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yeah my name is Kenny I know it's really

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difficult sorry and I guess I'm one of

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the people that you don't envy because

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I'm going to try to talk about amino

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acid biosynthetic pathways and so amino

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acids are critical and that they are the

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constituents of the proteins which carry

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out the functions in a cell and it's

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thought that the last Universal common

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ancestor or the root of the tree of life

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is able to prevail to produce all

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currently available amino acids so I'm

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interested in characterizing things at

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the last Universal common ancestor and

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obviously in the context of the

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progression of the central dogma or

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these other molecular processes so uh so

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the first question that I had with this

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project is whether the conservation of

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proteins associated with amino acid

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biosynthesis would be related to a

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characteristic of the amino acid like

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the complexity of them so I I have a by

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automatic approach where I compare

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features across species or the whole

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tree of life based on either the gene or

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protein level and extrapolate this

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information on to the last Universal

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common ancestor so a super cool a

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postdoc in the lab Aaron who seems to be

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here in spirit is he got a shout out

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earlier to curated this database called

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Luca pedia which basically is a

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combination of several different data

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sets that attempt to characterize

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ancient characteristics of proteins

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based on these universal type

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distributions and they use different

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approaches so there's different types of

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ways you can approach this obviously you

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can do it by gene families by

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universally distributed protein motifs

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some of these studies use different

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structural perspectives as in protein

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folds or groups of protein fold

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functions and common reactions across

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the domains of life so in terms of

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complexity one of the reference

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I'm using his proxy is the abundance of

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certain prebiotic synthesis experiments

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so here I just have a table of the

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genetic code where I have the codon on

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the left and the corresponding amino

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acid on the right and the shading just

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corresponds with higher abundance in

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these experiments so I use a pretty

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simple diaphragmatic pipeline I start

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with a set of amino acid related

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proteins and I match these with things

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that I found in at least three of the

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studies in the database and I couple

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that with some ID matching which i use

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the ends on commission code for these

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proteins which is just a annotation for

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classes of enzyme function where you

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have four digits in each digit confers

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more specificity and description of the

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function of the enzyme and I did this

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within without the last digit which

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usually describes some substrate

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specificity of the enzyme so then I've

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mapped these things onto whoa then I met

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these things onto specific pathways to

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see where things were conserved in pasay

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puces so here's a one really cool

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pathway and what you're looking at in

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red throughout the pathway of the enzyme

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the three digit enzyme Commission codes

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that are conserved or match three at

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least three of these papers and the data

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set in the database and it looks a

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little daunting at first but if I peel

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off things that are not conserved you

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can see that there are these functional

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cores that seem to be conserved

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throughout the pathway so while the main

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products in this pathway are sharing

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glycine and threonine you can still see

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some really close metabolic proximity as

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and steps of reactions to get to other

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amino acids there's tryptophan over here

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since a cytosine then methenamine over

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here and other amino acid biosynthetic

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pathways as well as metabolism so when I

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looked at the main products of this

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pathway in in terms of these abundance

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proxies there's no direct correlation

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between the conservation and the

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complexity or

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of the amino acid which was at first not

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what I expected so another path or that

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is probably really representative of the

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convergence and not entirely surprising

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is valine isoleucine and loosing pathway

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in which the pathways are identical

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until you get to this last step of this

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last reaction so that's probably the

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best example of convergent pathways and

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given these sets so throughout their

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data oh man so throughout the data

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there's a there were several nodal

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proteins or consistently represented

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enzymes in all of these pathways or most

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of these pathways and that was

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depends synthase alpha chain and searing

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methyl ease and right so like I said

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their presidents everly these super

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pathways and they both um convert

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different functions to prevent synthase

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obviously the last two sets of

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tryptophan biosynthesis and searing

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methylase catalyzing the searing the

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glycine reaction as well as hydrolysis

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of tetrahydrofolate which is just the

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common cofactor in amino acid metabolism

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as well as nucleotide metabolism so I

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tried to find of models of enzyme

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evolution that would possibly fit the

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data I have and the patchwork model

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seems to be a really popular model that

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may correspond where you start out with

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these initially broadly reactive enzymes

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like red green and blue pac-man shape

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thing and you they do sir favor a

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certain reaction but they're still

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broadly reactive and after gene

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duplication the least thing and

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selection from the environment things

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become more specific in their function

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so I thought maybe this could help

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explain or maybe I'm seeing an artifact

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of this with these multifunctional nodes

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also another popular theory is a semi

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enzymatic theory where you have

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reactions that become linked some way

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and also it incorporates the use of

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spontaneous reactions and development of

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these processes so I guess my main

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inclusions are that you are able to

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identify certain functional chords that

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are conserved throughout these pathways

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and possibly their support for current

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models of enzyme evolution with this

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data with these data and I have to

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acknowledge my pile or landlubber other

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members of the lab do which are in the

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audience but not in this picture and of

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course Aaron Goldman who is responsible

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for curating the database that I worked

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so closely with so thank have any

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questions for Kinner II oh okay well

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then I have one um I don't know a whole

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lot about where in the cells amino acid

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biosynthesis take place if it's all in

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one place or if it's spread out is there

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any locational tendencies I realize it

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might not be a fair question well I'm

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I'm not quite sure I don't and this is

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probably personal I don't think of it as

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a localized reset of reactions but not