed that it was a bacteria

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like cellular entity mushakian and

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kerning proposed that it was a

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cell and dog with an rna genome an idea

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that has impact in fact has been

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repeated by others like patrick for tear

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and so on but what is very surprising is

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the strong differences in our

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descriptions of the progeny some say

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that it was it had like membranes some

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say that it was a network of inorganic

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compartments harboring and leaks of

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virus like genetic elements some say

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that like patrick forte that it was uh

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say i was formed by rna cells that

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acquired dna genomes through

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polyphylactic viral infections and so on

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well when one looks at the methodologies

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behind these descriptions the first

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thing that is surprising is to realize

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that uh there is a confusion between

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cellular sen ancestors and organismal

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sentences which are not quite the same

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every contemporary biomolecule has its

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own history

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that traces back to an individual

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moleculars and ancestor and this

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confusion of course leads to as very uh

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complicated antagonistic definitions of

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what the progenitor means or what the

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less common ancestor means and

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clearly something that has to be kept in

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mind is the reconstruction of the thin

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complement of this look our less common

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ancestor must include traits that

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originated in different evolutionary

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stages in different cells

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now clearly the biases that we have when

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trying to describe the nature of the

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less common ancestor have to do with

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unjustified theoretical assumptions for

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instance the idea that you can

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extrapolate molecular phylogenys back

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into the waters of the primitive soup

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the confusion between ancient and

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primitive people that deny the with some

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people say with very good reasons i

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don't think this is the case the

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existence of an rna protein world

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with very unrealistic definitions of

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primitive environments that include some

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misunderstandings of prebiotic chemistry

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and then we have methodological issues

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like the definitions of sequence ability

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biased sample size primary structure

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based searches undetected gene gain and

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loss including of words and recognized

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lateral gene transfer

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but perhaps the most important thing

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that we have to keep in mind is that

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nowadays the natural the less common

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ancestor should be defined as the nature

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of the ancestor the less common ancestor

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of prokaryotes of bacteria on the one

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hand and the archaea with the nuclear

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cytoplasm as a sister group of bacteria

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and

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we have been trying to in my group in

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mexico we have been trying to

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characterize the traits of this and less

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common ancestor and so far what we have

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is that there is a significant numbers

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of rna-related protein architectures of

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course the obvious are proteins

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associated with

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the ribosome and so on but also many

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many proteins associated with the

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metabolism of rna there are apparent it

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was a modern type of transcription and

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translation a dna genome encoding a wide

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array of repair and recombination

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mechanisms reverse gi rays which in the

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opinion of some colleagues implies a

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thermophilic lifestyle lipid membranes

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although the actual nature of those

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membranes

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remains an open problem for chemic

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chemiosmotic coupling

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a number of um

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enzymes that indicate metabolic pathways

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and so on but

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what is fascinating is to realize that

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when you look at the enzymes of some

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metabolic pathways

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you actually see that we fail to

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recognize and this is a very common

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problem we fail to recognize in when you

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are comparing sequences many

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biosynthetic enzymes and some police

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have attempted to explain this absence

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by assuming that the metabolic pathway

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intermediates were provided by a biotic

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or geochemical processes by

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biosynthesis a prebiotic synthesis that

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took place in the in the primitive

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oceans that

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or perhaps that early metabolic roots

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depended on a spontaneous reaction that

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we know cannot cure in some cases or

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that different organisms were encoding

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different catalysts that were shared by

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multi-directional that protein transfer

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well the problem with some of these

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hypotheses is that if you look at the

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biosynthesis let us say of nucleotides

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what you find is a number of molecules

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are extremely unstable and it's very

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difficult to account for their presence

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in the primitive oceans of the earth or

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the primitive soup or the primitive

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environment whatever you want to

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describe it and i think that one can say

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that yes very likely there were some uh

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semi-enzymatic rules that existed during

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the early stages of cell evolution this

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is an argument that stanley miller and i

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insisted on but

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more in addition one has to say that we

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don't have any good prebiotic synthesis

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of most metabolic intermediates most of

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them are actually quite unstable

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chemically and have very very small have

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life and the bottleneck effects will

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hinder the efficiency of these semi

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enzymatic biosynthetic roots so the

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conclusion is that most likely we don't

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have to appeal to these mechanisms they

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are very very unrealistic biochemically

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chemically geochemically and most likely

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we have been

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failing so far to identify the missing

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enzymes now

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if we go to the issue of the nature of

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the genome of the less common ancestor

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all the evidences that we have collected

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suggests that there was a dna genome

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that was including a wide array of

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repair and recombination mechanisms and

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let me just summarize this and at the

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least the inventory that we have been

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able to complete we have evidence of dna

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repair by reversal of damage we found

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very good evidence for the conservation

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of photolysis for uh photoproliasis

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we found very very good evidence of

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oxygen repair like uracil dna because he

