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[Music]

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[Applause]

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so I've truncated my title down to wet

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dry environmental cycles and alternative

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building blocks in prebiotic chemistry

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and as Bruce said I'm going to talk

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about some of the successes we've had in

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the Center for chemical evolution I'm

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also going to start out with some of our

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guiding principles or if you will

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truisms and hypotheses that have been

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guiding our research you can decide

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whether you think something is true or

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it's a hypothesis or how quite

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questionable I'll say that we follow the

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principle life is based on polymers that

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the emergence of biopolymers was

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essential to the origins of life and

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that the synthesis that the first

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syntheses of biopolymers was a result of

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geophysical geochemical cycles and what

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I'd like to just say special organic

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molecules specialized in special

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properties not necessarily rare and I'll

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continue and say that the molecules and

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reactions that gave rise to the first

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power polymers were simple maybe special

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but simple and robust and I'll go on to

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say that this is a principle that's been

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guiding us for over a decade and we say

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that if an experiment the mall model for

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a particular step in the origin of life

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is correct then we think that the model

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should solve more problems than just the

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problem that the model is designed to

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solve in the very least it should not

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generate more but ideally if you're on

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the right track it should solve more

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problems than you know and if that's

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true then you should discover what we

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call bonus solutions so I'll start with

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inspiration on the design of our

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experiments and that's extant

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biopolymers then all of these are

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synthesized by what are called

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condensation bonds such as two amino

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acids linked together give off water and

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the formation of condensation bond you

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keep doing that

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you know acids each time a water comes

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off to make a polypeptide same thing

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with polysaccharides nucleic acids and

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lipids those type of bonds present what

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is the first problem that we had to

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address which is the best place to form

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condensation ponds is in a hot dry

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environment because if you want to drive

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this reaction to the right you want to

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get rid of water so a surface arid

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surface is the best place but

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biopolymers they followed they function

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and they evolved in water you know

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that's a principle of them so we look

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for simple solutions that's what we've

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been focused on a simple solution to

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this is that the polymers of life were

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originally formed on the surface of the

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earth as a result of wet/dry cycles this

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is not a new idea we think that it's

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though parsimoniously the most obvious

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solution to it fits really well with the

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chemistry of the polymers with possible

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environments on the earth however early

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on we ran into another problem with this

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which is that this idea again is not new

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and attempts to make polypeptides by

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simply drying and heating amino acids

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have not provided satisfactory results

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we know that some of the earliest

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attempts to make vial polymers were from

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Sidney Fox and his collaborators and

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back in the 50s they had a results are

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pretty high temperatures that resulted

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in non peptide products there's been

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some nice advances in that area again

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but we've got some issues still Lahav

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Road and others have looked to do this

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under lower temperatures where you don't

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get those side products they typically

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get pretty low yields about one to two

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percent of just dipeptides or

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tripeptides

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so a possible solution to this problem

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is that polypeptides are preceded by

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what we'll call proto polypeptides with

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structures chemical linkages that are

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similar but distinct okay and that's

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important just change one atom and it

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can totally change the chemical

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properties of a molecule so they were

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similar but distinct from polypeptides

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so an obvious one would be that

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polypeptides were preceded by polyesters

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again not in not a original

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my idea the ester linkage was proposed

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back at least 1971 by rich and and then

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later or Gail discussed it and we liked

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this idea a lot because amino acids have

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hydroxy acids as analogues just change

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the amino group to hydroxyl group there

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and hydroxy acids they're used in life

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today they're produced in milli your

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experiments are found in meteorites so

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it looked like a real possibility that

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life would have started with polyesters

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so that's a simple solution and what we

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did find is that if we dry down these

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hydroxy acids what we do make ester

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linked oligomers just shown here as a

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lactic acid dimer but this is the first

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bonus that we found in pursuing this is

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that hydroxy acids catalyze peptide bond

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formation and what we found is that if

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we mix them you know acids in with the

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products of hydroxy acid condensation or

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even just start at the beginning and mix

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them all together that we have a mean

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ester exchange that leads to peptide

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bond formation so that to us was was a

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big bonus and so we thought the idea of

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using hydroxy acid looks like a really

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good route to polypeptides now there

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were some other bonuses that came out

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what we found is that if you look in the

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literature there was quite a bias on

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just drawing down the amino acids on

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what the composition is what sequences

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were favored and what we found from the

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start just mixing glycine and alanine

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that we were able to get all the

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sequences that were possible this is our

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initial results where we're just doing

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alanine and glycine and just looking at

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these Penta Murs here we're just based

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upon the molecular weight they have two

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lactic acids in and through one alanine

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and one and two glycines that we see

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that we got all possible sequences we

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took this further where we did mixtures

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with more amino acids and more hydroxy

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acids and what we found is that the

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sequence space that we generated is

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enormous in fact we we had to develop

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new methods that's what's illustrated

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here by these 3d plots actually even in

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a four dimensional plot to show the

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diversity of products that that were

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generating so it's again a big bonus

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beyond what we had expected there and

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I'm going to add one very recent bonus

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that's gonna come out very soon which is

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that drying these mixtures where we look

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at the difference between the

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proteinaceous amino acids and non

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protease that is those that are found in

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the coding of proteins versus those that

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are not there seems to be a preference

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here for the incorporation at least in

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the cationic amino acids for the

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proteinaceous woods which may be telling

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us something about why and how early

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lysine and arginine were selected into