284
00:11:50,389 --> 00:11:47,760
lays

285
00:11:52,710 --> 00:11:50,399
a number of glycosylases excision repair

286
00:11:54,949 --> 00:11:52,720
and so on and we found evidence of

287
00:11:57,110 --> 00:11:54,959
endonucleases associated with uv damage

288
00:11:58,069 --> 00:11:57,120
repair now of course this

289
00:12:01,190 --> 00:11:58,079
is a

290
00:12:03,910 --> 00:12:01,200
not considering the issue of the

291
00:12:06,150 --> 00:12:03,920
possibility of electrical gene transfer

292
00:12:08,389 --> 00:12:06,160
but the question is what was the nature

293
00:12:10,470 --> 00:12:08,399
of the left common ancestor uh we

294
00:12:13,509 --> 00:12:10,480
sincerely believe that the conservation

295
00:12:16,389 --> 00:12:13,519
of so many sequences related to dna

296
00:12:18,470 --> 00:12:16,399
metabolisms and the sequence similarity

297
00:12:20,710 --> 00:12:18,480
served by many ancient proteins suggest

298
00:12:22,790 --> 00:12:20,720
that there was considerable fidelity

299
00:12:25,509 --> 00:12:22,800
already in the genetic system of the

300
00:12:27,750 --> 00:12:25,519
less common ancestor but this similarity

301
00:12:30,710 --> 00:12:27,760
is rarely seen we know that very clearly

302
00:12:33,030 --> 00:12:30,720
from rna genomes such as viral genomes

303
00:12:34,470 --> 00:12:33,040
is rarely conserved

304
00:12:37,590 --> 00:12:34,480
in the case of

305
00:12:39,269 --> 00:12:37,600
sequences encoded by rna and well the

306
00:12:41,590 --> 00:12:39,279
question has been

307
00:12:44,470 --> 00:12:41,600
being raised back and forth a number of

308
00:12:47,590 --> 00:12:44,480
times and in a very interesting paper uh

309
00:12:49,430 --> 00:12:47,600
published uh some 15 years ago pool and

310
00:12:51,910 --> 00:12:49,440
logan raised the possibility that the

311
00:12:54,150 --> 00:12:51,920
less human ancestor was impacted out

312
00:12:55,430 --> 00:12:54,160
with an rna genome

313
00:12:59,030 --> 00:12:55,440
since there was for instance

314
00:13:00,310 --> 00:12:59,040
experimental data demonstrating

315
00:13:03,269 --> 00:13:00,320
that

316
00:13:04,069 --> 00:13:03,279
viral rna genomes can undergo repair by

317
00:13:09,990 --> 00:13:04,079
the

318
00:13:12,069 --> 00:13:10,000
an uh leicester meniscus where an rna

319
00:13:15,110 --> 00:13:12,079
genome is consistent with

320
00:13:17,030 --> 00:13:15,120
uh uh roses proposals that claim that

321
00:13:19,509 --> 00:13:17,040
the less common ancestor was in fact a

322
00:13:22,310 --> 00:13:19,519
highly diverse population of metabolic

323
00:13:25,910 --> 00:13:22,320
complementary cellular progenys with our

324
00:13:28,550 --> 00:13:25,920
small linear rna genomes so is the first

325
00:13:31,590 --> 00:13:28,560
possibility this one suggested uh

326
00:13:34,069 --> 00:13:31,600
mentioned by boolean logan correct well

327
00:13:36,629 --> 00:13:34,079
we do know that in fact dna can be

328
00:13:40,069 --> 00:13:36,639
damaged by alkylation and the bases can

329
00:13:43,430 --> 00:13:40,079
undergo methylation these are very well

330
00:13:45,910 --> 00:13:43,440
described very well understood and we

331
00:13:47,829 --> 00:13:45,920
know of several mechanisms that are

332
00:13:50,310 --> 00:13:47,839
present in

333
00:13:52,710 --> 00:13:50,320
dna

334
00:13:55,509 --> 00:13:52,720
repair of methylation which include the

335
00:13:57,990 --> 00:13:55,519
cutting off the nucleotide

336
00:14:00,069 --> 00:13:58,000
that has been methylated just cutting

337
00:14:03,030 --> 00:14:00,079
off the base that has been methylated

338
00:14:05,430 --> 00:14:03,040
all we know the direct repair mechanisms

339
00:14:07,430 --> 00:14:05,440
that recognize recognize the alkylated

340
00:14:10,550 --> 00:14:07,440
bases which exactly is exactly the

341
00:14:13,430 --> 00:14:10,560
mechanism that was proposed by pull and

342
00:14:14,230 --> 00:14:13,440
logan well let us take a brief look at

343
00:14:17,189 --> 00:14:14,240
these

344
00:14:19,829 --> 00:14:17,199
dna repair mechanisms that recognize the

345
00:14:23,590 --> 00:14:19,839
alkylated bases and yes indeed we have

346
00:14:25,590 --> 00:14:23,600
an enzyme that's a um alfb which is a

347
00:14:28,470 --> 00:14:25,600
monomeric behind the

348
00:14:32,310 --> 00:14:28,480
diode oxygenase the enzyme is very well

349
00:14:35,269 --> 00:14:32,320
characterized it requires iron but the

350
00:14:38,310 --> 00:14:35,279
problem is that the enzymes very

351
00:14:42,069 --> 00:14:38,320
absolutely depends strongly on free

352
00:14:44,310 --> 00:14:42,079
oxygen and clearly

353
00:14:45,910 --> 00:14:44,320
this oxygen was unavailable in the

354
00:14:47,350 --> 00:14:45,920
prebiotic and in the primitive

355
00:14:50,389 --> 00:14:47,360
environment when the less common

356
00:14:53,030 --> 00:14:50,399
ancestor population was floating around

357
00:14:56,230 --> 00:14:53,040
and although it is true that rna can be

358
00:14:58,550 --> 00:14:56,240
methylated rna can be repaired by rb

359
00:15:04,870 --> 00:14:58,560
most likely what we are seeing is a lack

360
00:15:10,829 --> 00:15:08,389
dna and rna associated proteins as was

361
00:15:13,829 --> 00:15:10,839
described in the

362
00:15:15,990 --> 00:15:13,839
1970s by emily super candle and others

363
00:15:18,310 --> 00:15:16,000
so what are our conclusions and our

364
00:15:20,389 --> 00:15:18,320
questions well what we call the

365
00:15:23,030 --> 00:15:20,399
leicester answer was most likely a

366
00:15:25,509 --> 00:15:23,040
population of complex bacterial-like

367
00:15:28,230 --> 00:15:25,519
cells and that with many of the traits

368
00:15:30,790 --> 00:15:28,240
of extreme protect x and prokaryotes it

369
00:15:33,110 --> 00:15:30,800
was neither approaching nor a direct

370
00:15:36,150 --> 00:15:33,120
medium descendant of the rna world if

371
00:15:38,550 --> 00:15:36,160
there was an rna world as soft today

372
00:15:40,550 --> 00:15:38,560
comparative genomics is an essential

373
00:15:43,430 --> 00:15:40,560
tool but it doesn't provide that with

374
00:15:46,069 --> 00:15:43,440
any direct evidence of the rna world

375
00:15:47,590 --> 00:15:46,079
pre-rna world or much less on the origin

376
00:15:49,590 --> 00:15:47,600
of life itself

377
00:15:51,670 --> 00:15:49,600
that i sincerely believe the

378
00:15:54,310 --> 00:15:51,680
reconstruction of the trace of the less

379
00:15:56,470 --> 00:15:54,320
common ancestor requires a clear

380
00:15:59,269 --> 00:15:56,480
understanding of primitive environment

381
00:16:01,269 --> 00:15:59,279
and of chemical realities at that the

382
00:16:03,829 --> 00:16:01,279
origin and early diversification of

383
00:16:05,990 --> 00:16:03,839
light proceeded at a surprisingly rapid

384
00:16:07,749 --> 00:16:06,000
pace and that after what is very

385
00:16:10,230 --> 00:16:07,759
surprising is this is something that

386
00:16:12,310 --> 00:16:10,240
assange miller and i pointed out many

387
00:16:14,310 --> 00:16:12,320
many years ago after the rapid

388
00:16:16,710 --> 00:16:14,320
biological evolution that took place

389
00:16:18,949 --> 00:16:16,720
following the origins of life the basic

390
00:16:21,430 --> 00:16:18,959
genetic traits and major molecular

391
00:16:23,990 --> 00:16:21,440
processes have persisted essentially

392
00:16:26,310 --> 00:16:24,000
unchained for more than 3.5 10 to the

393
00:16:28,470 --> 00:16:26,320
nine years which i think is quite an

394
00:16:30,710 --> 00:16:28,480
extraordinary feat of

395
00:16:39,350 --> 00:16:30,720
biological conservation thank you so

396
00:16:43,189 --> 00:16:41,590
thanks antonio and we have a lot of time

397
00:16:44,710 --> 00:16:43,199
for questions

398
00:16:47,189 --> 00:16:44,720
so um

399
00:16:50,389 --> 00:16:47,199
i don't see any in the chat right now

400
00:16:52,230 --> 00:16:50,399
uh but please come up to the mics and

401
00:16:57,030 --> 00:16:52,240
um ask your questions we have about 15

402
00:16:57,040 --> 00:17:03,189
did i speak so rapidly i'm surprised

403
00:17:03,199 --> 00:17:09,829
maybe i can start with a question

404
00:17:14,150 --> 00:17:12,150
hi nice talk thanks this is jen glass

405
00:17:15,990 --> 00:17:14,160
from georgia tech i'm sorry i missed it

406
00:17:18,309 --> 00:17:16,000
um could you go

407
00:17:20,549 --> 00:17:18,319
could you go back and um i was wondering

408
00:17:22,630 --> 00:17:20,559
about your oxygen story could you just

409
00:17:24,390 --> 00:17:22,640
explain okay

410
00:17:26,710 --> 00:17:24,400
okay so how did it

411
00:17:28,230 --> 00:17:26,720
repair without oxygen can you just go

412
00:17:29,909 --> 00:17:28,240
through that one more time for me if you

413
00:17:32,549 --> 00:17:29,919
wouldn't mind and are there any

414
00:17:36,390 --> 00:17:32,559
alternative theories yeah thanks yeah no

415
00:17:38,710 --> 00:17:36,400
i'll be absolutely delighted well uh dna

416
00:17:41,990 --> 00:17:38,720
the basis and the same is true of rna

417
00:17:43,750 --> 00:17:42,000
bases can be methylated and

418
00:17:46,070 --> 00:17:43,760
you don't want your bases to be

419
00:17:49,430 --> 00:17:46,080
methylated because of you're altering

420
00:17:51,590 --> 00:17:49,440
your genetic information so cells have

421
00:17:53,909 --> 00:17:51,600
the ball

422
00:17:57,110 --> 00:17:53,919
mechanisms to actually

423
00:18:00,070 --> 00:17:57,120
cut off the alkyl groups that can affect

424
00:18:02,470 --> 00:18:00,080
the bases and these mechanisms include

425
00:18:04,870 --> 00:18:02,480
the nucleotide excision repair i mean

426
00:18:09,029 --> 00:18:04,880
you cut off the entire nucleotide and

427
00:18:11,990 --> 00:18:09,039
then um comp er repair it with a a

428
00:18:14,230 --> 00:18:12,000
complementary strand you can just cut

429
00:18:15,830 --> 00:18:14,240
off the base and then that has been

430
00:18:17,990 --> 00:18:15,840
methylated and then the same thing

431
00:18:20,789 --> 00:18:18,000
happens or you can actually have

432
00:18:23,669 --> 00:18:20,799
mechanisms that recognize directly the

433
00:18:25,750 --> 00:18:23,679
alkylated bases which is the mechanisms

434
00:18:26,789 --> 00:18:25,760
that poole and logan were suggesting

435
00:18:28,870 --> 00:18:26,799
could have

436
00:18:30,230 --> 00:18:28,880
play a role in the

437
00:18:33,590 --> 00:18:30,240
in the in

438
00:18:35,830 --> 00:18:33,600
in rna genomes uh well the problem is

439
00:18:38,470 --> 00:18:35,840
that the the enzyme is extremely well

440
00:18:41,590 --> 00:18:38,480
known the domain has been the active

441
00:18:43,990 --> 00:18:41,600
domain of this the dio

442
00:18:46,470 --> 00:18:44,000
has been very very well characterized

443
00:18:49,590 --> 00:18:46,480
the biochemistry is known in exclusive

444
00:18:51,909 --> 00:18:49,600
detail and you require an iron iron two

445
00:18:56,470 --> 00:18:51,919
you require actually this is better you

446
00:18:59,669 --> 00:18:56,480
require um also glutamate which is then

447
00:19:02,549 --> 00:18:59,679
reduced to succinate and

448
00:19:05,430 --> 00:19:02,559
but the problem is that this enzyme

449
00:19:09,029 --> 00:19:05,440
necessarily cannot work in the absence

450
00:19:11,190 --> 00:19:09,039
of free oxygen it is a must there have

451
00:19:14,870 --> 00:19:11,200
been attempts to actually substitute it

452
00:19:18,310 --> 00:19:14,880
by nitrogen two or other components it

453
00:19:22,390 --> 00:19:18,320
simply doesn't work so i think yes this

454
00:19:25,110 --> 00:19:22,400
enzyme can repair methylated rna but

455
00:19:28,470 --> 00:19:25,120
only under oxygen rich conditions which

456
00:19:30,070 --> 00:19:28,480
are extremely unlikely in the very early

457
00:19:32,549 --> 00:19:30,080
stages when

458
00:19:38,549 --> 00:19:32,559
prior to the separation of the archaea

459
00:19:43,029 --> 00:19:41,270
in other words this is a mechanism one

460
00:19:44,230 --> 00:19:43,039
question in chat

461
00:19:47,190 --> 00:19:44,240
so

462
00:19:50,830 --> 00:19:47,200
and then we will go back to

463
00:19:53,029 --> 00:19:50,840
people here so a question from chad

464
00:19:54,789 --> 00:19:53,039
hello louder

465
00:19:57,270 --> 00:19:54,799
closer to the

466
00:19:57,280 --> 00:20:00,870
sorry okay this mic's a little better

467
00:20:05,909 --> 00:20:03,430
uh so we have one question from the chat

468
00:20:08,630 --> 00:20:05,919
uh how do the two types of membrane

469
00:20:10,789 --> 00:20:08,640
lipids fit into the luca problem were

470
00:20:13,270 --> 00:20:10,799
both archaeal and bacterial eukarya

471
00:20:16,470 --> 00:20:13,280
types present from the beginning

472
00:20:19,510 --> 00:20:16,480
it's a major major unresolved issue

473
00:20:21,750 --> 00:20:19,520
people like julie peretto and others

474
00:20:22,630 --> 00:20:21,760
have argued that perhaps the two types

475
00:20:24,630 --> 00:20:22,640
of

476
00:20:26,950 --> 00:20:24,640
ellipses were already present in the

477
00:20:28,870 --> 00:20:26,960
less common ancestor we really do not

478
00:20:31,110 --> 00:20:28,880
know we don't have a good answer for

479
00:20:34,470 --> 00:20:31,120
that question and that

480
00:20:37,430 --> 00:20:34,480
is argued by pedeto and others it could

481
00:20:38,310 --> 00:20:37,440
be that a different uh

482
00:20:40,710 --> 00:20:38,320
uh

483
00:20:43,190 --> 00:20:40,720
evolutionary trait selected for the

484
00:20:44,870 --> 00:20:43,200
separation between the two but i i would

485
00:20:47,510 --> 00:20:44,880
say that that's one of the most

486
00:20:49,669 --> 00:20:47,520
troubling issues that we actually have

487
00:20:51,430 --> 00:20:49,679
when trying to reconstruct the

488
00:20:54,470 --> 00:20:51,440
gene complement of the last common

489
00:20:56,390 --> 00:20:54,480
ancestor uh which is exactly what i have

490
00:20:59,029 --> 00:20:56,400
been concentrating together with my

491
00:21:05,750 --> 00:20:59,039
group on different on different traits

492
00:21:11,590 --> 00:21:07,669
hello tony burnett here from georgia

493
00:21:13,430 --> 00:21:11,600
tech and i was wondering um so we have

494
00:21:15,430 --> 00:21:13,440
this uh

495
00:21:17,590 --> 00:21:15,440
we developed now this notion that the

496
00:21:19,350 --> 00:21:17,600
last universal common ancestor

497
00:21:21,430 --> 00:21:19,360
has lots of

498
00:21:23,110 --> 00:21:21,440
complicated things just like a lot of

499
00:21:26,070 --> 00:21:23,120
modern cells um

500
00:21:28,470 --> 00:21:26,080
i'm wondering what you think of the

501
00:21:29,510 --> 00:21:28,480
relative merits of sort of two different

502
00:21:32,149 --> 00:21:29,520
models

503
00:21:34,710 --> 00:21:32,159
of why luca is

504
00:21:37,669 --> 00:21:34,720
who and when it is like you can have a

505
00:21:40,549 --> 00:21:37,679
model where just attrition over time you

506
00:21:42,549 --> 00:21:40,559
accidentally kill off lineages versus a

507
00:21:46,070 --> 00:21:42,559
model in which shortly before it you

508
00:21:47,909 --> 00:21:46,080
have some kind of an explosive advantage

509
00:21:50,630 --> 00:21:47,919
and uh that's and that could be the

510
00:21:52,549 --> 00:21:50,640
reason that the node is where it is what

511
00:21:54,870 --> 00:21:52,559
do you think of the relative merits of

512
00:21:56,870 --> 00:21:54,880
these two ideas or maybe something else

513
00:22:01,430 --> 00:21:56,880
i haven't thought of

514
00:22:02,789 --> 00:22:01,440
well no what i really think is that

515
00:22:09,029 --> 00:22:02,799
so far

516
00:22:11,909 --> 00:22:09,039
ancestor are are by necessity based on

517
00:22:14,789 --> 00:22:11,919
sequence comparisons which is fine but

518
00:22:17,430 --> 00:22:14,799
the problem is that a sequence by itself

519
00:22:19,350 --> 00:22:17,440
is well a set of sequences is not

520
00:22:22,149 --> 00:22:19,360
telling you the whole story the whole

521
00:22:23,029 --> 00:22:22,159
biology of the system what i think is

522
00:22:25,029 --> 00:22:23,039
that

523
00:22:28,390 --> 00:22:25,039
and i may be completely wrong in this

524
00:22:32,549 --> 00:22:28,400
but i think is that we had uh

525
00:22:35,789 --> 00:22:32,559
uh sales populations that were uh

526
00:22:38,549 --> 00:22:35,799
by accretion of genes by uh gene

527
00:22:41,190 --> 00:22:38,559
duplications and so on were undergoing

528
00:22:42,549 --> 00:22:41,200
very very rapid uh

529
00:22:45,909 --> 00:22:42,559
evolution

530
00:22:48,470 --> 00:22:45,919
and rapid relative to geological times

531
00:22:50,070 --> 00:22:48,480
not necessarily rapidly to the rates of

532
00:22:52,870 --> 00:22:50,080
evolution of

533
00:22:56,549 --> 00:22:52,880
microbes or prokaryotes and then one

534
00:22:58,630 --> 00:22:56,559
line by still unknown reasons uh was the

535
00:23:01,270 --> 00:22:58,640
one that became more successful than the

536
00:23:03,029 --> 00:23:01,280
others but clearly

537
00:23:05,110 --> 00:23:03,039
uh since

538
00:23:07,510 --> 00:23:05,120
lateral gene transfer is a phenomenon

539
00:23:10,070 --> 00:23:07,520
that you cannot completely cut off some

540
00:23:12,070 --> 00:23:10,080
of the genes of those other existing

541
00:23:15,830 --> 00:23:12,080
populations may have survived and may

542
00:23:18,390 --> 00:23:15,840
have made it to the the lca

543
00:23:21,270 --> 00:23:18,400
i don't know if i'm answering properly

544
00:23:23,909 --> 00:23:21,280
your your question but

545
00:23:27,590 --> 00:23:23,919
but i think that one simply has to

546
00:23:31,110 --> 00:23:27,600
realize how quickly uh prokaryotes adapt

547
00:23:34,149 --> 00:23:31,120
to environmental insults to consider

548
00:23:36,870 --> 00:23:34,159
that something equivalent was taking uh

549
00:23:39,029 --> 00:23:36,880
place very very early on

550
00:23:40,549 --> 00:23:39,039
thanks you've answered my question by

551
00:23:42,789 --> 00:23:40,559
saying it is that it's the wrong

552
00:23:45,029 --> 00:23:42,799
question which is a good answer thanks

553
00:23:46,710 --> 00:23:45,039
thank you look it's a stimulating

554
00:23:48,870 --> 00:23:46,720
question

555
00:23:50,630 --> 00:23:48,880
um hello my name is sausan from the

556
00:23:53,029 --> 00:23:50,640
university of arizona

557
00:23:55,029 --> 00:23:53,039
and i was wondering how we can use all

558
00:23:56,870 --> 00:23:55,039
this information about lucas nature to

559
00:23:58,390 --> 00:23:56,880
infer the environment it was in

560
00:24:00,710 --> 00:23:58,400
specifically that in the introduction

561
00:24:02,710 --> 00:24:00,720
you mentioned about how people i think

562
00:24:05,269 --> 00:24:02,720
it was wasted all the inferred reverse

563
00:24:07,430 --> 00:24:05,279
guy rays being traced back to luca and

564
00:24:09,510 --> 00:24:07,440
then a couple of years later catchphole

565
00:24:11,430 --> 00:24:09,520
and four terror were like no

566
00:24:13,669 --> 00:24:11,440
it was a probably horizontal gene

567
00:24:16,470 --> 00:24:13,679
transferred from an archaeal

568
00:24:18,390 --> 00:24:16,480
domain to the bacterial domain and that

569
00:24:20,789 --> 00:24:18,400
just put the whole thermophilic luca

570
00:24:22,470 --> 00:24:20,799
debate even on more

571
00:24:23,909 --> 00:24:22,480
high stance um

572
00:24:27,909 --> 00:24:23,919
and then you mentioned that it might

573
00:24:29,590 --> 00:24:27,919
have a uv radiation repair mechanism

574
00:24:30,950 --> 00:24:29,600
so that means it could have been closer

575
00:24:33,110 --> 00:24:30,960
to the surface and maybe away from

576
00:24:35,590 --> 00:24:33,120
hydrothermal vents as a lot of people do

577
00:24:38,149 --> 00:24:35,600
suggest and i would like your opinion on

578
00:24:40,230 --> 00:24:38,159
how we can reconcile all of this

579
00:24:42,390 --> 00:24:40,240
into where luca or the population of

580
00:24:45,029 --> 00:24:42,400
luca might have existed

581
00:24:47,029 --> 00:24:45,039
well the problem is that to reconcile

582
00:24:49,909 --> 00:24:47,039
the descriptions of the

583
00:24:51,269 --> 00:24:49,919
luca or lca whatever you want to call it

584
00:24:53,510 --> 00:24:51,279
with

585
00:24:55,909 --> 00:24:53,520
our reconstructions of the primitive

586
00:24:57,510 --> 00:24:55,919
environment we will need more detailed

587
00:24:59,909 --> 00:24:57,520
reconstructions of the primitive

588
00:25:02,549 --> 00:24:59,919
environment which we absolutely like i

589
00:25:05,830 --> 00:25:02,559
mean even today we have an argument of

590
00:25:08,549 --> 00:25:05,840
how abundant was co2 in the primitive

591
00:25:11,110 --> 00:25:08,559
atmosphere i think we know for sure that

592
00:25:13,990 --> 00:25:11,120
there was uh the flux of uv light was

593
00:25:16,549 --> 00:25:14,000
higher and then than it is today and

594
00:25:19,909 --> 00:25:16,559
hence one can understand that way the

595
00:25:22,630 --> 00:25:19,919
ability to repair the presence the

596
00:25:25,269 --> 00:25:22,640
universal presence of uv

597
00:25:28,070 --> 00:25:25,279
light damage repair but

598
00:25:30,470 --> 00:25:28,080
i think that the main problem there is

599
00:25:32,710 --> 00:25:30,480
that we don't have a

600
00:25:34,070 --> 00:25:32,720
precise description of the last human

601
00:25:35,510 --> 00:25:34,080
ancestor

602
00:25:38,950 --> 00:25:35,520
there are some things that we know for

603
00:25:41,590 --> 00:25:38,960
sure for instance a higher

604
00:25:43,510 --> 00:25:41,600
flux of uv light

605
00:25:46,950 --> 00:25:43,520
i think that the same would be true for

606
00:25:48,630 --> 00:25:46,960
the absence of oxygen uh especially

607
00:25:50,470 --> 00:25:48,640
prior to the

608
00:25:53,669 --> 00:25:50,480
divergence of the

609
00:25:56,070 --> 00:25:53,679
into archaea and bacteria but other than

610
00:25:57,590 --> 00:25:56,080
that i will be

611
00:25:59,750 --> 00:25:57,600
very very

612
00:26:03,029 --> 00:25:59,760
skeptical of making very strong

613
00:26:06,470 --> 00:26:03,039
statements although i have to say that i

614
00:26:11,350 --> 00:26:06,480
do like the idea of

615
00:26:14,710 --> 00:26:11,360
lca or luca living in lukewarm waters

616
00:26:17,190 --> 00:26:14,720
is this contradictory with the idea of

617
00:26:18,230 --> 00:26:17,200
a hot origin of life no

618
00:26:20,470 --> 00:26:18,240
because

619
00:26:23,190 --> 00:26:20,480
luca is very far removed from the

620
00:26:27,350 --> 00:26:23,200
origins of life if not in time at least

621
00:26:30,950 --> 00:26:28,870
so we have

622
00:26:31,750 --> 00:26:30,960
we have a couple of short questions from

623
00:26:36,390 --> 00:26:31,760
chad

624
00:26:40,070 --> 00:26:39,110
the first one is from fabia or sula by

625
00:26:42,630 --> 00:26:40,080
tutti

626
00:26:45,110 --> 00:26:42,640
how wide spread is the gene i'll be in

627
00:26:47,510 --> 00:26:45,120
prokaryotes today are there any

628
00:26:49,510 --> 00:26:47,520
alternatives to perform the same

629
00:26:51,990 --> 00:26:49,520
same type of repair

630
00:26:53,990 --> 00:26:52,000
it's a very good question the the gene

631
00:26:56,870 --> 00:26:54,000
is extremely extremely widely

632
00:26:59,510 --> 00:26:56,880
distributed it's found also

633
00:27:01,990 --> 00:26:59,520
of course it's present in

634
00:27:05,269 --> 00:27:02,000
a aerobic uh

635
00:27:07,350 --> 00:27:05,279
prokaryote it's extremely abundant in

636
00:27:09,510 --> 00:27:07,360
albi there are

637
00:27:13,430 --> 00:27:09,520
it's absent and that's easy to

638
00:27:16,950 --> 00:27:13,440
understand in a number of parasitic

639
00:27:21,029 --> 00:27:16,960
uh eukaryotes uh that live in in the

640
00:27:23,750 --> 00:27:21,039
guts for instance and the hormone the

641
00:27:27,029 --> 00:27:23,760
homologues of the alpha domain have a

642
00:27:29,990 --> 00:27:27,039
very very wide distribution

643
00:27:31,350 --> 00:27:30,000
a brief question

644
00:27:33,430 --> 00:27:31,360
thank you very much

645
00:27:37,909 --> 00:27:33,440
for your presentation my name is

646
00:27:40,470 --> 00:27:37,919
vladimir sobotin university of wisconsin

647
00:27:42,470 --> 00:27:40,480
you already partially uh

648
00:27:44,070 --> 00:27:42,480
answered my questions that it's the

649
00:27:49,190 --> 00:27:44,080
greatest mystery

650
00:27:55,190 --> 00:27:52,149
appeared in a form bacteria like

651
00:27:56,710 --> 00:27:55,200
ancestral structure already surrounded

652
00:27:59,750 --> 00:27:56,720
by a membrane

653
00:28:02,310 --> 00:27:59,760
and how membranes simultaneously occur

654
00:28:05,029 --> 00:28:02,320
together with information molecules is a

655
00:28:07,830 --> 00:28:05,039
great mystery you said it

656
00:28:10,230 --> 00:28:07,840
but could you imagine uh

657
00:28:13,990 --> 00:28:10,240
evolution of a

658
00:28:16,470 --> 00:28:14,000
membrane compartment themselves like in

659
00:28:18,070 --> 00:28:16,480
a lipid world hypothesis

660
00:28:21,669 --> 00:28:18,080
but as a

661
00:28:24,789 --> 00:28:21,679
sphere or in a form of liposuction

662
00:28:26,789 --> 00:28:24,799
that we know that liposomes can

663
00:28:28,070 --> 00:28:26,799
divide they can fuse

664
00:28:30,789 --> 00:28:28,080
and they can

665
00:28:34,789 --> 00:28:30,799
be in a different level

666
00:28:37,510 --> 00:28:34,799
of a waterproof on a bottom on a top and

667
00:28:40,950 --> 00:28:37,520
they can actually evolve themselves

668
00:28:44,230 --> 00:28:40,960
without any information modules

669
00:28:47,350 --> 00:28:44,240
have you ever considered this hypothesis

670
00:28:50,310 --> 00:28:47,360
and not it itself you're raising up but

671
00:28:52,549 --> 00:28:50,320
i think it's a fascinating issue um i

672
00:28:54,950 --> 00:28:52,559
don't think that mechanism will apply

673
00:28:58,549 --> 00:28:54,960
for the less common ancestor for the

674
00:29:00,870 --> 00:28:58,559
luca but certainly certainly one thing

675
00:29:03,430 --> 00:29:00,880
that biologists have not considered

676
00:29:06,950 --> 00:29:03,440
sufficiently is what is called a

677
00:29:10,230 --> 00:29:06,960
structural heredity which they clearly

678
00:29:13,110 --> 00:29:10,240
is involved in the multiplication of

679
00:29:15,430 --> 00:29:13,120
structures in the absence of a genetic

680
00:29:18,310 --> 00:29:15,440
material a good case will be the

681
00:29:24,470 --> 00:29:18,320
centromeres or centrioles another case

682
00:29:29,350 --> 00:29:26,789
replication with no transmission of

683
00:29:31,909 --> 00:29:29,360
hereditary information which will be

684
00:29:34,950 --> 00:29:31,919
exactly the case of the liposomes i

685
00:29:37,990 --> 00:29:34,960
think this is not denying the key role

686
00:29:39,350 --> 00:29:38,000
that genetic material has in in

687
00:29:42,389 --> 00:29:39,360
evolution in

688
00:29:44,549 --> 00:29:42,399
in continuity in time and you know

689
00:29:46,789 --> 00:29:44,559
opening the possibility of divergence

690
00:29:49,590 --> 00:29:46,799
and adaptation and evolution and

691
00:29:52,789 --> 00:29:49,600
adaptation but clearly it's a mechanism

692
00:29:55,590 --> 00:29:52,799
that i would certainly not uh put away

693
00:29:57,590 --> 00:29:55,600
when thinking of pre-cellular systems

694
00:29:59,909 --> 00:29:57,600
yeah and the next question

695
00:30:02,149 --> 00:29:59,919
uh do you think that heredity of

696
00:30:05,430 --> 00:30:02,159
liposuction would be

697
00:30:08,710 --> 00:30:05,440
present as a quantum of our liposuction

698
00:30:10,870 --> 00:30:08,720
so we are running out of time uh so we

699
00:30:12,950 --> 00:30:10,880
just had time for one question so i

700
00:30:15,510 --> 00:30:12,960
would just want to thank professor

701
00:30:16,710 --> 00:30:15,520
alaskana for his wonderful presentation

702
00:30:19,830 --> 00:30:16,720
and

703
00:30:21,830 --> 00:30:19,840
uh his uh answers to to all these many

704
00:30:24,070 --> 00:30:21,840
questions but we have to move to the

705
00:30:25,510 --> 00:30:24,080
next uh presenter who is timothy

706
00:30:27,909 --> 00:30:25,520
zakowiczky

707
00:30:30,389 --> 00:30:27,919
and who is going to present a talk on

708
00:30:32,549 --> 00:30:30,399
origins of the modern reductive

709
00:30:36,310 --> 00:30:32,559
carboxylic acid cycle in the evolution

710
00:30:36,320 --> 00:30:48,830
thank

711
00:30:59,909 --> 00:30:51,909
you of questions

712
00:31:03,190 --> 00:31:01,269
hello everyone

713
00:31:04,149 --> 00:31:03,200
my name is tim i'm a first year phd

714
00:31:05,909 --> 00:31:04,159
student at the university of

715
00:31:06,870 --> 00:31:05,919
wisconsin-madison

716
00:31:08,549 --> 00:31:06,880
although this work was actually

717
00:31:10,230 --> 00:31:08,559
conducted last summer

718
00:31:13,110 --> 00:31:10,240
during the blue marble space institute

719
00:31:14,630 --> 00:31:13,120
of science young science program

720
00:31:16,389 --> 00:31:14,640
um so the topic of my presentation is

721
00:31:18,710 --> 00:31:16,399
the origins of the modern reductive tca

722
00:31:20,230 --> 00:31:18,720
cycle and the evolution of life

723
00:31:22,870 --> 00:31:20,240
carbon fixation is one of the most

724
00:31:24,230 --> 00:31:22,880
fundamental processes in life today

725
00:31:26,310 --> 00:31:24,240
in simple terms it just involves

726
00:31:29,110 --> 00:31:26,320
incorporation of carbon dioxide from the

727
00:31:31,190 --> 00:31:29,120
atmosphere into biological molecules and

728
00:31:34,630 --> 00:31:31,200
is present in all three domains of life

729
00:31:35,830 --> 00:31:34,640
in archaea bacteria and eukaryotes

730
00:31:37,830 --> 00:31:35,840
and there are actually many different

731
00:31:39,029 --> 00:31:37,840
biochemical pathways with which life can

732
00:31:40,710 --> 00:31:39,039
fix carbon

733
00:31:43,350 --> 00:31:40,720
some of which you might have heard more

734
00:31:46,389 --> 00:31:43,360
about such as the calvin cycle which is

735
00:31:48,230 --> 00:31:46,399
common in cyanobacteria and plants or

736
00:31:50,230 --> 00:31:48,240
the reductive acetyl quay pathway also

737
00:31:51,909 --> 00:31:50,240
known as woodland dial pathway

738
00:31:54,789 --> 00:31:51,919
which is this ancient carbon fixation

739
00:31:57,350 --> 00:31:54,799
pathway present in some mesanogens

740
00:31:59,669 --> 00:31:57,360
but of the main interest to our study

741
00:32:01,750 --> 00:31:59,679
was the reductive tca cycle reductive

742
00:32:03,509 --> 00:32:01,760
tricarboxylic acid cycle which is

743
00:32:05,909 --> 00:32:03,519
basically krebs cycle that runs in

744
00:32:07,750 --> 00:32:05,919
reverse so krebs cycle is oxidative tca

745
00:32:10,950 --> 00:32:07,760
cycle it runs the oxidative direction

746
00:32:13,590 --> 00:32:10,960
and releases co2 and reductive tca

747
00:32:16,470 --> 00:32:13,600
fixates co2 instead

748
00:32:19,029 --> 00:32:16,480
so rtca is a very important biochemical

749
00:32:21,110 --> 00:32:19,039
pathway for the field of origins of life

750
00:32:22,230 --> 00:32:21,120
and astrobiology in general for a few

751
00:32:24,549 --> 00:32:22,240
reasons

752
00:32:26,070 --> 00:32:24,559
first of all our tca is autocatalytic

753
00:32:27,509 --> 00:32:26,080
and autocatalytic pathways are

754
00:32:29,909 --> 00:32:27,519
particularly interesting because they

755
00:32:31,430 --> 00:32:29,919
present a really unique way to rapidly

756
00:32:32,870 --> 00:32:31,440
increase complexity in the prebiotic

757
00:32:35,110 --> 00:32:32,880
setting

758
00:32:37,350 --> 00:32:35,120
and also rtca involves biologically

759
00:32:39,190 --> 00:32:37,360
common metabolites so tricarboxylic

760
00:32:40,870 --> 00:32:39,200
acids that are present in basically all

761