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polypeptides so this study here was

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headed up by Moran Pinter and Lou

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Clayman and Lauren Williams really

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acting as the main PI's on this project

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and as I said this is coming out very

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soon just accepted yesterday and if you

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want to hear it talk on this Moran is

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giving a talk tomorrow on this so

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there's a similar story when it comes to

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nucleic acids and I will hopefully admit

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nucleic acids are more complex than

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polypeptides we know you can make the

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building blocks of polypeptides amino

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acids and model prebiotic reactions

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there's a lot of challenges with sugars

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less with bases there's challenges

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phosphate but then these all have to be

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connected into nucleotides and they're

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polymerized so those are additional

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challenges so in the CC we've also been

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hypothesizing that RNA as a result of

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multiple evolutionary steps that the

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base sugar connecting molecules have all

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changed something that we wrote about in

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a paper we called my grandfather's axe a

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few years ago and again what are the

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problems that we have with nucleic acids

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well one of them is that in a simple

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model prebiotic reaction where the

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extant bases are dried with ribose they

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produce nucleosides in either low yield

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or in no yield so this has been a big

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problem

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in the field again a simple solution to

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this could be that the nucleobases that

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were in proto RNA an ancestor of RNA

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were different in this case we've looked

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at melamine I'm showing you here and

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barbecue rock acid you could see this is

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perhaps taking the place of adenine and

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this is taking the place of your cell we

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tested these molecules and simple dry

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down reactions melamine gives us 55

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percent yield of both the alpha and beta

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anomers of the nucleotides and Barbic

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tear gas that gives us 82 so these work

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really well we also get bonuses though

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these alternative nucleobases those that

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form glycosides very easily with rivals

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with ribose also form them with many

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different sugars basically every sugar

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that we tested except for some modified

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sugars are showing the formation of

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glycosides with our bases so this could

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relax the constraints on getting ribose

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first david fiallo and Tyler Roach are

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working on this so you can talk to them

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they're here at this meeting and Tyler

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is giving a talk tomorrow

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on this topic another bonus that we

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found is that these alternative

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nucleobases self-assemble in water as

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monomers the extant bases don't do that

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you could see here this is an AFM image

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of non-covalent assemblies yet another

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bonus that we found with this is that

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they have a very very strong propensity

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to adopt homo chiral domains

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dr. Shanice Caro and karna is here and

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he will be giving a poster tonight and a

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lightning talk on Friday about how these

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plausible prebiotic bases make these

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homo chiral domains which we are quite

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excited about yet another bonus is that

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if we take what we've learned from our

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polypeptide work and our nucleo base

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work our pro to nuclear base work we put

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them together and we can now see just

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what might be possible structures for

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proto RNA these are just theoretical but

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I think that these have a lot

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the attributes that we would look be

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looking for for a very simple system

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that could be composed out of plausible

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prebiotic building blocks they can

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polymerize and start to evolve and again

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David and Senesh are here and David will

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be giving a poster tonight and the

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Lightning talked about this system so

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these are not all of the collaborators

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in the CCE but I've tried to pick the

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ones that I've highlighted the work on

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you can see this is a huge team effort

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and I feel very fortunate to work with

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so many talented people and there's even

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more here's the at the last Center

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meeting here and so I've got to thank

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everyone in the CCE and members of my

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lab for contributing to these projects

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in such a wonderful insightful way and

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also to NSF and NASA Astrobiology for

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we have time for a couple of questions

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for Nick if if you'd like to line up we

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have one here hi I'm Mike Wong from the

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University of Washington I'm really

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intrigued by the idea that the original

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nucleobases could have been different

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from the ones that we see today and I

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was wondering if you've identified any

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plausible reasons why there was a switch

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from those original nucleobases that you

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suggests to the ones that that we find

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in RNA today so one of the principles

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we've also been operating on is with

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respect to the nucleobases we think that

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easy to form nucleosides also translates

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to easy to have them break apart and so

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that's where we see that the the extant

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ones are definitely more stable so one

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reason could be that a transition took

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place to make what is proto RNA one is

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becoming RNA a more stable molecule at

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the nucleo base level also there are

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some reasons if we draw them out that we

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could think about in terms of diversity

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of structures and baking and breaking

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symmetry between the base pairs and the

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minor groove for example that really

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point to the extant ones being superior

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to what we're looking at thank you

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can I ask you a question yeah okay this

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Steve banner sort of is arguing about

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the org that the origin of RNA is a

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solved problem and thinks that it was

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the first prebiotic polymer and I just

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wondering if you could comment I I'm

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gonna accept that that the problem is

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solved or a plausible prebiotic polymer

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when somebody can take ingredients that

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yeah you know I'd say at least a quarter

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of us in the room would say those are

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plausible building blocks and puts it

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through a very simple cycle such as

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hydration dehydration cycles and we can

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do an analysis and we've got oligomers

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that are long enough to fold up and

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maybe show some signs of rudimentary

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evolution when that's done then I'll say

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okay I can accept that what I said

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Lauren was that several of the key

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paradoxes that made it appear as if the

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RNA world model was impossible have been

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resolved what I have now done and I

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mentioned this a couple of minutes ago

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is that there are now when you solve a

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certain set of these paradoxes you

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encounter new ones and so those are the

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ones that are now where focus should be

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directed if you want to develop that as

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I think it were we return hon yeah so

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for the sake of staying on schedule

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Arne yes