00:32:42,470 --> 00:32:40,880
organisms

762
00:32:44,310 --> 00:32:42,480
and there were studies that have shown

763
00:32:45,750 --> 00:32:44,320
that some reactions of rtc can be

764
00:32:48,630 --> 00:32:45,760
catalyzed without the presence of

765
00:32:50,710 --> 00:32:48,640
enzymes for example using minerals

766
00:32:53,909 --> 00:32:50,720
but of the main interest to our study

767
00:32:56,470 --> 00:32:53,919
was that rtca has a really strange and

768
00:32:58,149 --> 00:32:56,480
patchy phylogenetic distribution it is

769
00:33:01,110 --> 00:32:58,159
present only in a few rare groups of

770
00:33:03,190 --> 00:33:01,120
bacteria and that's it no archaea no

771
00:33:06,070 --> 00:33:03,200
eukaryotes only a few rare groups of

772
00:33:08,310 --> 00:33:06,080
archaea oh bacteria which is not exactly

773
00:33:09,750 --> 00:33:08,320
very consistent with the idea of it

774
00:33:12,149 --> 00:33:09,760
being this really ancient carbon

775
00:33:13,669 --> 00:33:12,159
fixation pathway

776
00:33:14,710 --> 00:33:13,679
so here's what the actual cycle looks

777
00:33:16,310 --> 00:33:14,720
like

778
00:33:18,070 --> 00:33:16,320
first of all you can see that two axle

779
00:33:20,470 --> 00:33:18,080
acetates are produced per one round of

780
00:33:21,509 --> 00:33:20,480
the cycle and this is a catalytic part

781
00:33:23,590 --> 00:33:21,519
of it

782
00:33:25,430 --> 00:33:23,600
um and so one excel acetate is coming

783
00:33:27,110 --> 00:33:25,440
from pyruvate carboxylation

784
00:33:29,750 --> 00:33:27,120
and the other one from the cleavage of

785
00:33:33,269 --> 00:33:31,430
and also you can see the three

786
00:33:34,630 --> 00:33:33,279
irreversible steps of the cycle that are

787
00:33:37,110 --> 00:33:34,640
catalyzed differently from their

788
00:33:39,590 --> 00:33:37,120
counterparts in oxidative tca so two of

789
00:33:41,350 --> 00:33:39,600
them are marked in red here

790
00:33:43,350 --> 00:33:41,360
and the third one is actually this

791
00:33:45,350 --> 00:33:43,360
reaction which is the reaction of

792
00:33:46,710 --> 00:33:45,360
citrate cleavage to oxaloacetate and

793
00:33:50,310 --> 00:33:46,720
acetyl-coa

794
00:33:52,310 --> 00:33:50,320
um which is also key because it enables

795
00:33:55,110 --> 00:33:52,320
the auto-catalytic part of the rtca

796
00:33:59,430 --> 00:33:56,870
and there are actually two distinct ways

797
00:34:01,669 --> 00:33:59,440
citrate can be citrate can be cleaved

798
00:34:04,149 --> 00:34:01,679
um the first way is just a simple one

799
00:34:06,710 --> 00:34:04,159
enzyme reaction using the enzyme acl or

800
00:34:08,310 --> 00:34:06,720
atp citrate lyse which just cleaves

801
00:34:09,430 --> 00:34:08,320
citrate into acetyl-coa and excel

802
00:34:11,270 --> 00:34:09,440
acetate

803
00:34:12,710 --> 00:34:11,280
uh and the second way is actually when

804
00:34:15,510 --> 00:34:12,720
citrate is first converted into

805
00:34:18,310 --> 00:34:15,520
acetyl-coa intermediate using ccs or

806
00:34:20,710 --> 00:34:18,320
citric acintase and then cedric way is

807
00:34:23,109 --> 00:34:20,720
cleaved by citral coil ias into

808
00:34:24,550 --> 00:34:23,119
acetyl-coa and oxaloacetate

809
00:34:27,669 --> 00:34:24,560
and here you can also see the reverse

810
00:34:30,389 --> 00:34:27,679
reaction of cs or citrate syntase that

811
00:34:34,629 --> 00:34:30,399
catalyzes while the synthesis of citrate

812
00:34:37,669 --> 00:34:34,639
which is just a simple one-step process

813
00:34:39,669 --> 00:34:37,679
so here is a pattern of how all the

814
00:34:41,829 --> 00:34:39,679
enzymes that i just mentioned with a lot

815
00:34:43,669 --> 00:34:41,839
of abbreviations are related to each

816
00:34:45,829 --> 00:34:43,679
other um some of this is from the

817
00:34:47,669 --> 00:34:45,839
literature and we've also our findings

818
00:34:48,550 --> 00:34:47,679
also confirmed the scheme

819
00:34:51,190 --> 00:34:48,560
so

820
00:34:52,950 --> 00:34:51,200
first of all you can see the two enzyme

821
00:34:55,510 --> 00:34:52,960
system which is often proposed to be

822
00:34:58,550 --> 00:34:55,520
ancestral so you have the enzyme ccs

823
00:35:00,829 --> 00:34:58,560
that produces citrul coa citrocyntase

824
00:35:02,390 --> 00:35:00,839
and ccl which leaves citrul

825
00:35:04,870 --> 00:35:02,400
citracle

826
00:35:06,790 --> 00:35:04,880
and is present in only a few rare groups

827
00:35:08,069 --> 00:35:06,800
of bacteria

828
00:35:11,109 --> 00:35:08,079
also

829
00:35:14,310 --> 00:35:11,119
these two enzymes ccs and ccl have

830
00:35:18,069 --> 00:35:14,320
homologs among other gca enzymes for

831
00:35:20,430 --> 00:35:18,079
example ccs is homologous to scs or

832
00:35:24,390 --> 00:35:20,440
suknokoisentase which catalyzes

833
00:35:27,349 --> 00:35:24,400
succincoasynthesis or breakdown in

834
00:35:29,829 --> 00:35:27,359
both oxidative and reductive tca

835
00:35:31,910 --> 00:35:29,839
and then ccl is homologous to citrate

836
00:35:34,150 --> 00:35:31,920
synthase which is an enzyme exclusively

837
00:35:35,910 --> 00:35:34,160
unique to oxidative tca that catalyzes

838
00:35:38,310 --> 00:35:35,920
citrate synthesis

839
00:35:40,390 --> 00:35:38,320
and subsequently so also looking at

840
00:35:42,230 --> 00:35:40,400
homologs here is especially important

841
00:35:43,910 --> 00:35:42,240
because they're much more common than

842
00:35:45,750 --> 00:35:43,920
the actual citric cleavage enzymes and

843
00:35:47,349 --> 00:35:45,760
did not experience as many losses in

844
00:35:48,950 --> 00:35:47,359
their evolutionary history so we can

845
00:35:51,030 --> 00:35:48,960
infer a lot more from looking at their

846
00:35:53,670 --> 00:35:51,040
evolution

847
00:35:56,390 --> 00:35:53,680
and the last citric cleavage system is

848
00:35:58,470 --> 00:35:56,400
the more derived one enzyme system that

849
00:36:00,550 --> 00:35:58,480
is just acl that first started out as a

850
00:36:02,390 --> 00:36:00,560
two subunit enzyme uh that still

851
00:36:04,310 --> 00:36:02,400
catalyzed the one step reaction without

852
00:36:07,349 --> 00:36:04,320
the citroclase intermediate

853
00:36:10,470 --> 00:36:07,359
and this resulted from fusion of cc one

854
00:36:12,710 --> 00:36:10,480
of the subunits of ccs and ccl so this

855
00:36:14,790 --> 00:36:12,720
is the intermediary step basically

856
00:36:17,349 --> 00:36:14,800
and then the two subunits of icl fused

857
00:36:20,950 --> 00:36:17,359
again in eukaryotes and you get just one

858
00:36:22,950 --> 00:36:20,960
subunit enzyme that does the same thing

859
00:36:24,870 --> 00:36:22,960
so in order to investigate the rarity of

860
00:36:26,390 --> 00:36:24,880
this key reaction we try to do a survey

861
00:36:27,670 --> 00:36:26,400
of is as distribution

862
00:36:29,510 --> 00:36:27,680
and

863
00:36:31,430 --> 00:36:29,520
flow genetic analysis using various

864
00:36:35,109 --> 00:36:31,440
databases such as keg

865
00:36:36,870 --> 00:36:35,119
and cbi genbank or syntax

866
00:36:38,710 --> 00:36:36,880
so first of all what we found is that

867
00:36:40,790 --> 00:36:38,720
the distribution so here are some of our

868
00:36:42,550 --> 00:36:40,800
findings regarding the distribution of

869
00:36:43,910 --> 00:36:42,560
acidic cleavage reaction overlaid on the

870
00:36:46,069 --> 00:36:43,920
tree of life

871
00:36:49,190 --> 00:36:46,079
and you can see a few things here

872
00:36:51,109 --> 00:36:49,200
so first of all we identified a few

873
00:36:52,870 --> 00:36:51,119
taxa in which complete rtc is

874
00:36:55,270 --> 00:36:52,880
theoretically possible at least they

875
00:36:57,589 --> 00:36:55,280
have all the necessary enzymes for that

876
00:36:59,990 --> 00:36:57,599
and note that there is only one archaeon

877
00:37:01,750 --> 00:37:00,000
the microarchite

878
00:37:03,510 --> 00:37:01,760
and it's basically the only archaeon we

879
00:37:06,390 --> 00:37:03,520
found we found that could even

880
00:37:08,630 --> 00:37:06,400
theoretically have our tca

881
00:37:10,310 --> 00:37:08,640
but the main finding is that it's from

882
00:37:12,870 --> 00:37:10,320
this it's really unclear which of the

883
00:37:16,230 --> 00:37:12,880
ancestors had which enzyme and how this

884
00:37:18,390 --> 00:37:16,240
whole system evolved as a whole

885
00:37:20,310 --> 00:37:18,400
but what is interesting is that most

886
00:37:22,790 --> 00:37:20,320
taxa that had the two enzyme systems so

887
00:37:24,550 --> 00:37:22,800
ccs and ccl actually were oxygen

888
00:37:26,790 --> 00:37:24,560
tolerant thermophiles with incomplete

889
00:37:29,190 --> 00:37:26,800
tca so incomplete

890
00:37:30,710 --> 00:37:29,200
either oxidative or reductive tca

891
00:37:32,550 --> 00:37:30,720
and it what's particularly interesting

892
00:37:35,510 --> 00:37:32,560
is oxygen tolerance defined here is both

893
00:37:37,030 --> 00:37:35,520
aerobes and microarea files because it's

894
00:37:39,109 --> 00:37:37,040
really strange that the ancestral form

895
00:37:40,230 --> 00:37:39,119
of the supposedly ancient reaction is

896
00:37:43,910 --> 00:37:40,240
actually mostly present in

897
00:37:47,190 --> 00:37:45,910
um then we looked at the phalagenese and

898
00:37:49,430 --> 00:37:47,200
i believe i don't have enough time to

899
00:37:52,069 --> 00:37:49,440
get into too much detail with these but

900
00:37:53,670 --> 00:37:52,079
the main takeaway is that as you can see

901
00:37:56,230 --> 00:37:53,680
there are very few monophyletic groups

902
00:37:57,670 --> 00:37:56,240
when athletic taxonomic groups here

903
00:37:59,270 --> 00:37:57,680
which indicates there were likely

904
00:38:00,630 --> 00:37:59,280
abundant horizontal gene transfers in

905
00:38:03,109 --> 00:38:00,640
the evolutionary history of these

906
00:38:05,270 --> 00:38:03,119
enzymes so this is the phylogeny of acl

907
00:38:09,109 --> 00:38:05,280
the one enzyme system and this is a

908
00:38:12,150 --> 00:38:09,119
phylogeny of ccl partici and is homolog

909
00:38:14,710 --> 00:38:13,030
with

910
00:38:16,230 --> 00:38:14,720
succinyl quasantes though it's a little

911
00:38:18,470 --> 00:38:16,240
bit more interesting

912
00:38:21,109 --> 00:38:18,480
because what we see is that multiple

913
00:38:23,910 --> 00:38:21,119
distantly related citric cleaving clades

914
00:38:24,950 --> 00:38:23,920
actually have monophyletic scs

915
00:38:27,430 --> 00:38:24,960
so

916
00:38:29,750 --> 00:38:27,440
this implies either that succinoque

917
00:38:31,190 --> 00:38:29,760
synthase is capable of central coe

918
00:38:32,870 --> 00:38:31,200
synthesis as well

919
00:38:34,390 --> 00:38:32,880
which was empirically demonstrated to

920
00:38:36,310 --> 00:38:34,400
not be the case

921
00:38:39,109 --> 00:38:36,320
uh at least with a few central quay

922
00:38:41,109 --> 00:38:39,119
synthases that we know of empirically

923
00:38:42,390 --> 00:38:41,119
um and therefore the likely conclusion

924
00:38:44,150 --> 00:38:42,400
is that it was due to horizontal gene

925
00:38:46,630 --> 00:38:44,160
transfer event or a sequence of events

926
00:38:48,870 --> 00:38:46,640
from a similar source organism

927
00:38:50,390 --> 00:38:48,880
and also adding to that

928
00:38:52,710 --> 00:38:50,400
as we found by looking at synteny for

929
00:38:54,310 --> 00:38:52,720
all these organisms tca related genes

930
00:38:55,990 --> 00:38:54,320
are often located in close proximity to

931
00:38:58,069 --> 00:38:56,000
each other in the genomes

932
00:38:59,990 --> 00:38:58,079
which increases the likelihood of some

933
00:39:02,550 --> 00:39:00,000
kinds of linked transfers linked

934
00:39:04,550 --> 00:39:02,560
horizontal gene transfer events

935
00:39:06,630 --> 00:39:04,560
which in general implies that civic

936
00:39:09,030 --> 00:39:06,640
cleavage was might have been also

937
00:39:10,790 --> 00:39:09,040
obtained horizontally linked to scs in

938
00:39:12,630 --> 00:39:10,800
these organisms in these bacteria

939
00:39:14,150 --> 00:39:12,640
specifically again we don't see this

940
00:39:17,190 --> 00:39:14,160
pattern in archaea that have citric

941
00:39:18,710 --> 00:39:17,200
cleavage but don't have complete rtca

942
00:39:20,550 --> 00:39:18,720
albeit it is important to mention that

943
00:39:22,150 --> 00:39:20,560
deep time horizontal gene transfers are

944
00:39:24,150 --> 00:39:22,160
next to impossible to definitively

945
00:39:26,390 --> 00:39:24,160
resolve particularly since parametric

946
00:39:29,109 --> 00:39:26,400
methods of inferno agts such as

947
00:39:30,870 --> 00:39:29,119
comparing gc content or cotton bias just

948
00:39:32,230 --> 00:39:30,880
don't work here because we're talking

949
00:39:34,550 --> 00:39:32,240
about events that could have happened

950
00:39:37,829 --> 00:39:34,560
billions of years ago

951
00:39:39,349 --> 00:39:37,839
so this is basically all we have

952
00:39:42,069 --> 00:39:39,359
another interesting implication of our

953
00:39:44,390 --> 00:39:42,079
findings are in regards to the evolution

954
00:39:46,630 --> 00:39:44,400
of metabolic mutualism or syntrophy uh

955
00:39:48,470 --> 00:39:46,640
especially in the case of rtca so let's

956
00:39:50,069 --> 00:39:48,480
look at this example first and establish

957
00:39:52,550 --> 00:39:50,079
the ectosymbiotic relationship between

958
00:39:54,710 --> 00:39:52,560
nanohalarkia and halarkia both groups of

959
00:39:58,150 --> 00:39:54,720
archaea that inhabit highly saline

960
00:40:00,470 --> 00:39:58,160
environments and what we see is really

961
00:40:03,030 --> 00:40:00,480
interesting so halorequia a really

962
00:40:05,750 --> 00:40:03,040
well-known and well-established group

963
00:40:08,550 --> 00:40:05,760
have basically all rtca enzymes with

964
00:40:10,630 --> 00:40:08,560
exceptional one or one enzyme system uh

965
00:40:12,950 --> 00:40:10,640
the system for citric cleavage

966
00:40:15,589 --> 00:40:12,960
while nanohilarchia which are frequently

967
00:40:17,270 --> 00:40:15,599
known to be their ectosymbians

968
00:40:19,430 --> 00:40:17,280
are known to only have citric cleavage

969
00:40:22,470 --> 00:40:19,440
enzymes particularly of the two enzymes

970
00:40:24,150 --> 00:40:22,480
the two enzyme system of ccs and ccl

971
00:40:25,750 --> 00:40:24,160
which implies of course a possibility

972
00:40:27,990 --> 00:40:25,760
that there could have been could be some

973
00:40:29,589 --> 00:40:28,000
kind of centrifuge going on with citrate

974
00:40:31,990 --> 00:40:29,599
being transferred from one archaean to

975
00:40:33,510 --> 00:40:32,000
another and the product like excellent

976
00:40:35,430 --> 00:40:33,520
state or acetyl-coa being transferred

977
00:40:37,829 --> 00:40:35,440
back and there are actually multiple

978
00:40:39,670 --> 00:40:37,839
suitable transporters in both organisms

979
00:40:41,829 --> 00:40:39,680
and this is obviously speculative and

980
00:40:43,990 --> 00:40:41,839
requires empirical validation but we see

981
00:40:46,309 --> 00:40:44,000
a very similar pattern for a lot of

982
00:40:48,870 --> 00:40:46,319
other groups of syntrophic partners in

983
00:40:51,510 --> 00:40:48,880
our study such as asgar kian misanogens

984
00:40:53,829 --> 00:40:51,520
or microarchites and certain plasmas and

985
00:40:56,150 --> 00:40:53,839
a few other groups as well um so this is

986
00:40:59,510 --> 00:40:56,160
not just unique to halo or kia although

987
00:41:01,109 --> 00:40:59,520
yes it does require empirical validation

988
00:41:03,190 --> 00:41:01,119
but why is interesting specifically with

989
00:41:05,349 --> 00:41:03,200
scalar kia is because it actually adds

990
00:41:08,069 --> 00:41:05,359
more context to one previously proposed

991
00:41:09,510 --> 00:41:08,079
idea or the purple earth hypothesis

992
00:41:11,430 --> 00:41:09,520
which basically states that due to

993
00:41:14,390 --> 00:41:11,440
spectral complementarity of halo kill

994
00:41:16,870 --> 00:41:14,400
bacteriodopsins so mark here

995
00:41:18,230 --> 00:41:16,880
and chlorophylls

996
00:41:19,589 --> 00:41:18,240
the evolution of the latter could have

997
00:41:21,750 --> 00:41:19,599
happened due to the competition for

998
00:41:23,109 --> 00:41:21,760
wavelengths with retinal phototrophs so

999
00:41:25,109 --> 00:41:23,119
like halo archaea again that use

1000
00:41:26,950 --> 00:41:25,119
bacteriodopsins which have a retinal

1001
00:41:28,390 --> 00:41:26,960
pigment

1002
00:41:29,990 --> 00:41:28,400
but this is complicated by the fact that

1003
00:41:31,270 --> 00:41:30,000
there is no carbon fixation in modern

1004
00:41:33,430 --> 00:41:31,280
halo archaea

1005
00:41:34,950 --> 00:41:33,440
so there's no coupling of a process that

1006
00:41:36,550 --> 00:41:34,960
produces a lot of reducing equivalents

1007
00:41:38,950 --> 00:41:36,560
like photosynthesis the process that

1008
00:41:39,910 --> 00:41:38,960
requires them like carbon fixation

1009
00:41:41,109 --> 00:41:39,920
and

1010
00:41:42,630 --> 00:41:41,119
our findings provide a possible

1011
00:41:45,589 --> 00:41:42,640
explanation for that either so possible

1012
00:41:47,349 --> 00:41:45,599
rtc in the past or and therefore serious

1013
00:41:49,270 --> 00:41:47,359
cleavage enzymes in nanohero kia being

1014
00:41:50,790 --> 00:41:49,280
acquired horizontally

1015
00:41:52,390 --> 00:41:50,800
or just through rtc operating

1016
00:41:54,230 --> 00:41:52,400
syntrophically

1017
00:41:55,750 --> 00:41:54,240
and we also discussed a little bit about

1018
00:41:57,030 --> 00:41:55,760
how syntrophy could be in general

1019
00:41:57,829 --> 00:41:57,040
important for the field of origins of

1020
00:41:59,109 --> 00:41:57,839
life

1021
00:42:01,270 --> 00:41:59,119
because it's significantly more common

1022
00:42:03,109 --> 00:42:01,280
than expected and was shown to be

1023
00:42:04,230 --> 00:42:03,119
product of selection rather than random

1024
00:42:06,150 --> 00:42:04,240
losses

1025
00:42:07,990 --> 00:42:06,160
um and there are even a few lines of

1026
00:42:09,190 --> 00:42:08,000
evidence for the prevalence of syntropic

1027
00:42:11,030 --> 00:42:09,200
interactions early in the evolution of

1028
00:42:12,550 --> 00:42:11,040
life as well

1029
00:42:14,470 --> 00:42:12,560
so basically our main conclusions are

1030
00:42:16,790 --> 00:42:14,480
that citric leavage in modern bacteria

1031
00:42:18,470 --> 00:42:16,800
possessing rtca is likely a consequence

1032
00:42:20,069 --> 00:42:18,480
of deep time horizontal gene transfers

1033
00:42:22,790 --> 00:42:20,079
and therefore modern distribution of

1034
00:42:24,230 --> 00:42:22,800
rtca might not reflect its origins

1035
00:42:25,430 --> 00:42:24,240
and that syntropic interactions might

1036
00:42:27,190 --> 00:42:25,440
have played a role in the evolution of

1037
00:42:28,390 --> 00:42:27,200
our dca origins of life as a whole as

1038
00:42:30,390 --> 00:42:28,400
well

1039
00:42:32,309 --> 00:42:30,400
and as i mentioned this project was

1040
00:42:33,829 --> 00:42:32,319
started doing the the msi asean

1041
00:42:37,670 --> 00:42:33,839
scientist program and i would like to

1042
00:42:38,870 --> 00:42:37,680
thank the whole um the sarma lab for

1043
00:42:39,750 --> 00:42:38,880
all the help and feedback on this

1044
00:42:46,470 --> 00:42:39,760
project

1045
00:42:53,910 --> 00:42:48,630
thank you we have a time for one short

1046
00:42:59,109 --> 00:42:56,710
hi oh god that was a great talk uh julie

1047
00:43:00,390 --> 00:42:59,119
huber from woodsault oceanographic and i

1048
00:43:02,550 --> 00:43:00,400
just want to say this is why i like

1049
00:43:04,309 --> 00:43:02,560
coming to these meetings because

1050
00:43:06,390 --> 00:43:04,319
your rare

1051
00:43:08,710 --> 00:43:06,400
you know organisms are the most abundant

1052
00:43:10,950 --> 00:43:08,720
organisms at deepsea hydrothermal vents

1053
00:43:12,870 --> 00:43:10,960
and i was curious you know when we

1054
00:43:14,309 --> 00:43:12,880
sequence these environments over half of

1055
00:43:15,750 --> 00:43:14,319
half of them are epsilons and

1056
00:43:17,750 --> 00:43:15,760
aquificailys

1057
00:43:19,670 --> 00:43:17,760
and i was wondering if any of the

1058
00:43:22,390 --> 00:43:19,680
metagenome assembled genomes that we're

1059
00:43:23,990 --> 00:43:22,400
pulling out of these natural ecosystems

1060
00:43:25,910 --> 00:43:24,000
that represent way more than the culture

1061
00:43:28,230 --> 00:43:25,920
diversity if they can be incorporated

1062
00:43:30,230 --> 00:43:28,240
into your work

1063
00:43:33,349 --> 00:43:30,240
thank you for your question uh yes i was

1064
00:43:35,349 --> 00:43:33,359
trying to largely avoid uh environmental

1065
00:43:37,349 --> 00:43:35,359
assemblies just because a lot of it is

1066
00:43:39,349 --> 00:43:37,359
uncultured and it really pains me every

1067
00:43:40,790 --> 00:43:39,359
time i see a good enzyme that is just

1068
00:43:43,030 --> 00:43:40,800
from something that's

1069
00:43:44,630 --> 00:43:43,040
not very well known um

1070
00:43:46,069 --> 00:43:44,640
but yeah i think i only incorporated a

1071
00:43:50,069 --> 00:43:46,079
few

1072
00:43:51,910 --> 00:43:50,079
from a more well-known taxa uh at least

1073
00:43:53,430 --> 00:43:51,920
from a literature perspective but yeah

1074
00:43:55,589 --> 00:43:53,440
they're definitely rtc could definitely

1075
00:43:56,790 --> 00:43:55,599
be significantly more distributed and

1076
00:43:58,630 --> 00:43:56,800
actually one of the ideas that was

1077
00:44:00,150 --> 00:43:58,640
previously proposed as well was that it

1078
00:44:02,309 --> 00:44:00,160
originated in archaea instead of

1079
00:44:04,069 --> 00:44:02,319
bacteria even though it's now entirely

1080
00:44:05,349 --> 00:44:04,079
absent in archaea which could

1081
00:44:07,030 --> 00:44:05,359
potentially suggest that there could

1082
00:44:09,190 --> 00:44:07,040
have been some kind of lineage that we

1083
00:44:11,750 --> 00:44:09,200
either don't know about or that just

1084
00:44:13,829 --> 00:44:11,760
died out at some point

1085
00:44:16,630 --> 00:44:13,839
that possessed the cycle and then

1086
00:44:18,309 --> 00:44:16,640
transferred it to modern bacteria

1087
00:44:20,630 --> 00:44:18,319
so yeah looking at environmental

1088
00:44:22,790 --> 00:44:20,640
metagenomes is definitely really

1089
00:44:26,069 --> 00:44:22,800
interesting especially for for this kind

1090
00:44:29,190 --> 00:44:28,150
do you have more questions

1091
00:44:30,550 --> 00:44:29,200
okay

1092
00:44:32,630 --> 00:44:30,560
thank you kim

1093
00:44:36,150 --> 00:44:32,640
and we'd like to move into the next

1094
00:44:38,309 --> 00:44:36,160
speaker uh who is uh veronica merizewski

1095
00:44:41,510 --> 00:44:38,319
and she is going to be talking about

1096
00:44:43,910 --> 00:44:41,520
scaling patterns in enzyme diversity and

1097
00:45:02,950 --> 00:44:43,920
the universality of life

1098
00:45:07,510 --> 00:45:05,670
all right hello my name is veronica and

1099
00:45:10,950 --> 00:45:07,520
i am going to talk to you all about a

1100
00:45:12,470 --> 00:45:10,960
new way of finding universality in life

1101
00:45:14,790 --> 00:45:12,480
to start we're all familiar with the

1102
00:45:16,550 --> 00:45:14,800
fact that life is very diverse on earth

1103
00:45:18,550 --> 00:45:16,560
and apart from a shared genetic code we

1104
00:45:20,550 --> 00:45:18,560
don't actually know what is common to

1105
00:45:21,829 --> 00:45:20,560
all instances of life

1106
00:45:23,670 --> 00:45:21,839
so that's a question i'm really

1107
00:45:27,430 --> 00:45:23,680
interested in what unites all life in

1108
00:45:29,270 --> 00:45:27,440
the universe regardless of environment

1109
00:45:31,030 --> 00:45:29,280
this is a useful question just because

1110
00:45:32,710 --> 00:45:31,040
it's interesting in itself but also

1111
00:45:34,230 --> 00:45:32,720
uncovering universal features of life

1112
00:45:36,230 --> 00:45:34,240
will help us in endeavors such as

1113
00:45:38,390 --> 00:45:36,240
constructing minimal life

1114
00:45:40,550 --> 00:45:38,400
constraining early models of or the

1115
00:45:43,829 --> 00:45:40,560
earliest life and searching for life

1116
00:45:46,150 --> 00:45:43,839
agnostically or weird life

1117
00:45:48,069 --> 00:45:46,160
so one way to find this universality is

1118
00:45:49,109 --> 00:45:48,079
to look at scaling patterns and if

1119
00:45:51,430 --> 00:45:49,119
you're not familiar with scaling

1120
00:45:53,750 --> 00:45:51,440
patterns all they are are how some

1121
00:45:55,430 --> 00:45:53,760
attribute changes as the system size

1122
00:45:57,589 --> 00:45:55,440
increases so you can have a linear

1123
00:45:59,349 --> 00:45:57,599
relationship but you can also have other

1124
00:46:01,670 --> 00:45:59,359
interesting ones such as sublinear or

1125
00:46:03,270 --> 00:46:01,680
super linear behavior

1126
00:46:05,030 --> 00:46:03,280
and throughout this presentation i will

1127
00:46:07,109 --> 00:46:05,040
demonstrate scaling relationships in the

1128
00:46:08,230 --> 00:46:07,119
way i just showed you as well as in log

1129
00:46:09,990 --> 00:46:08,240
space

1130
00:46:12,870 --> 00:46:10,000
where the slope denotes what scaling

1131
00:46:14,390 --> 00:46:12,880
behavior is so above one is super linear

1132
00:46:18,230 --> 00:46:14,400
below one is sub

1133
00:46:21,990 --> 00:46:19,510
the good news is that we've found

1134
00:46:24,390 --> 00:46:22,000
scaling in biology already so a very

1135
00:46:26,870 --> 00:46:24,400
common example is the metabolic rate of

1136
00:46:28,470 --> 00:46:26,880
animals where on this plot in the x-axis

1137
00:46:30,790 --> 00:46:28,480
you see body mass

1138
00:46:32,870 --> 00:46:30,800
and on the yc metabolic rate

1139
00:46:35,510 --> 00:46:32,880
and i wanted to

1140
00:46:37,670 --> 00:46:35,520
stress that it's very very strange that

1141
00:46:39,270 --> 00:46:37,680
so many of these diverse organisms fall

1142
00:46:41,190 --> 00:46:39,280
within this line

1143
00:46:42,710 --> 00:46:41,200
and what it's showing us is that with

1144
00:46:45,109 --> 00:46:42,720
all these organisms despite their

1145
00:46:47,109 --> 00:46:45,119
differences are all experiencing the

1146
00:46:49,270 --> 00:46:47,119
same universal constraints

1147
00:46:51,589 --> 00:46:49,280
so the reason we see this we learned

1148
00:46:53,190 --> 00:46:51,599
decades after this observation is that

1149
00:46:55,190 --> 00:46:53,200
there is a universality in

1150
00:46:57,829 --> 00:46:55,200
cardiovascular branching patterns that's

1151
00:46:59,109 --> 00:46:57,839
optimized for energy transport

1152
00:47:00,870 --> 00:46:59,119
in case you're not convinced that

1153
00:47:03,190 --> 00:47:00,880
scaling is very useful especially in the

1154
00:47:04,630 --> 00:47:03,200
purposes of astrobiology a quote from

1155
00:47:07,670 --> 00:47:04,640
jeffrey west who does research in this

1156
00:47:09,510 --> 00:47:07,680
work has a wonderful quote laid out if

1157
00:47:11,109 --> 00:47:09,520
you tell me the size of a mammal i can

1158
00:47:12,710 --> 00:47:11,119
use the scaling loss to tell you almost

1159
00:47:14,630 --> 00:47:12,720
everything about the average values of

1160
00:47:16,790 --> 00:47:14,640
its measurable characteristics so just

1161
00:47:18,470 --> 00:47:16,800
how much food it needs to eat each day

1162
00:47:20,549 --> 00:47:18,480
what its heart rate is

1163
00:47:22,870 --> 00:47:20,559
how long it will take to mature

1164
00:47:25,030 --> 00:47:22,880
the length and radius of its aorta

1165
00:47:27,430 --> 00:47:25,040
how many offspring you'll have

1166
00:47:29,430 --> 00:47:27,440
and so on and this is just knowing one

1167
00:47:31,670 --> 00:47:29,440
piece of information which is the size

1168
00:47:35,349 --> 00:47:31,680
and no other details so scaling laws

1169
00:47:36,950 --> 00:47:35,359
have immense predictive power

1170
00:47:39,349 --> 00:47:36,960
now what i want to do is find hidden

1171
00:47:41,190 --> 00:47:39,359
universality from biochemistry because

1172
00:47:42,630 --> 00:47:41,200
fewer studies have looked at that so

1173
00:47:44,309 --> 00:47:42,640
when we talk about size here what i'm

1174
00:47:46,790 --> 00:47:44,319
referring to is the size of an organism

1175
00:47:49,430 --> 00:47:46,800
or community's biochemical space or what

1176
00:47:51,270 --> 00:47:49,440
an organism is capable of biochemically

1177
00:47:53,190 --> 00:47:51,280
and an attribute what i'm interested is

1178
00:47:55,829 --> 00:47:53,200
is in the diversity of biochemical

1179
00:47:59,990 --> 00:47:57,270
and so what i'm showing here is pretty

1180
00:48:01,589 --> 00:48:00,000
abstract and one way to get about this

1181
00:48:03,349 --> 00:48:01,599
to make it more concrete is to look at

1182
00:48:05,349 --> 00:48:03,359
enzymes because they're a great proxy

1183
00:48:06,470 --> 00:48:05,359
for biochemical function they catalyze

1184
00:48:08,549 --> 00:48:06,480
most reactions

1185
00:48:10,630 --> 00:48:08,559
and along with that conveniently for us

1186
00:48:13,670 --> 00:48:10,640
they're classified by a four-digit ec

1187
00:48:15,510 --> 00:48:13,680
code that is related to its function

1188
00:48:17,190 --> 00:48:15,520
to break that down at the first digit we

1189
00:48:19,750 --> 00:48:17,200
have the broadest function for example

1190
00:48:21,190 --> 00:48:19,760
ec1 are the exceeda reductase enzymes

1191
00:48:24,390 --> 00:48:21,200
and there are any enzymes that transfer

1192
00:48:25,829 --> 00:48:24,400
electrons from one molecule to another

1193
00:48:27,510 --> 00:48:25,839
when we get to the second digit we're

1194
00:48:29,270 --> 00:48:27,520
adding more specificity we're saying

1195
00:48:32,069 --> 00:48:29,280
that these are oxidoreductases that use

1196
00:48:33,190 --> 00:48:32,079
choh groups as electron donors by the

1197
00:48:34,470 --> 00:48:33,200
third digit we're adding more

1198
00:48:36,630 --> 00:48:34,480
information we're specifying the

1199
00:48:38,230 --> 00:48:36,640
electron acceptor and by the time we get

1200
00:48:40,710 --> 00:48:38,240
to the fourth digit we're specifying the

1201
00:48:42,549 --> 00:48:40,720
exact enzyme so this is useful for us

1202
00:48:45,990 --> 00:48:42,559
because we can look at different

1203
00:48:47,430 --> 00:48:46,000
specificity levels of function

1204
00:48:49,030 --> 00:48:47,440
to give you a bird's eye view of all of

1205
00:48:51,510 --> 00:48:49,040
the broad functions all of the first

1206
00:48:52,870 --> 00:48:51,520
digit ecs we have the oxidoreductases as

1207
00:48:54,309 --> 00:48:52,880
we just mentioned

1208
00:48:55,829 --> 00:48:54,319
transferases which are enzymes that

1209
00:48:57,670 --> 00:48:55,839
transfer molecular groups from one

1210
00:48:59,829 --> 00:48:57,680
molecule to another

1211
00:49:01,430 --> 00:48:59,839
hydrolases which cleave molecular bonds

1212
00:49:03,750 --> 00:49:01,440
using hydrolysis

1213
00:49:05,670 --> 00:49:03,760
lyses which cleave bonds using any other

1214
00:49:08,710 --> 00:49:05,680
method besides hydrolysis

1215
00:49:13,109 --> 00:49:08,720
isomerases which shuffle molecules

1216
00:49:16,950 --> 00:49:15,030
so going back to this rather than saying

1217
00:49:18,470 --> 00:49:16,960
the size of biochemical space like what

1218
00:49:19,829 --> 00:49:18,480
does that actually mean

1219
00:49:21,750 --> 00:49:19,839
we can look at the total enzymes that

1220
00:49:23,109 --> 00:49:21,760
are encoded in a genome or metagenome

1221
00:49:24,230 --> 00:49:23,119
because that data is actually available

1222
00:49:25,910 --> 00:49:24,240
to us

1223
00:49:27,589 --> 00:49:25,920
and instead of saying diversity

1224
00:49:29,349 --> 00:49:27,599
biochemical functions we can talk about

1225
00:49:32,790 --> 00:49:29,359
the number of unique enzymes within a

1226
00:49:37,349 --> 00:49:34,870
so in the past we asked if enzyme

1227
00:49:39,589 --> 00:49:37,359
diversity scales across the domains and

1228
00:49:41,589 --> 00:49:39,599
across levels of biological organization

1229
00:49:43,750 --> 00:49:41,599
aka on the organism scale versus

1230
00:49:45,589 --> 00:49:43,760
ecosystem scale and we looked only at

1231
00:49:47,430 --> 00:49:45,599
the broad first digit ecs for this

1232
00:49:49,430 --> 00:49:47,440
question and we also want to know is

1233
00:49:51,270 --> 00:49:49,440
there universal behavior for all of

1234
00:49:52,710 --> 00:49:51,280
these biological groups because there's

1235
00:49:54,549 --> 00:49:52,720
no reason to suppose that there would be

1236
00:49:56,069 --> 00:49:54,559
such a relationship

1237
00:49:58,230 --> 00:49:56,079
the way we did this is we use the joint

1238
00:50:00,549 --> 00:49:58,240
genome institute or jgi which contains

1239
00:50:02,549 --> 00:50:00,559
thousands of genos and metagenomes

1240
00:50:04,790 --> 00:50:02,559
and they're lovely because they have a

1241
00:50:06,870 --> 00:50:04,800
pipeline to annotate these genomes and

1242
00:50:09,349 --> 00:50:06,880
infer what enzymes are present and from

1243
00:50:11,510 --> 00:50:09,359
there they have ec codes tacked onto it

1244
00:50:13,430 --> 00:50:11,520
nice way to organize our data

1245
00:50:15,270 --> 00:50:13,440
and with our data set post filtering to

1246
00:50:17,829 --> 00:50:15,280
make sure we have high quality data we

1247
00:50:19,190 --> 00:50:17,839
have hundreds of thousands of samples

1248
00:50:22,150 --> 00:50:19,200
which is enough for us to make some

1249
00:50:24,309 --> 00:50:22,160
statistical generalizations

1250
00:50:26,470 --> 00:50:24,319
so good news scaling does exist at the

1251
00:50:28,870 --> 00:50:26,480
broadest first digit ec function and we

1252
00:50:31,030 --> 00:50:28,880
showed that in our most recent paper so

1253
00:50:32,549 --> 00:50:31,040
what you're looking at here is

1254
00:50:34,309 --> 00:50:32,559
all of the scaling relationships for the

1255
00:50:36,150 --> 00:50:34,319
first digit and if we're looking

1256
00:50:38,630 --> 00:50:36,160
specifically at one data point that

1257
00:50:40,950 --> 00:50:38,640
represents a genome and on the x-axis

1258
00:50:42,950 --> 00:50:40,960
that's the total biochemical toolkit and

1259
00:50:45,990 --> 00:50:42,960
on the y-axis we have how many unique

1260
00:50:48,150 --> 00:50:46,000
enzymes are within that particular class

1261
00:50:50,069 --> 00:50:48,160
and also there is universality for a lot

1262
00:50:52,150 --> 00:50:50,079
of these ecs so for example with the

1263
00:50:53,990 --> 00:50:52,160
axial reductases it's super linear

1264
00:50:55,750 --> 00:50:54,000
whether you're talking about bacteria

1265
00:50:59,829 --> 00:50:55,760
archaea or the metagenome which

1266
00:51:01,910 --> 00:50:59,839
represents a large scale ecosystem

1267
00:51:03,270 --> 00:51:01,920
and here what i'm showing are the slopes

1268
00:51:04,870 --> 00:51:03,280
of the trend lines that i just showed

1269
00:51:06,470 --> 00:51:04,880
you in the previous plot and the

1270
00:51:08,630 --> 00:51:06,480
universality comes from the fact that

1271
00:51:10,710 --> 00:51:08,640
within a given row we have the same

1272
00:51:12,870 --> 00:51:10,720
color across the board now you'll notice

1273
00:51:14,390 --> 00:51:12,880
that with the lyses and the asom races

1274
00:51:17,589 --> 00:51:14,400
they're not demonstrating that universal

1275
00:51:19,990 --> 00:51:17,599
behavior and i have some ideas as to why

1276
00:51:21,670 --> 00:51:20,000
so with the ec system that was made for

1277
00:51:24,230 --> 00:51:21,680
biochemists to do traditional

1278
00:51:25,910 --> 00:51:24,240
biochemistry but what we're after is to

1279
00:51:28,230 --> 00:51:25,920
look at a more abstract sense of

1280
00:51:30,710 --> 00:51:28,240
function so if we combine hydrolases and

1281
00:51:32,710 --> 00:51:30,720
lyses which are enzymes that both cleave

1282
00:51:34,390 --> 00:51:32,720
molecular bonds then we see that

1283
00:51:36,870 --> 00:51:34,400
universal behavior and happens to be

1284
00:51:38,790 --> 00:51:36,880
super linear isomerase is still not

1285
00:51:41,349 --> 00:51:38,800
universal but i suspect that's because

1286
00:51:42,710 --> 00:51:41,359
those enzymes act out on one molecule

1287
00:51:44,870 --> 00:51:42,720
and typically you'll have things like

1288
00:51:46,230 --> 00:51:44,880
intramolecular oxide reductase reactions

1289
00:51:49,030 --> 00:51:46,240
in them which i think makes that more of

1290
00:51:51,270 --> 00:51:49,040
a mixed bag category

1291
00:51:52,870 --> 00:51:51,280
so currently what i'm after is i want to

1292
00:51:55,190 --> 00:51:52,880
see if there's scaling behavior for the

1293
00:51:57,190 --> 00:51:55,200
more specific ecs the second and third

1294
00:51:59,270 --> 00:51:57,200
digits i also want to know if that

1295
00:52:01,670 --> 00:51:59,280
scaling is universal as you look down at

1296
00:52:03,349 --> 00:52:01,680
levels of specificity

1297
00:52:05,510 --> 00:52:03,359
and finally i want to see to what extent

1298
00:52:07,270 --> 00:52:05,520
scaling laws hold in deep time and i

1299
00:52:09,030 --> 00:52:07,280
want to see if the scaling coefficients

1300
00:52:11,190 --> 00:52:09,040
or the slopes are correlated with

1301
00:52:12,630 --> 00:52:11,200
phylogenetic distances the idea being

1302
00:52:15,510 --> 00:52:12,640
that if you're more closely related to

1303
00:52:17,589 --> 00:52:15,520
one organism you'd have a similar slope

1304
00:52:19,510 --> 00:52:17,599
to that organism

1305
00:52:21,750 --> 00:52:19,520
so looking at this first question uh

1306
00:52:24,309 --> 00:52:21,760
good news again scaling does exist at

1307
00:52:26,470 --> 00:52:24,319
the second and third digit level so what

1308
00:52:28,390 --> 00:52:26,480
you're seeing here are oxy reductases

1309
00:52:29,910 --> 00:52:28,400
across levels of specificity and these

1310
00:52:30,950 --> 00:52:29,920
all happen to demonstrate super linear

1311
00:52:32,870 --> 00:52:30,960
behavior

1312
00:52:34,870 --> 00:52:32,880
interesting

1313
00:52:36,870 --> 00:52:34,880
the same is true for ligases these

1314
00:52:39,190 --> 00:52:36,880
ligases all demonstrate sublinear

1315
00:52:41,030 --> 00:52:39,200
behavior

1316
00:52:43,109 --> 00:52:41,040
now is it the case that it's universal

1317
00:52:45,109 --> 00:52:43,119
across levels of specificity all of the

1318
00:52:47,589 --> 00:52:45,119
time

1319
00:52:49,430 --> 00:52:47,599
not really so that is not always the

1320
00:52:52,230 --> 00:52:49,440
case for example with the transferases

1321
00:52:53,670 --> 00:52:52,240
ec2 that demonstrates sublinear behavior

1322
00:52:55,430 --> 00:52:53,680
but when we look at the second digit

1323
00:52:57,430 --> 00:52:55,440
then we see more of a mixed bag of

1324
00:53:00,230 --> 00:52:57,440
different sublinear linear and super

1325
00:53:01,670 --> 00:53:00,240
linear behavior

1326
00:53:03,109 --> 00:53:01,680
now finally is there a correlation

1327
00:53:05,030 --> 00:53:03,119
between scaling coefficients and

1328
00:53:07,670 --> 00:53:05,040
phylogenetic distance

1329
00:53:09,750 --> 00:53:07,680
what we found when we examined these

1330
00:53:11,670 --> 00:53:09,760
slopes at the phylum level is that there

1331
00:53:13,349 --> 00:53:11,680
are differences in these scaling slopes

1332
00:53:15,270 --> 00:53:13,359
so what you're looking at here are

1333
00:53:17,910 --> 00:53:15,280
different phyla bacteria

1334
00:53:19,510 --> 00:53:17,920
across these different ecs and plotted

1335
00:53:21,190 --> 00:53:19,520
here on the lines are the slopes and

1336
00:53:22,390 --> 00:53:21,200
their confidence intervals so you can

1337
00:53:24,630 --> 00:53:22,400
see there are differences and not

1338
00:53:26,790 --> 00:53:24,640
surprisingly the oxial reductases have

1339
00:53:29,190 --> 00:53:26,800
slopes above one the transferases

1340
00:53:31,829 --> 00:53:29,200
typically are slopes below one

1341
00:53:33,750 --> 00:53:31,839
but the point is that they're different

1342
00:53:35,670 --> 00:53:33,760
but they're not necessarily correlated

1343
00:53:38,470 --> 00:53:35,680
with phylogenetic distance so this is a

1344
00:53:40,870 --> 00:53:38,480
tree representing bacterial orders

1345
00:53:42,790 --> 00:53:40,880
and these colors on the grid plot

1346
00:53:45,270 --> 00:53:42,800
represent the scaling slope so you'd

1347
00:53:46,950 --> 00:53:45,280
expect there to be more similar colors

1348
00:53:49,270 --> 00:53:46,960
uh clustered together if there was a

1349
00:53:50,630 --> 00:53:49,280
correlation but that's not looking like

1350
00:53:51,990 --> 00:53:50,640
that's the case

1351
00:53:53,430 --> 00:53:52,000
we're going to perform more statistical

1352
00:53:55,750 --> 00:53:53,440
analyses to

1353
00:53:57,750 --> 00:53:55,760
make that result more robust so if it's

1354
00:53:59,190 --> 00:53:57,760
not correlated but there are differences

1355
00:54:01,750 --> 00:53:59,200
then could it be the case that the

1356
00:54:04,710 --> 00:54:01,760
random partitioning of taxa into

1357
00:54:06,309 --> 00:54:04,720
different groups is you know what leads

1358
00:54:08,630 --> 00:54:06,319
to these scaling slopes in other words

1359
00:54:11,510 --> 00:54:08,640
if we randomize what taxon is in which

1360
00:54:12,390 --> 00:54:11,520
group will we still see the same thing

1361
00:54:14,390 --> 00:54:12,400
uh

1362
00:54:16,150 --> 00:54:14,400
the answer is we don't quite know yet

1363
00:54:17,990 --> 00:54:16,160
but i do want to illustrate what i mean

1364
00:54:19,670 --> 00:54:18,000
by this idea

1365
00:54:22,069 --> 00:54:19,680
currently i'm running these permutation

1366
00:54:24,309 --> 00:54:22,079
tests basically mixing up which taxon

1367
00:54:26,230 --> 00:54:24,319
goes where and the idea is if the

1368
00:54:28,950 --> 00:54:26,240
standard deviation of our true data

1369
00:54:30,870 --> 00:54:28,960
happens to lie outside of the permutated

1370
00:54:32,790 --> 00:54:30,880
standard deviations then we can say with

1371
00:54:35,670 --> 00:54:32,800
some degree of confidence that it's not

1372
00:54:37,349 --> 00:54:35,680
the result of just random partitioning

1373
00:54:38,630 --> 00:54:37,359
and if that's true then that makes it

1374
00:54:40,309 --> 00:54:38,640
more interesting because there might be

1375
00:54:42,710 --> 00:54:40,319
some physical reason at play that we

1376
00:54:44,710 --> 00:54:42,720
just don't know about

1377
00:54:46,230 --> 00:54:44,720
okay so summary of all the questions

1378
00:54:48,069 --> 00:54:46,240
answers so far

1379
00:54:49,190 --> 00:54:48,079
and my future goals are to investigate

1380
00:54:51,109 --> 00:54:49,200
why there are differences in these

1381
00:54:52,309 --> 00:54:51,119
scaling slopes

1382
00:54:54,150 --> 00:54:52,319
i also want to know what specific

1383
00:54:55,829 --> 00:54:54,160
biochemical functions drive the first

1384
00:54:57,589 --> 00:54:55,839
digit scaling because i think that'll

1385
00:54:58,230 --> 00:54:57,599
give some hint as to what the mechanism

1386
00:55:02,390 --> 00:54:58,240
is

1387
00:55:03,829 --> 00:55:02,400
universality in the first place

1388
00:55:06,069 --> 00:55:03,839
and i also want to control for sampling

1389
00:55:07,910 --> 00:55:06,079
bias in the phyla so it's not uncommon

1390
00:55:09,510 --> 00:55:07,920
for a given phylum to have thousands of

1391
00:55:11,910 --> 00:55:09,520
samples whereas another one might have

1392
00:55:14,069 --> 00:55:11,920
50. so in order to make this more robust

1393
00:55:16,150 --> 00:55:14,079
i want to make sure that all phyla are

1394
00:55:17,750 --> 00:55:16,160
evenly sampled

1395
00:55:19,190 --> 00:55:17,760
so going back to these goals that i

1396
00:55:21,109 --> 00:55:19,200
mentioned earlier

1397
00:55:23,270 --> 00:55:21,119
i believe that universal scaling and

1398
00:55:26,549 --> 00:55:23,280
function can aid in these endeavors and

1399
00:55:28,309 --> 00:55:26,559
particularly with luca we can infer how

1400
00:55:30,710 --> 00:55:28,319
many enzymes might have been present in

1401
00:55:32,549 --> 00:55:30,720
this system and using these scaling laws

1402
00:55:34,710 --> 00:55:32,559
we can actually determine what ratios of

1403
00:55:37,270 --> 00:55:34,720
functions we would expect and along with

1404
00:55:39,109 --> 00:55:37,280
that for searching for life agnostically

1405
00:55:40,789 --> 00:55:39,119
we're talking about function here and

1406
00:55:42,470 --> 00:55:40,799
that means that we can substitute

1407
00:55:44,150 --> 00:55:42,480
compounds and we can think about

1408
00:55:45,750 --> 00:55:44,160
alternative biochemistries to make our

1409
00:55:48,150 --> 00:55:45,760
search for life

1410
00:55:50,230 --> 00:55:48,160
elsewhere in the universe a little more

1411
00:55:52,390 --> 00:55:50,240
open-minded

1412
00:55:54,230 --> 00:55:52,400
so big thank you to the e-life team and

1413
00:55:56,150 --> 00:55:54,240
for our collaborators and thank you all

1414
00:56:05,270 --> 00:55:56,160
for being here and listening

1415
00:56:08,789 --> 00:56:07,589
hi i'm vladimir subotin university of

1416
00:56:11,270 --> 00:56:08,799
this country

1417
00:56:12,470 --> 00:56:11,280
now when you showed this graph

1418
00:56:18,309 --> 00:56:12,480
that uh

1419
00:56:22,390 --> 00:56:20,230
oh yes

1420
00:56:24,910 --> 00:56:22,400
uh i wonder uh

1421
00:56:26,789 --> 00:56:24,920
that you restricted this uh

1422
00:56:27,990 --> 00:56:26,799
representation

1423
00:56:35,589 --> 00:56:28,000
only

1424
00:56:37,190 --> 00:56:35,599
mammals but particular to placental

1425
00:56:40,069 --> 00:56:37,200
mammals

1426
00:56:41,349 --> 00:56:40,079
and what about other tax for example

1427
00:56:44,390 --> 00:56:41,359
what

1428
00:56:46,309 --> 00:56:44,400
jellyfish or octopus yeah for sure yeah

1429
00:56:47,670 --> 00:56:46,319
so fortunately other scholars have

1430
00:56:50,630 --> 00:56:47,680
investigated this question and have

1431
00:56:52,470 --> 00:56:50,640
looked at all life so there is a plot

1432
00:56:55,430 --> 00:56:52,480
that exists that includes things like

1433
00:56:57,670 --> 00:56:55,440
prokaryotes and non-placental mammals

1434
00:56:59,589 --> 00:56:57,680
i just chose this plot for simplicity to

1435
00:57:01,589 --> 00:56:59,599
illustrate this idea that you can have

1436
00:57:03,589 --> 00:57:01,599
really despair organisms that fall

1437
00:57:06,549 --> 00:57:03,599
within this universal line

1438
00:57:06,559 --> 00:57:09,750
hi oh love it

1439
00:57:12,630 --> 00:57:11,349
we just have some questions in the chat

1440
00:57:14,150 --> 00:57:12,640
oh

1441
00:57:17,910 --> 00:57:14,160
um

1442
00:57:18,710 --> 00:57:17,920
a question from joanna monte meisel

1443
00:57:20,710 --> 00:57:18,720
how

1444
00:57:24,710 --> 00:57:20,720
does this compare to the scaling laws

1445
00:57:29,750 --> 00:57:27,109
subscribing yeah

1446
00:57:32,789 --> 00:57:29,760
the chat keeps moving uh

1447
00:57:34,549 --> 00:57:32,799
by molina and why one minute

1448
00:57:36,710 --> 00:57:34,559
do i have this correct that you are

1449
00:57:39,270 --> 00:57:36,720
getting differences among phyla in

1450
00:57:41,510 --> 00:57:39,280
enzymes whereas they fail to find them

1451
00:57:44,309 --> 00:57:41,520
in other gene types such as

1452
00:57:48,580 --> 00:57:44,319
transcriptional regulators

1453
00:58:05,190 --> 00:57:57,210
[Music]

1454
00:58:05,200 --> 00:58:13,349
i don't think this is working anymore

1455
00:58:17,430 --> 00:58:15,270
yeah that's a really great question i'm

1456
00:58:19,990 --> 00:58:17,440
actually not familiar with that

1457
00:58:21,990 --> 00:58:20,000
particular study uh but i will look into

1458
00:58:23,910 --> 00:58:22,000
that and get back to you if possible

1459
00:58:25,510 --> 00:58:23,920
that's really interesting uh because so

1460
00:58:27,750 --> 00:58:25,520
far we've only looked at genomes and we

1461
00:58:29,190 --> 00:58:27,760
haven't looked at um transcription data

1462
00:58:30,789 --> 00:58:29,200
yet

1463
00:58:32,870 --> 00:58:30,799
and uh really quick one more question

1464
00:58:35,030 --> 00:58:32,880
from the audience

1465
00:58:36,549 --> 00:58:35,040
so great talk just have a

1466
00:58:37,829 --> 00:58:36,559
kind of a quick question related to

1467
00:58:39,990 --> 00:58:37,839
transcription i know i haven't looked at

1468
00:58:42,549 --> 00:58:40,000
it yet but you can kind of do a census

1469
00:58:44,230 --> 00:58:42,559
of enzymes and presence but they not may

1470
00:58:46,390 --> 00:58:44,240
not necessarily be part of functional

1471
00:58:48,309 --> 00:58:46,400
pathways particularly in some archaean

1472
00:58:49,990 --> 00:58:48,319
bacteria so i'm wondering if you've

1473
00:58:51,430 --> 00:58:50,000
looked at complete pathways and if the

1474
00:58:52,710 --> 00:58:51,440
scaling patterns

1475
00:58:55,030 --> 00:58:52,720
remain in some of those complete

1476
00:58:57,430 --> 00:58:55,040
pathways rather than just in individual

1477
00:58:59,190 --> 00:58:57,440
ec classified numbers

1478
00:59:03,270 --> 00:58:59,200
okay it was a little bit hard to hear

1479
00:59:07,349 --> 00:59:04,390
we don't necessarily

1480
00:59:08,789 --> 00:59:07,359
know if those enzymes are expressed um

1481
00:59:10,549 --> 00:59:08,799
and that that is a shortcoming of the

1482
00:59:12,309 --> 00:59:10,559
study right so there is far more

1483
00:59:14,630 --> 00:59:12,319
metagenomes and genomes available than

1484
00:59:17,270 --> 00:59:14,640
transcriptomic data uh and the

1485
00:59:18,630 --> 00:59:17,280
transcriptonomic data that does exist is

1486
00:59:21,349 --> 00:59:18,640
at least in jgi is usually the

1487
00:59:22,549 --> 00:59:21,359
metagenomic data whereas for this study

1488
00:59:23,910 --> 00:59:22,559
that i'm currently working on i'm

1489
00:59:26,230 --> 00:59:23,920
interested in the more individual

1490
00:59:28,230 --> 00:59:26,240
organisms like archaea and bacteria

1491
00:59:30,829 --> 00:59:28,240
but if you know of data sources that

1492
00:59:33,510 --> 00:59:30,839
have such data please let me

1493
00:59:35,600 --> 00:59:33,520
know thank you

1494
00:59:41,750 --> 00:59:35,610
all right thank you okay thanks

1495
00:59:47,190 --> 00:59:43,270
so next we have

1496
00:59:51,589 --> 00:59:49,190
for an evolutionary perspective on

1497
00:59:53,510 --> 00:59:51,599
prions trends and function of prion

1498
01:00:13,190 --> 00:59:53,520
candidates across all three domains of

1499
01:00:17,349 --> 01:00:15,829
so at 12 minutes i'll just like

1500
01:00:18,630 --> 01:00:17,359
gesture and i'll give you three minutes

1501
01:00:20,230 --> 01:00:18,640
for questions

1502
01:00:22,309 --> 01:00:20,240
but i'll let you wrap up your thoughts

1503
01:00:25,190 --> 01:00:22,319
and go into that time

1504
01:00:28,789 --> 01:00:27,190
thank you so much for coming my name is

1505
01:00:31,349 --> 01:00:28,799
thomas zaykovsky

1506
01:00:32,950 --> 01:00:31,359
i'm a neurobiologist fascinated with the

1507
01:00:35,510 --> 01:00:32,960
early evolution

1508
01:00:37,349 --> 01:00:35,520
and i'm working at nasa ames with lynn

1509
01:00:39,430 --> 01:00:37,359
rothschild

1510
01:00:42,150 --> 01:00:39,440
today i'd like to share with you a

1511
01:00:44,069 --> 01:00:42,160
radical idea that i that came to my mind

1512
01:00:46,789 --> 01:00:44,079
during my phd

1513
01:00:49,190 --> 01:00:46,799
an idea that an aggregate discovered in

1514
01:00:50,710 --> 01:00:49,200
human brain could be a relic of early

1515
01:00:53,510 --> 01:00:50,720
evolution

1516
01:00:55,190 --> 01:00:53,520
so in my research i focus on pre-ends

1517
01:00:56,870 --> 01:00:55,200
preamps are fascinating because they're

1518
01:00:58,710 --> 01:00:56,880
so controversial

1519
01:01:01,430 --> 01:00:58,720
let me give you an example

1520
01:01:04,309 --> 01:01:01,440
prions were first discovered as a

1521
01:01:08,230 --> 01:01:04,319
protein aggregates in patients suffering

1522
01:01:09,430 --> 01:01:08,240
from infectious brain disorders

1523
01:01:11,430 --> 01:01:09,440
but first

1524
01:01:13,670 --> 01:01:11,440
koreans were thought to be viruses i

1525
01:01:16,390 --> 01:01:13,680
mean those disorders were thought to be

1526
01:01:17,670 --> 01:01:16,400
caused by viruses it took decades to

1527
01:01:20,309 --> 01:01:17,680
accept the

1528
01:01:21,910 --> 01:01:20,319
controversial idea that the protein

1529
01:01:23,510 --> 01:01:21,920
itself could carry biological

1530
01:01:26,549 --> 01:01:23,520
information

1531
01:01:27,589 --> 01:01:26,559
from an organism to another eventually

1532
01:01:29,990 --> 01:01:27,599
causing

1533
01:01:33,109 --> 01:01:30,000
a disease

1534
01:01:35,950 --> 01:01:33,119
so for the first 20 maybe 30 years

1535
01:01:38,549 --> 01:01:35,960
springs were widely

1536
01:01:40,870 --> 01:01:38,559
recognizable as

1537
01:01:42,309 --> 01:01:40,880
infectious proteins but recently we have

1538
01:01:44,630 --> 01:01:42,319
experienced dramatic shift in

1539
01:01:46,630 --> 01:01:44,640
perspective on prunes

1540
01:01:48,870 --> 01:01:46,640
maybe even to the extent that the name

1541
01:01:50,549 --> 01:01:48,880
itself no longer gives the justice to

1542
01:01:53,349 --> 01:01:50,559
the phenomenon

1543
01:01:56,309 --> 01:01:53,359
the name prion was invented to reflect

1544
01:01:59,829 --> 01:01:56,319
infectious nature of proteins it is an

1545
01:02:00,870 --> 01:01:59,839
acronym for protein nauseous infectious

1546
01:02:04,150 --> 01:02:00,880
particle

1547
01:02:07,430 --> 01:02:04,160
but in recent years we have found

1548
01:02:09,589 --> 01:02:07,440
uh not only prions in mammals but many

1549
01:02:12,390 --> 01:02:09,599
other organisms including bacteria

1550
01:02:15,270 --> 01:02:12,400
archaea and even viruses

1551
01:02:17,910 --> 01:02:15,280
so and since the term infection is

1552
01:02:20,309 --> 01:02:17,920
reserved for invasion and growth of

1553
01:02:24,069 --> 01:02:20,319
germs in a body the name itself no

1554
01:02:25,910 --> 01:02:24,079
longer properly describes the phenomena

1555
01:02:28,069 --> 01:02:25,920
so it was

1556
01:02:29,829 --> 01:02:28,079
if that wasn't enough prions uh were

1557
01:02:30,870 --> 01:02:29,839
recently found to play beneficial

1558
01:02:33,910 --> 01:02:30,880
functions

1559
01:02:35,029 --> 01:02:33,920
both in human and microorganisms

1560
01:02:37,270 --> 01:02:35,039
in yeast

1561
01:02:39,029 --> 01:02:37,280
prunes can facilitate rapid adaptation

1562
01:02:41,990 --> 01:02:39,039
to changing environment

1563
01:02:43,990 --> 01:02:42,000
and there are a powerful epigenetic

1564
01:02:46,309 --> 01:02:44,000
mechanism of adaptation

1565
01:02:49,910 --> 01:02:46,319
that likely existed more than one

1566
01:02:51,990 --> 01:02:49,920
billion years ago when these two species

1567
01:02:53,750 --> 01:02:52,000
diverged

1568
01:02:55,750 --> 01:02:53,760
in fact some

1569
01:02:57,029 --> 01:02:55,760
researchers are so impressed by the new

1570
01:02:59,109 --> 01:02:57,039
perspective

1571
01:03:00,829 --> 01:02:59,119
that they call it the largest paradigm

1572
01:03:03,510 --> 01:03:00,839
shifts

1573
01:03:06,309 --> 01:03:03,520
since identification of dna is a

1574
01:03:08,710 --> 01:03:06,319
molecule of heredity pretty bold

1575
01:03:10,630 --> 01:03:08,720
uh in a paper that we published last

1576
01:03:12,789 --> 01:03:10,640
year we have found

1577
01:03:13,990 --> 01:03:12,799
uh that candidate prion proteins from

1578
01:03:15,670 --> 01:03:14,000
archaea

1579
01:03:18,630 --> 01:03:15,680
can uh transmit

1580
01:03:20,870 --> 01:03:18,640
phenotypes for many generations when

1581
01:03:23,349 --> 01:03:20,880
expressed in modal organisms

1582
01:03:25,430 --> 01:03:23,359
the motivation for this paper was to

1583
01:03:27,670 --> 01:03:25,440
search for pre and specifically in the

1584
01:03:29,349 --> 01:03:27,680
domain archaea because it was the last

1585
01:03:31,910 --> 01:03:29,359
domain of life

1586
01:03:33,430 --> 01:03:31,920
not studied in regards to prince at the

1587
01:03:34,390 --> 01:03:33,440
time

1588
01:03:37,750 --> 01:03:34,400
and

1589
01:03:39,910 --> 01:03:37,760
with this work

1590
01:03:42,230 --> 01:03:39,920
uh we have helped to close the gap in

1591
01:03:44,230 --> 01:03:42,240
understanding how widespread

1592
01:03:46,390 --> 01:03:44,240
the prion phenomenon is on the

1593
01:03:48,710 --> 01:03:46,400
evolutionary tree of life

1594
01:03:50,789 --> 01:03:48,720
and it was the first step to start

1595
01:03:53,990 --> 01:03:50,799
asking questions about the origin of

1596
01:03:58,150 --> 01:03:54,000
prions so climbing the evolutionary tree

1597
01:03:59,349 --> 01:03:58,160
uh of life downward

1598
01:04:02,549 --> 01:03:59,359
uh

1599
01:04:04,870 --> 01:04:02,559
so could it be that prion aggregation

1600
01:04:07,349 --> 01:04:04,880
or protein

1601
01:04:11,190 --> 01:04:07,359
aggregates capable of storing biological

1602
01:04:14,150 --> 01:04:11,200
information exists on early earth

1603
01:04:16,470 --> 01:04:14,160
could they be forming abiotically

1604
01:04:18,630 --> 01:04:16,480
what roles could these aggregates have

1605
01:04:20,710 --> 01:04:18,640
in early life or maybe could they even

1606
01:04:24,829 --> 01:04:20,720
facilitate the origin of life these are

1607
01:04:27,510 --> 01:04:24,839
the major questions that motivate my

1608
01:04:29,670 --> 01:04:27,520
research uh to understand the potential

1609
01:04:31,589 --> 01:04:29,680
functions of the oldest prions on earth

1610
01:04:33,270 --> 01:04:31,599
let's spend a little bit of time looking

1611
01:04:37,670 --> 01:04:33,280
at how they work in contemporary

1612
01:04:40,230 --> 01:04:37,680
organisms so on this animation

1613
01:04:43,109 --> 01:04:40,240
you can see a pre and protein in its

1614
01:04:45,829 --> 01:04:43,119
native soluble state and like all pre

1615
01:04:47,270 --> 01:04:45,839
and proteins it can misfold another term

1616
01:04:49,910 --> 01:04:47,280
from medicine

1617
01:04:52,710 --> 01:04:49,920
actually more adequately we should say

1618
01:04:55,109 --> 01:04:52,720
it obtains an alternative fold it

1619
01:04:57,029 --> 01:04:55,119
changes its confirmation increasing its

1620
01:05:00,470 --> 01:04:57,039
beta sheet content

1621
01:05:03,430 --> 01:05:00,480
in this form it can start force other

1622
01:05:04,710 --> 01:05:03,440
copies of itself to do the same

1623
01:05:07,029 --> 01:05:04,720
and

1624
01:05:08,630 --> 01:05:07,039
in this stage these proteins can adhere

1625
01:05:11,349 --> 01:05:08,640
to each other

1626
01:05:14,470 --> 01:05:11,359
forming a very tight interactions

1627
01:05:16,230 --> 01:05:14,480
and in consequence forming an insoluble

1628
01:05:21,109 --> 01:05:16,240
amyloid fiber

1629
01:05:22,630 --> 01:05:21,119
is very rigid it

1630
01:05:25,510 --> 01:05:22,640
is resistant to high range of

1631
01:05:27,829 --> 01:05:25,520
temperatures ph and even degradation and

1632
01:05:30,309 --> 01:05:27,839
importantly amyloids can be made out of

1633
01:05:31,510 --> 01:05:30,319
very short peptides even prebiotically

1634
01:05:33,990 --> 01:05:31,520
possible

1635
01:05:36,630 --> 01:05:34,000
so it's likely that amyloids existed on

1636
01:05:39,270 --> 01:05:36,640
early earth

1637
01:05:41,430 --> 01:05:39,280
importantly amyloid

1638
01:05:43,750 --> 01:05:41,440
grows exponentially fast

1639
01:05:46,390 --> 01:05:43,760
at first there is a lag phase but then

1640
01:05:48,710 --> 01:05:46,400
it grows exponentially quick

1641
01:05:50,870 --> 01:05:48,720
and it quickly leads to depletion of

1642
01:05:53,430 --> 01:05:50,880
native natively folded versions of the

1643
01:05:55,670 --> 01:05:53,440
protein that builds it so

1644
01:05:57,589 --> 01:05:55,680
pre-owned proteins that have amyloid

1645
01:05:58,549 --> 01:05:57,599
fold in it

1646
01:06:01,029 --> 01:05:58,559
these

1647
01:06:03,670 --> 01:06:01,039
prion proteins aggregates in the form of

1648
01:06:05,349 --> 01:06:03,680
amyloid are often unable to perform

1649
01:06:06,950 --> 01:06:05,359
their functions that they had before

1650
01:06:09,990 --> 01:06:06,960
they aggregated

1651
01:06:12,390 --> 01:06:10,000
so if that happens in a microorganism

1652
01:06:13,430 --> 01:06:12,400
phenotypically it looks like the gene

1653
01:06:16,309 --> 01:06:13,440
deletion

1654
01:06:19,430 --> 01:06:16,319
but in fact the gene is not affected

1655
01:06:21,589 --> 01:06:19,440
therefore the change in the phenotype

1656
01:06:23,270 --> 01:06:21,599
uh yeah it depends on the protein

1657
01:06:28,390 --> 01:06:23,280
aggregation and it's shared

1658
01:06:31,589 --> 01:06:30,230
and just like in case of chromatin

1659
01:06:34,069 --> 01:06:31,599
epigenetics

1660
01:06:37,430 --> 01:06:34,079
the trait can be heritable because the

1661
01:06:39,190 --> 01:06:37,440
aggregate can be passed to daughter cell

1662
01:06:41,589 --> 01:06:39,200
and continue recruiting freshly

1663
01:06:44,230 --> 01:06:41,599
synthesized copies of the same protein

1664
01:06:46,630 --> 01:06:44,240
to the growing amyloid rendering the

1665
01:06:48,390 --> 01:06:46,640
protein unable to perform its functions

1666
01:06:50,470 --> 01:06:48,400
for many generations

1667
01:06:52,710 --> 01:06:50,480
if the abyloid aggregate can be passed

1668
01:06:55,990 --> 01:06:52,720
to another generation of cells this is

1669
01:06:58,829 --> 01:06:56,000
what we call prion so in this

1670
01:07:01,270 --> 01:06:58,839
sense prion is a heritable aggregate or

1671
01:07:03,750 --> 01:07:01,280
condensate that can change cellular

1672
01:07:07,349 --> 01:07:03,760
phenotypes for generations in case of

1673
01:07:09,430 --> 01:07:07,359
classical east prion protein sup 35

1674
01:07:12,150 --> 01:07:09,440
the switch to amyloid promoting state

1675
01:07:14,069 --> 01:07:12,160
happens every 1 million divisions and is

1676
01:07:15,910 --> 01:07:14,079
stable for a thousand generations for

1677
01:07:18,150 --> 01:07:15,920
ten thousand generations

1678
01:07:19,349 --> 01:07:18,160
in other words prion behave as molecular

1679
01:07:20,549 --> 01:07:19,359
switches

1680
01:07:23,750 --> 01:07:20,559
uh

1681
01:07:26,789 --> 01:07:23,760
they can broaden phenotypic diversity

1682
01:07:29,990 --> 01:07:26,799
and paraphrasing adriana guzi having a

1683
01:07:32,150 --> 01:07:30,000
protein that can exist an on and off

1684
01:07:34,870 --> 01:07:32,160
state where one of the states is

1685
01:07:36,870 --> 01:07:34,880
heritable is a wonderful way to transmit

1686
01:07:39,029 --> 01:07:36,880
information and it would be surprising

1687
01:07:41,589 --> 01:07:39,039
if nature didn't utilize it for

1688
01:07:43,829 --> 01:07:41,599
the system in order to solve specific

1689
01:07:45,829 --> 01:07:43,839
problems during evolution

1690
01:07:49,029 --> 01:07:45,839
and here are some examples how yeast can

1691
01:07:51,670 --> 01:07:49,039
benefit from prions on the top left part

1692
01:07:53,670 --> 01:07:51,680
you can see the prion gar plus

1693
01:07:56,069 --> 01:07:53,680
the rate of garplast formation can be

1694
01:07:58,309 --> 01:07:56,079
influenced by lactic acid and in

1695
01:08:00,870 --> 01:07:58,319
consequence enabling yeast to use

1696
01:08:03,430 --> 01:08:00,880
various carbon sources

1697
01:08:04,870 --> 01:08:03,440
switching from metabolic specialists to

1698
01:08:07,190 --> 01:08:04,880
generalists

1699
01:08:09,829 --> 01:08:07,200
other consequences of pre-information

1700
01:08:12,230 --> 01:08:09,839
include switching to

1701
01:08:14,870 --> 01:08:12,240
increasing sporulation or even

1702
01:08:17,829 --> 01:08:14,880
expressing subtelomeric regions which is

1703
01:08:21,189 --> 01:08:17,839
an example how prion mechanism regulates

1704
01:08:23,669 --> 01:08:21,199
another epigenetic mechanism

1705
01:08:26,229 --> 01:08:23,679
my personally favorite

1706
01:08:29,590 --> 01:08:26,239
example is prion

1707
01:08:30,470 --> 01:08:29,600
psi plus made of scp-35 protein that i

1708
01:08:32,229 --> 01:08:30,480
mentioned

1709
01:08:34,630 --> 01:08:32,239
on the previous slide it's

1710
01:08:35,990 --> 01:08:34,640
formation allows to read through

1711
01:08:39,829 --> 01:08:36,000
stop codons

1712
01:08:41,669 --> 01:08:39,839
it uncovers hidden genetic traits so

1713
01:08:44,149 --> 01:08:41,679
this can be a wonderful mechanism

1714
01:08:46,550 --> 01:08:44,159
facilitating evolution because anything

1715
01:08:49,349 --> 01:08:46,560
after a stop codon is not experiencing

1716
01:08:51,910 --> 01:08:49,359
selection pressure and can mutate freely

1717
01:08:57,349 --> 01:08:51,920
but after the prion is formed it

1718
01:09:00,870 --> 01:08:59,030
as i mentioned i'm very interested in

1719
01:09:03,349 --> 01:09:00,880
finding out what are the oldest pregnant

1720
01:09:04,550 --> 01:09:03,359
functions so recently machine learning

1721
01:09:05,990 --> 01:09:04,560
tools

1722
01:09:07,590 --> 01:09:06,000
were developed that allowed the

1723
01:09:10,709 --> 01:09:07,600
prediction

1724
01:09:12,870 --> 01:09:10,719
of prion behavior bioinformatically

1725
01:09:14,789 --> 01:09:12,880
based on amino acid sequences

1726
01:09:17,269 --> 01:09:14,799
so our recent work focused on

1727
01:09:19,829 --> 01:09:17,279
computational on computation on

1728
01:09:21,510 --> 01:09:19,839
bioinformatics and the future work will

1729
01:09:24,550 --> 01:09:21,520
again be

1730
01:09:26,709 --> 01:09:24,560
lab based prion confirmation of the

1731
01:09:28,630 --> 01:09:26,719
behavior of the protease

1732
01:09:30,630 --> 01:09:28,640
uh so the problem with prions is that

1733
01:09:32,630 --> 01:09:30,640
unfortunately their sequence of the

1734
01:09:35,110 --> 01:09:32,640
prion domain the fragment of the protein

1735
01:09:37,829 --> 01:09:35,120
that is responsible for aggregation

1736
01:09:40,470 --> 01:09:37,839
those prion domains are very homogeneous

1737
01:09:43,349 --> 01:09:40,480
and in many cases consist of just long

1738
01:09:46,149 --> 01:09:43,359
stretches of glutamine asparagine

1739
01:09:48,709 --> 01:09:46,159
this composition of preon domains

1740
01:09:51,110 --> 01:09:48,719
challenges the con the conventional

1741
01:09:52,070 --> 01:09:51,120
phylogenetic approach it's really hard

1742
01:09:55,030 --> 01:09:52,080
to say

1743
01:09:57,430 --> 01:09:55,040
if they are conserved based on sequence

1744
01:09:59,990 --> 01:09:57,440
uh pre and domains are modular that's

1745
01:10:01,110 --> 01:10:00,000
another characteristic of pre of prion

1746
01:10:02,790 --> 01:10:01,120
domains

1747
01:10:05,430 --> 01:10:02,800
that means that you can attach it to

1748
01:10:07,910 --> 01:10:05,440
another non-prion protein and convey the

1749
01:10:08,790 --> 01:10:07,920
ability to form a heritable aggregate to

1750
01:10:13,750 --> 01:10:08,800
it

1751
01:10:16,630 --> 01:10:13,760
identify candidate prion domains in all

1752
01:10:19,030 --> 01:10:16,640
proteomes of unipro from uniprot

1753
01:10:20,870 --> 01:10:19,040
uh proteums of organisms representing

1754
01:10:23,590 --> 01:10:20,880
all three domains of life

1755
01:10:25,270 --> 01:10:23,600
and then we annotate functional domains

1756
01:10:27,510 --> 01:10:25,280
of the candidate

1757
01:10:29,030 --> 01:10:27,520
uh using gene ontology and keg

1758
01:10:31,430 --> 01:10:29,040
description so the

1759
01:10:33,750 --> 01:10:31,440
the other domain except the prion domain

1760
01:10:36,950 --> 01:10:33,760
that exists in this polypeptide

1761
01:10:39,590 --> 01:10:36,960
uh so we analyze the functional domain

1762
01:10:42,950 --> 01:10:39,600
that coexists with prion domain and the

1763
01:10:45,110 --> 01:10:42,960
in the same polypeptide chain

1764
01:10:48,550 --> 01:10:45,120
uh so first we generated phallogenetic

1765
01:10:49,750 --> 01:10:48,560
trees marking the predicted preons in

1766
01:10:52,709 --> 01:10:49,760
all

1767
01:10:55,350 --> 01:10:52,719
uh available high quality proteomes the

1768
01:10:57,830 --> 01:10:55,360
blue lines on the tree indicate proteome

1769
01:10:59,990 --> 01:10:57,840
with uh at least one per pre on

1770
01:11:01,990 --> 01:11:00,000
candidate in it the bars around the

1771
01:11:04,630 --> 01:11:02,000
three indicate how many prion candidates

1772
01:11:06,390 --> 01:11:04,640
per proteom we have found so blue is

1773
01:11:09,270 --> 01:11:06,400
more than five green is more than ten

1774
01:11:10,070 --> 01:11:09,280
and fif and red is more than fifteen

1775
01:11:12,950 --> 01:11:10,080
uh

1776
01:11:14,790 --> 01:11:12,960
pre and candidates per thousand proteins

1777
01:11:16,630 --> 01:11:14,800
the take-home message is that eukarya

1778
01:11:18,709 --> 01:11:16,640
have much more prion candidates per

1779
01:11:21,350 --> 01:11:18,719
protein than other domains and it could

1780
01:11:23,910 --> 01:11:21,360
be that better protein aggregation

1781
01:11:26,390 --> 01:11:23,920
handling systems in eukaryotes allow

1782
01:11:29,910 --> 01:11:26,400
them to use prunes for more widely

1783
01:11:31,669 --> 01:11:29,920
avoiding lethal aggregations but

1784
01:11:33,350 --> 01:11:31,679
it could also just be a bias of a

1785
01:11:35,910 --> 01:11:33,360
prediction system that is trained on

1786
01:11:37,990 --> 01:11:35,920
eukaryotic proteins

1787
01:11:40,149 --> 01:11:38,000
so next we looked at enriched functions

1788
01:11:42,390 --> 01:11:40,159
of preon candidates in different domains

1789
01:11:44,470 --> 01:11:42,400
enriched means that these specific geo

1790
01:11:47,030 --> 01:11:44,480
terms were more likely to be found in

1791
01:11:53,510 --> 01:11:47,040
prion

1792
01:11:55,750 --> 01:11:53,520
domain and we found two enriched

1793
01:11:57,750 --> 01:11:55,760
functions coexisting with prion domains

1794
01:12:00,070 --> 01:11:57,760
that are conserved across all three

1795
01:12:03,669 --> 01:12:00,080
domains of life calcium ion binding and

1796
01:12:06,550 --> 01:12:03,679
helicases calcium ion biting is a common

1797
01:12:08,630 --> 01:12:06,560
for proteins engage in signaling and

1798
01:12:10,790 --> 01:12:08,640
this observation goes well

1799
01:12:13,510 --> 01:12:10,800
uh in line with the hypothesis that

1800
01:12:15,830 --> 01:12:13,520
prions can work as hubs that integrate

1801
01:12:18,070 --> 01:12:15,840
diverse inputs and actuate diverse

1802
01:12:20,310 --> 01:12:18,080
outputs as molecular switches

1803
01:12:22,709 --> 01:12:20,320
just like in signaling should do and

1804
01:12:25,590 --> 01:12:22,719
helicases can influence activity of many

1805
01:12:27,910 --> 01:12:25,600
genes at the same time and this can

1806
01:12:30,630 --> 01:12:27,920
provide immediate access to genetically

1807
01:12:33,669 --> 01:12:30,640
complex traits uh this role of prions

1808
01:12:35,830 --> 01:12:33,679
was already suggested in east and our

1809
01:12:38,390 --> 01:12:35,840
data shows that it could actually be a

1810
01:12:40,950 --> 01:12:38,400
concert function of prions and all

1811
01:12:43,830 --> 01:12:40,960
domains of life and potentially the most

1812
01:12:45,990 --> 01:12:43,840
ancient prion functions as well

1813
01:12:48,310 --> 01:12:46,000
so looking at keg annotations of

1814
01:12:50,470 --> 01:12:48,320
proteins annotated with geo as calcium

1815
01:12:52,470 --> 01:12:50,480
ion binding because consistently we

1816
01:12:55,030 --> 01:12:52,480
found the same description

1817
01:12:57,510 --> 01:12:55,040
uh in all domains of life but none of

1818
01:12:59,189 --> 01:12:57,520
them was yet shown to behave as a prion

1819
01:13:00,790 --> 01:12:59,199
an experiment so these are all very

1820
01:13:03,350 --> 01:13:00,800
interesting candidates to study in the

1821
01:13:06,070 --> 01:13:03,360
lab looking at keg annotations of

1822
01:13:08,709 --> 01:13:06,080
another they did as helicases we found

1823
01:13:11,030 --> 01:13:08,719
several confirmed prions in bacteria the

1824
01:13:13,350 --> 01:13:11,040
most common ko annotation was

1825
01:13:15,189 --> 01:13:13,360
transcription termination factor rho and

1826
01:13:17,669 --> 01:13:15,199
the rho protein was the first pre and

1827
01:13:20,630 --> 01:13:17,679
confirmed in bacteria specifically uh

1828
01:13:23,430 --> 01:13:20,640
clostridium botulinum so in eukaryotes

1829
01:13:26,709 --> 01:13:23,440
multiple different helicases showed up

1830
01:13:28,709 --> 01:13:26,719
in the data set including ddx 3 5 and 6.

1831
01:13:30,630 --> 01:13:28,719
in a very recent publication our

1832
01:13:32,229 --> 01:13:30,640
collaborators from stanford they showed

1833
01:13:35,030 --> 01:13:32,239
the ddx-5

1834
01:13:37,030 --> 01:13:35,040
uh forms cytoplasmic aggregates in old

1835
01:13:38,630 --> 01:13:37,040
fish and mice

1836
01:13:40,950 --> 01:13:38,640
and all they when they express it in

1837
01:13:43,270 --> 01:13:40,960
yeast that form heritable aggregates so

1838
01:13:46,070 --> 01:13:43,280
these experiments strength strengthens

1839
01:13:47,910 --> 01:13:46,080
our confidence in the prediction model

1840
01:13:49,270 --> 01:13:47,920
uh so let's go beyond the enriched

1841
01:13:51,590 --> 01:13:49,280
functions now

1842
01:13:54,550 --> 01:13:51,600
on the and we have to finish

1843
01:13:56,630 --> 01:13:54,560
all right so that's a conclusion

1844
01:13:59,030 --> 01:13:56,640
on the left side there is there are

1845
01:14:00,870 --> 01:13:59,040
numbers of overlapping

1846
01:14:02,709 --> 01:14:00,880
functions so there is many more if we're

1847
01:14:05,350 --> 01:14:02,719
not looking at the

1848
01:14:07,430 --> 01:14:05,360
enriched ones so i'd like to finish the

1849
01:14:10,229 --> 01:14:07,440
presentation with the hypothesis that we

1850
01:14:12,630 --> 01:14:10,239
came up uh during uh looking analyzing

1851
01:14:15,189 --> 01:14:12,640
this data that prion regulation

1852
01:14:17,510 --> 01:14:15,199
of the fundamental sub-processes could

1853
01:14:19,270 --> 01:14:17,520
be an evolutionary ancient one even if

1854
01:14:20,229 --> 01:14:19,280
the sequence of the individual pre and

1855
01:14:22,709 --> 01:14:20,239
domain

1856
01:14:24,709 --> 01:14:22,719
are not evolutionary conserved and thank

1857
01:14:26,390 --> 01:14:24,719
you so much for your attention and to my

1858
01:14:31,590 --> 01:14:26,400
co-workers

1859
01:14:34,709 --> 01:14:33,030
so

1860
01:14:36,550 --> 01:14:34,719
unfortunately we don't have time for

1861
01:14:39,270 --> 01:14:36,560
questions um

1862
01:14:40,950 --> 01:14:39,280
uh but uh moving along to our final uh

1863
01:14:42,870 --> 01:14:40,960
speaker of the session

1864
01:14:45,430 --> 01:14:42,880
uh foreign

1865
01:14:47,110 --> 01:14:45,440
will be uh

1866
01:14:49,189 --> 01:14:47,120
uh presenting work entitled the

1867
01:14:50,790 --> 01:14:49,199
phenotype of the last common

1868
01:14:55,110 --> 01:14:50,800
of the last universal common ancestor

1869
01:14:55,120 --> 01:14:59,750
and then three minutes

1870
01:15:18,550 --> 01:15:01,910
okay should they just close this and

1871
01:15:25,110 --> 01:15:21,669
uh hello everyone um

1872
01:15:27,990 --> 01:15:25,120
great to be here um most of the main

1873
01:15:31,189 --> 01:15:28,000
message let's say from today can be

1874
01:15:33,189 --> 01:15:31,199
summarized in the first conclusion of

1875
01:15:36,470 --> 01:15:33,199
antonio lascano talk

1876
01:15:39,590 --> 01:15:36,480
that is uh luca is probably a complex

1877
01:15:41,750 --> 01:15:39,600
population of cells that resembles

1878
01:15:44,070 --> 01:15:41,760
modern prokaryotes

1879
01:15:46,229 --> 01:15:44,080
uh i'm currently a research associate

1880
01:15:48,390 --> 01:15:46,239
working on malaria at harvard university

1881
01:15:50,310 --> 01:15:48,400
and broad institute but

1882
01:15:52,470 --> 01:15:50,320
let's talk about luca

1883
01:15:55,350 --> 01:15:52,480
so though

1884
01:15:57,510 --> 01:15:55,360
as laskano also has mentioned it uh luca

1885
01:15:58,310 --> 01:15:57,520
is is is way

1886
01:16:04,070 --> 01:15:58,320
uh

1887
01:16:08,470 --> 01:16:04,080
after life originated that is to say if

1888
01:16:11,270 --> 01:16:08,480
we consider the darwinian threshold

1889
01:16:15,030 --> 01:16:11,280
hypothesis suggested by ways that is

1890
01:16:18,630 --> 01:16:15,040
there is an rna world there is then

1891
01:16:20,550 --> 01:16:18,640
progeny note like up to lucas so when

1892
01:16:23,110 --> 01:16:20,560
talking about luca we are talking about

1893
01:16:24,630 --> 01:16:23,120
this common ancestor of our living

1894
01:16:27,350 --> 01:16:24,640
organism today

1895
01:16:31,030 --> 01:16:27,360
anything related to luca uh

1896
01:16:32,310 --> 01:16:31,040
reconstruction is subject to debate uh

1897
01:16:35,189 --> 01:16:32,320
obviously

1898
01:16:37,669 --> 01:16:35,199
so we all know this uh image and we grow

1899
01:16:39,750 --> 01:16:37,679
up with this with having a three domain

1900
01:16:43,110 --> 01:16:39,760
of life trees with bacteria arcane

1901
01:16:44,229 --> 01:16:43,120
eukarya and as you know the discovery of

1902
01:16:46,310 --> 01:16:44,239
asgard

1903
01:16:47,750 --> 01:16:46,320
archaea

1904
01:16:49,350 --> 01:16:47,760
and other

1905
01:16:51,590 --> 01:16:49,360
arcane

1906
01:16:53,030 --> 01:16:51,600
cells that share many characteristics

1907
01:16:53,830 --> 01:16:53,040
with eukaryotes

1908
01:16:56,070 --> 01:16:53,840
uh

1909
01:16:58,070 --> 01:16:56,080
lead us to think that there is probably

1910
01:17:00,390 --> 01:16:58,080
just two domains of life bacteria and

1911
01:17:03,430 --> 01:17:00,400
archaea with eukaryotes uh

1912
01:17:07,430 --> 01:17:03,440
is a group that emerged much later

1913
01:17:09,510 --> 01:17:07,440
uh during evolution with luca and its

1914
01:17:12,310 --> 01:17:09,520
derived um

1915
01:17:14,630 --> 01:17:12,320
and its distance like the last bacterial

1916
01:17:17,430 --> 01:17:14,640
common ancestor and the last rkl common

1917
01:17:20,390 --> 01:17:17,440
ancestor for which also

1918
01:17:22,630 --> 01:17:20,400
i will show some more constructions

1919
01:17:24,950 --> 01:17:22,640
so obviously when we come to the

1920
01:17:27,990 --> 01:17:24,960
reconstruction of ancestral states and

1921
01:17:30,390 --> 01:17:28,000
go back in time we usually use fossils

1922
01:17:33,990 --> 01:17:30,400
and fortunately for microbes

1923
01:17:35,189 --> 01:17:34,000
this is not possible and we therefore

1924
01:17:38,470 --> 01:17:35,199
rely on

1925
01:17:39,590 --> 01:17:38,480
mainly on the gene genomes or genetic

1926
01:17:42,830 --> 01:17:39,600
sequences

1927
01:17:46,310 --> 01:17:42,840
or uh other any other statistical

1928
01:17:48,149 --> 01:17:46,320
inference in order to reconstruct past

1929
01:17:49,189 --> 01:17:48,159
characters

1930
01:17:50,229 --> 01:17:49,199
so

1931
01:17:52,709 --> 01:17:50,239
uh

1932
01:17:56,310 --> 01:17:52,719
we for a long time luca has been taught

1933
01:17:58,229 --> 01:17:56,320
as a minimal or primitive cell like

1934
01:18:01,669 --> 01:17:58,239
maybe half a life and recent

1935
01:18:03,750 --> 01:18:01,679
reconstructions by ways it all have uh

1936
01:18:05,350 --> 01:18:03,760
concluded that luca must have been like

1937
01:18:06,990 --> 01:18:05,360
a very simple

1938
01:18:10,390 --> 01:18:07,000
cell with about

1939
01:18:13,510 --> 01:18:10,400
350 proteins this is the just to give

1940
01:18:16,630 --> 01:18:13,520
you an idea is about the size of on the

1941
01:18:19,669 --> 01:18:16,640
obligates on the symbiotic bacteria that

1942
01:18:21,030 --> 01:18:19,679
we found we find today so all of the

1943
01:18:23,510 --> 01:18:21,040
reconstructions

1944
01:18:25,830 --> 01:18:23,520
that we know of are based on the absence

1945
01:18:29,350 --> 01:18:25,840
or presence of genes

1946
01:18:30,149 --> 01:18:29,360
and based on genome genomic data here i

1947
01:18:30,950 --> 01:18:30,159
will

1948
01:18:33,830 --> 01:18:30,960
uh

1949
01:18:36,390 --> 01:18:33,840
talk about a different approach that is

1950
01:18:39,910 --> 01:18:36,400
based on on on on

1951
01:18:41,590 --> 01:18:39,920
a phenotype and not genomes so we know

1952
01:18:44,070 --> 01:18:41,600
that it is still

1953
01:18:47,350 --> 01:18:44,080
inherently difficult to predict

1954
01:18:49,030 --> 01:18:47,360
phenotype simply by a presence or

1955
01:18:51,750 --> 01:18:49,040
absence of genes although we can do it

1956
01:18:53,189 --> 01:18:51,760
in some cases and here we will use so if

1957
01:18:55,510 --> 01:18:53,199
we consider

1958
01:18:57,750 --> 01:18:55,520
observing traits that we have today

1959
01:18:59,350 --> 01:18:57,760
let's say mortality or shape or whatever

1960
01:19:01,430 --> 01:18:59,360
so you we can use

1961
01:19:04,229 --> 01:19:01,440
in this example by asian

1962
01:19:08,310 --> 01:19:04,239
inferences and using a

1963
01:19:10,870 --> 01:19:08,320
markov models and we can infer

1964
01:19:13,110 --> 01:19:10,880
ancestral states and obtain some

1965
01:19:15,590 --> 01:19:13,120
posterior probabilities

1966
01:19:17,189 --> 01:19:15,600
for for those states

1967
01:19:19,350 --> 01:19:17,199
so

1968
01:19:22,790 --> 01:19:19,360
those ancestral state reconstruction

1969
01:19:26,310 --> 01:19:22,800
methods has been used to for like

1970
01:19:28,630 --> 01:19:26,320
diatoms that has been done also on other

1971
01:19:31,669 --> 01:19:28,640
eukaryotes and more recently we we used

1972
01:19:34,830 --> 01:19:31,679
this method to reconstruct uh ancestral

1973
01:19:36,870 --> 01:19:34,840
states for fermicutes uh bacteria

1974
01:19:39,030 --> 01:19:36,880
so to

1975
01:19:41,270 --> 01:19:39,040
reconstruct the character the ancient

1976
01:19:44,630 --> 01:19:41,280
character of lucca i have collected more

1977
01:19:47,030 --> 01:19:44,640
than 3 000 phenotypic characters and i

1978
01:19:47,750 --> 01:19:47,040
went during three years and a half over

1979
01:19:50,550 --> 01:19:47,760
the

1980
01:19:53,510 --> 01:19:50,560
berges manual of systematic bacteriology

1981
01:19:54,310 --> 01:19:53,520
and we collected data on shape motility

1982
01:19:57,110 --> 01:19:54,320
uh

1983
01:19:58,790 --> 01:19:57,120
environmental data spar formation

1984
01:19:59,990 --> 01:19:58,800
membrane etc

1985
01:20:02,709 --> 01:20:00,000
and

1986
01:20:06,310 --> 01:20:02,719
obviously when we reconstruct ancestral

1987
01:20:08,709 --> 01:20:06,320
states uh there is the problem of uh or

1988
01:20:11,510 --> 01:20:08,719
horizontal gene transfer in our case

1989
01:20:15,110 --> 01:20:11,520
what we did is we did some simulations

1990
01:20:16,950 --> 01:20:15,120
on a horizontal trade transfer that is

1991
01:20:19,110 --> 01:20:16,960
considering a trait

1992
01:20:20,229 --> 01:20:19,120
uh and how it can be transferred and how

1993
01:20:23,030 --> 01:20:20,239
this

1994
01:20:25,270 --> 01:20:23,040
transfer might impact our constructions

1995
01:20:28,149 --> 01:20:25,280
and just to summarize here what i want

1996
01:20:30,310 --> 01:20:28,159
to see to show you we did two

1997
01:20:32,310 --> 01:20:30,320
different simulations one that is a

1998
01:20:35,750 --> 01:20:32,320
local transfer approach and the second

1999
01:20:38,470 --> 01:20:35,760
one is a global transfer approach and

2000
01:20:41,350 --> 01:20:38,480
we expect that using a bromanian motion

2001
01:20:44,390 --> 01:20:41,360
model and we and we expect that the the

2002
01:20:46,310 --> 01:20:44,400
slot will in any case and

2003
01:20:47,669 --> 01:20:46,320
that it doesn't impact our construction

2004
01:20:50,550 --> 01:20:47,679
it will be one

2005
01:20:53,430 --> 01:20:50,560
and as you can see the more we increase

2006
01:20:56,950 --> 01:20:53,440
the number of simulation up to 1000

2007
01:20:58,950 --> 01:20:56,960
for the local uh inference for local

2008
01:21:01,030 --> 01:20:58,960
transfer it does not impact

2009
01:21:03,830 --> 01:21:01,040
significantly our inference but for the

2010
01:21:07,030 --> 01:21:03,840
global transfer when we simulate this up

2011
01:21:10,229 --> 01:21:07,040
to 1000 event there is a huge

2012
01:21:12,629 --> 01:21:10,239
variance and obviously it does impact

2013
01:21:16,390 --> 01:21:12,639
the the the inferences

2014
01:21:19,510 --> 01:21:16,400
so what's we have reconstructed so based

2015
01:21:21,910 --> 01:21:19,520
on uh this method uh and the biasing

2016
01:21:24,790 --> 01:21:21,920
framework we reconstructed luca as a

2017
01:21:27,590 --> 01:21:24,800
halo tolerant hyperthermophile or

2018
01:21:30,470 --> 01:21:27,600
although it is still there is debate

2019
01:21:32,950 --> 01:21:30,480
about the hyperthermophilia fluca it was

2020
01:21:34,790 --> 01:21:32,960
uh it has evolved in neutral ph and in

2021
01:21:38,070 --> 01:21:34,800
aquatic environments

2022
01:21:40,709 --> 01:21:38,080
uh it was anaerobic uh chemologotrophic

2023
01:21:43,830 --> 01:21:40,719
and uh curiously it has catalase and

2024
01:21:46,149 --> 01:21:43,840
oxidase which exists that it might uh

2025
01:21:48,149 --> 01:21:46,159
it was probably able to resist oxidative

2026
01:21:50,870 --> 01:21:48,159
stress uh

2027
01:21:53,110 --> 01:21:50,880
but we know that concentration of oxygen

2028
01:21:54,830 --> 01:21:53,120
at that time might have been like

2029
01:21:57,750 --> 01:21:54,840
less than

2030
01:21:59,590 --> 01:21:57,760
0.001 uh so

2031
01:22:01,910 --> 01:21:59,600
this the presence of catalyst and

2032
01:22:03,990 --> 01:22:01,920
oxidase may be also due to the fact of

2033
01:22:05,350 --> 01:22:04,000
possible horizontal ancient horizontal

2034
01:22:08,950 --> 01:22:05,360
gene transfer

2035
01:22:11,189 --> 01:22:08,960
so the the the distance of

2036
01:22:13,430 --> 01:22:11,199
other distance of luca the last rkl

2037
01:22:15,990 --> 01:22:13,440
common ancestor has also similar

2038
01:22:17,750 --> 01:22:16,000
characteristics as luca has been halo

2039
01:22:20,390 --> 01:22:17,760
turreted hollow tolerant

2040
01:22:23,270 --> 01:22:20,400
hyperthermophile we were not sure if it

2041
01:22:25,430 --> 01:22:23,280
was aerobic or anaerobic

2042
01:22:27,750 --> 01:22:25,440
for the last bacterial common ancestor

2043
01:22:30,470 --> 01:22:27,760
it was also anaerobic hemolytotrophic it

2044
01:22:33,350 --> 01:22:30,480
has also catalyzed and

2045
01:22:35,669 --> 01:22:33,360
it was halo tolerance and thermophile it

2046
01:22:37,669 --> 01:22:35,679
was not hyperthermophile but thermophile

2047
01:22:38,550 --> 01:22:37,679
and evolving neutral ph

2048
01:22:39,669 --> 01:22:38,560
so

2049
01:22:41,750 --> 01:22:39,679
for now

2050
01:22:44,629 --> 01:22:41,760
anything that we think about luca like

2051
01:22:46,790 --> 01:22:44,639
for example it's a morphology it's based

2052
01:22:49,990 --> 01:22:46,800
on intuition so we think that it might

2053
01:22:51,830 --> 01:22:50,000
have looked like a prokaryote but it's

2054
01:22:54,709 --> 01:22:51,840
we never when

2055
01:22:56,229 --> 01:22:54,719
it has never been reconstructed so

2056
01:22:58,470 --> 01:22:56,239
here we

2057
01:23:01,590 --> 01:22:58,480
the variety of bacterial shape or

2058
01:23:03,590 --> 01:23:01,600
archaeal shape is huge but we we summer

2059
01:23:05,510 --> 01:23:03,600
we simplify this into three main

2060
01:23:07,990 --> 01:23:05,520
categories like cocoid that is just

2061
01:23:10,629 --> 01:23:08,000
divide and the road that it has a known

2062
01:23:13,270 --> 01:23:10,639
elongation machinery and avoid

2063
01:23:14,390 --> 01:23:13,280
that has like a septal growth and then

2064
01:23:17,030 --> 01:23:14,400
division

2065
01:23:19,189 --> 01:23:17,040
so when we and feared uh reconstructed

2066
01:23:23,110 --> 01:23:19,199
the ancestral state we found that luca

2067
01:23:25,350 --> 01:23:23,120
was probably an avoid motile cell that

2068
01:23:27,350 --> 01:23:25,360
has a monodermic uh

2069
01:23:29,910 --> 01:23:27,360
it was monoderm like having a

2070
01:23:32,709 --> 01:23:29,920
once a single membrane and we were not

2071
01:23:36,149 --> 01:23:32,719
sure it was performing or not and it has

2072
01:23:37,669 --> 01:23:36,159
a genome size of approximately 2.5 which

2073
01:23:39,430 --> 01:23:37,679
is close to

2074
01:23:41,189 --> 01:23:39,440
current

2075
01:23:44,070 --> 01:23:41,199
genome size in some

2076
01:23:46,790 --> 01:23:44,080
bacteria and archaea so the rkl common

2077
01:23:49,590 --> 01:23:46,800
ancestor was also avoid motile has a

2078
01:23:52,149 --> 01:23:49,600
cell wall and was monodermic

2079
01:23:55,590 --> 01:23:52,159
and the last bacterial common ancestor

2080
01:23:57,910 --> 01:23:55,600
was likely a rod shaped uh

2081
01:24:00,229 --> 01:23:57,920
like bacterium it has a cell wall we

2082
01:24:02,390 --> 01:24:00,239
were not sure it was monodermic and it

2083
01:24:04,709 --> 01:24:02,400
had it was probably spore

2084
01:24:07,750 --> 01:24:04,719
non-sport-forming this reconstruction of

2085
01:24:10,709 --> 01:24:07,760
the last bacterial common ancestor is uh

2086
01:24:12,790 --> 01:24:10,719
similar to what has just been done

2087
01:24:15,189 --> 01:24:12,800
recently by coleman using a genomic

2088
01:24:16,550 --> 01:24:15,199
approach except that they found it was a

2089
01:24:18,870 --> 01:24:16,560
dynamic

2090
01:24:19,910 --> 01:24:18,880
cell

2091
01:24:22,149 --> 01:24:19,920
so

2092
01:24:26,550 --> 01:24:22,159
given this complexity of

2093
01:24:29,189 --> 01:24:26,560
luca shape and size and genome it's

2094
01:24:32,550 --> 01:24:29,199
given the also the the earth formation

2095
01:24:35,270 --> 01:24:32,560
timeline and given uh when

2096
01:24:37,910 --> 01:24:35,280
the luca had appeared on earth at the

2097
01:24:42,390 --> 01:24:37,920
first time life must have been evolved

2098
01:24:45,110 --> 01:24:42,400
very quickly uh cellular into complex

2099
01:24:49,030 --> 01:24:45,120
cells and it was probably as much

2100
01:24:51,270 --> 01:24:49,040
complex as many uh modern uh

2101
01:24:52,070 --> 01:24:51,280
bacteria and archaea

2102
01:24:53,590 --> 01:24:52,080
so

2103
01:24:55,750 --> 01:24:53,600
this is one of the

2104
01:24:58,470 --> 01:24:55,760
message the second message i want to

2105
01:25:00,709 --> 01:24:58,480
tell you and that is for me very

2106
01:25:01,910 --> 01:25:00,719
important since i've i've

2107
01:25:04,870 --> 01:25:01,920
worked with

2108
01:25:07,990 --> 01:25:04,880
many biophysicists and mathematicians is

2109
01:25:12,390 --> 01:25:08,000
the scale at which we are uh observing

2110
01:25:14,870 --> 01:25:12,400
or studying uh luca or microbes so

2111
01:25:16,350 --> 01:25:14,880
at the small scale at the micro scale

2112
01:25:18,790 --> 01:25:16,360
the physics became

2113
01:25:21,510 --> 01:25:18,800
counterintuitive it's not the physics we

2114
01:25:23,189 --> 01:25:21,520
are experiencing daily gravity has not

2115
01:25:25,990 --> 01:25:23,199
the same importance that it has on

2116
01:25:28,470 --> 01:25:26,000
macroscopic organisms and by studying

2117
01:25:31,430 --> 01:25:28,480
microbes and by reconstructing ancestral

2118
01:25:33,189 --> 01:25:31,440
environment or ancestral uh selective

2119
01:25:34,950 --> 01:25:33,199
pressure uh

2120
01:25:38,310 --> 01:25:34,960
even at the time of luca we have to

2121
01:25:40,709 --> 01:25:38,320
consider the micro scale biophysics like

2122
01:25:43,270 --> 01:25:40,719
for example the low reynold numbers in

2123
01:25:45,430 --> 01:25:43,280
which it evolves brownian motion

2124
01:25:49,270 --> 01:25:45,440
kinematic reversibility and molecular

2125
01:25:52,149 --> 01:25:49,280
diffusion just to cite a few

2126
01:25:54,950 --> 01:25:52,159
so this is very important elements in

2127
01:25:56,629 --> 01:25:54,960
when studying microbes we tend generally

2128
01:25:59,189 --> 01:25:56,639
i i highlight this because we tend

2129
01:26:01,430 --> 01:25:59,199
generally as microbiologists to think

2130
01:26:03,990 --> 01:26:01,440
with our intuitive

2131
01:26:05,590 --> 01:26:04,000
physics uh when observing microbes while

2132
01:26:07,830 --> 01:26:05,600
we should not

2133
01:26:09,510 --> 01:26:07,840
finally if we look at

2134
01:26:10,470 --> 01:26:09,520
life in in space

2135
01:26:16,550 --> 01:26:10,480
i will

2136
01:26:20,790 --> 01:26:16,560
probably it will be microbial first

2137
01:26:23,270 --> 01:26:20,800
before it can be in if if we find

2138
01:26:26,229 --> 01:26:23,280
life in at least our solar system i will

2139
01:26:28,550 --> 01:26:26,239
look for microbials and i will look for

2140
01:26:32,950 --> 01:26:28,560
motility i will look for dna i will look

2141
01:26:36,229 --> 01:26:32,960
for any sign that is uh that is that is

2142
01:26:38,790 --> 01:26:36,239
uh that is similar to what we observe on

2143
01:26:41,110 --> 01:26:38,800
on microbes on earth

2144
01:26:43,350 --> 01:26:41,120
and with this i would like to thank my

2145
01:26:46,709 --> 01:26:43,360
colleagues and collaborators stewards

2146
01:26:55,990 --> 01:26:46,719
say chris and andrew and thanks if you

2147
01:27:03,990 --> 01:26:57,669
great thank you so we have time for a

2148
01:27:07,990 --> 01:27:05,510
on the left

2149
01:27:11,669 --> 01:27:08,000
thank you very much for watching again

2150
01:27:15,910 --> 01:27:13,189
and you mentioned that there is no

2151
01:27:16,830 --> 01:27:15,920
participation of gravity due to small

2152
01:27:20,070 --> 01:27:16,840
size

2153
01:27:23,189 --> 01:27:20,080
right i said it's negligible it's very

2154
01:27:27,270 --> 01:27:23,199
negligible in comparison to to our scale

2155
01:27:29,270 --> 01:27:27,280
yeah so on a scale of a sphere of a one

2156
01:27:32,790 --> 01:27:29,280
micron

2157
01:27:34,950 --> 01:27:32,800
considering different uh in a

2158
01:27:37,830 --> 01:27:34,960
in a density 10 percent

2159
01:27:41,110 --> 01:27:37,840
is going to descend in a water with a

2160
01:27:44,149 --> 01:27:41,120
speed uh one millimeter per hour

2161
01:27:47,350 --> 01:27:44,159
if it's a five micron it's a

2162
01:27:51,270 --> 01:27:47,360
one millimeter uh no sorry

2163
01:27:52,950 --> 01:27:51,280
one micron is about 24 hours and five

2164
01:27:55,590 --> 01:27:52,960
microns uh

2165
01:27:57,350 --> 01:27:55,600
radius is about uh

2166
01:27:59,270 --> 01:27:57,360
one hour

2167
01:28:01,830 --> 01:27:59,280
yes approximately

2168
01:28:02,950 --> 01:28:01,840
so it's a it's still

2169
01:28:04,470 --> 01:28:02,960
sizeable

2170
01:28:06,790 --> 01:28:04,480
moving

2171
01:28:09,990 --> 01:28:06,800
it does what i mean by that it's it's it

2172
01:28:12,310 --> 01:28:10,000
will not have really the same impact as

2173
01:28:13,830 --> 01:28:12,320
it at of course it has

2174
01:28:16,709 --> 01:28:13,840
there is there is gravity that's

2175
01:28:17,590 --> 01:28:16,719
mosquito gravity at all scales but it is

2176
01:28:20,149 --> 01:28:17,600
not

2177
01:28:22,390 --> 01:28:20,159
in term of evolutionary impact or

2178
01:28:25,270 --> 01:28:22,400
selective pressures i don't think it

2179
01:28:28,229 --> 01:28:25,280
will be comparable to what we observe uh

2180
01:28:29,910 --> 01:28:28,239
on on macro scale organisms that's just

2181
01:28:33,030 --> 01:28:29,920
what i mean yeah unless selective

2182
01:28:35,750 --> 01:28:33,040
pressure is uv

2183
01:28:37,830 --> 01:28:35,760
yeah so thank you next question

2184
01:28:38,790 --> 01:28:37,840
all right that was a great thought thank

2185
01:28:40,629 --> 01:28:38,800
you thank you

2186
01:28:43,350 --> 01:28:40,639
can you tell us about

2187
01:28:46,390 --> 01:28:43,360
what you think that happened between the

2188
01:28:48,070 --> 01:28:46,400
in terms of the the genomic genomic

2189
01:28:50,390 --> 01:28:48,080
increase between the last universal

2190
01:28:51,270 --> 01:28:50,400
common ancestor and to the last

2191
01:28:53,750 --> 01:28:51,280
uh

2192
01:28:55,590 --> 01:28:53,760
bacterial common ancestor because it

2193
01:28:57,430 --> 01:28:55,600
seems that you found like

2194
01:28:59,430 --> 01:28:57,440
some increase in the genome right but

2195
01:29:02,070 --> 01:28:59,440
not in the last uh

2196
01:29:05,590 --> 01:29:02,080
archaea common ancestor

2197
01:29:08,950 --> 01:29:05,600
you mean here yeah from

2198
01:29:11,750 --> 01:29:08,960
2.5 to do you think that was like a new

2199
01:29:12,950 --> 01:29:11,760
genome new genes evolving like or gene

2200
01:29:14,709 --> 01:29:12,960
transfer

2201
01:29:16,709 --> 01:29:14,719
or doubling of

2202
01:29:17,830 --> 01:29:16,719
like genomic duplication something like

2203
01:29:21,430 --> 01:29:17,840
this

2204
01:29:23,669 --> 01:29:21,440
that's a good question i i personally uh

2205
01:29:25,270 --> 01:29:23,679
i i i don't have like a clear

2206
01:29:26,310 --> 01:29:25,280
explanation for that

2207
01:29:28,229 --> 01:29:26,320
uh

2208
01:29:30,950 --> 01:29:28,239
all what i can say that there is the

2209
01:29:33,430 --> 01:29:30,960
constructions were done independently so

2210
01:29:35,830 --> 01:29:33,440
we didn't we we tested for trends if

2211
01:29:38,870 --> 01:29:35,840
there is increase or decrease uh in

2212
01:29:40,149 --> 01:29:38,880
genome through time uh using different

2213
01:29:41,750 --> 01:29:40,159
phylogenies

2214
01:29:45,270 --> 01:29:41,760
but we

2215
01:29:47,830 --> 01:29:45,280
we i didn't specifically test for like

2216
01:29:50,229 --> 01:29:47,840
the the increase or decrease for from

2217
01:29:52,470 --> 01:29:50,239
luca to laca for example

2218
01:29:54,629 --> 01:29:52,480
but thanks that's a good question yeah

2219
01:29:56,709 --> 01:29:54,639
so unfortunately we're out of time yes

2220
01:30:02,229 --> 01:29:56,719
sure uh but let's thank our speakers

2221
01:30:05,830 --> 01:30:04,070
and yeah and thank you everyone for your