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hello my name is yuta a takagi

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and this presentation will be on using

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digital life simulations

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to examine the evolutionary origin of

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cellularity and metabolism

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in this research we designed and coded a

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digital life system to study evolution

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and used the simulation to study the

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origin of cellularity

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first a bit of background we know that

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the last universal common ancestor was

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already cellular

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because cell membrane proteins such as

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signal receptors and the

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atp synthase motor are universally

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present across the known tree of life

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however almost all origin of life

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hypotheses suggest a non-cellular

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beginning

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such as the rna world hypothesis where

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the first entities were self-replicating

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rnas

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or in the auto catalytic network

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hypothesis

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which more closely resembles complex

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this necessarily means that at some

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point in early life

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there was a transition from non-cellular

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to cellular entities

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our work was motivated by the fact that

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even though there has been a lot of

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previous research on the biochemistry of

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early cellularity

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there has been very little research

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examining the evolutionary causes for

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i will now give a simplified explanation

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of the simulation

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the simulation consists of a population

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of replicators referred to as

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organisms in a shared environment

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containing food

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the environment is capped at a certain

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population size

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each organism has a genome composed of

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metabolic and cellularity genes

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metabolic genes represent logical not

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and gates

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that denote a boolean logic gate network

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the food in the simulations

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are boolean logic puzzles that give

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energy as a reward

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depending on how well they are solved by

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the genome's logic gate network

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a property we have termed metabolic

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energy is stored in the organism and is

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used to read through the genome

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where each step corresponds to one gene

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denoting a calculation in the boolean

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logic gate network

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the genome can read values from the

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puzzle's input register

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process the values through its logic

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gate network

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and rate the solutions to an output

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register which is then compared to the

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puzzle's solution register

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to determine the energy reward based on

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the number of correctly solved digits

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if stored energy runs out the organism

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cellularity genes are logically neutral

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in the boolean gate network

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but instead determine an organism's

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level of cellularity

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cellularity is defined as a value

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between zero

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and one with a zero representing

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non-cellular

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and one representing completely cellular

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in other words entirely closed off

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cellularity genes confer cellularity

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according to the equation one minus

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one-half to the x

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where x is the number of cellularity

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genes in the genome

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asymptotically approaching one with

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higher numbers of cellularity genes

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organisms with low levels of cellularity

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are more open to the environment

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and are subject to losing or gaining

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genetic material

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or free energy from the environment

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while organisms with high cellularity

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the organisms replicate their genomes

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and split into two new identical

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entities

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when a certain level of excess energy is

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reached

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with each new daughter organism

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receiving half of their parents energy

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organisms are constantly subject to low

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levels of mutation

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in the form of small alterations to the

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genome through insertion or deletion of

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metabolic or cellularity genes

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or through small reconfigurations of the

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organisms are also subject to loss or

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gain of potentially large

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sections of genetic material through

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horizontal gene transfer

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depending on their level of cellularity

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this form of mutation can cause drastic

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changes to the metabolic network

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and we have found that this is almost

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always deleterious to the metabolic

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the simulation is quite far abstracted

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from biological life

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but it does represent a system capable

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of real evolution

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where cellularity and metabolic

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proficiency are dependent variables

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allowing us to empirically address broad

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evolutionary questions

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after development of the software was

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completed we needed to narrow down the

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parameter space to conditions that

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allowed for organisms to survive and

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evolve

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during this stage we noticed that the

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amount of free energy in the environment

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had an effect on cellularity

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this observation led to our primary

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hypothesis

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that non-cellularity will be selectively

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advantageous

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when simple sources of energy are freely

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available in the environment

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and conversely that high cellularity

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will be selectively advantageous

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when only complex food sources are

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in order to test these hypotheses we ran

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a series of selection experiments

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altering the organism's

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starting cellularity and the amount of

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free energy in the environment

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simulation sets a and b began with zero

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cellularity genes giving initial

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cellularity values of zero percent

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while such c and d began with three

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cellularity genes giving 87.5 percent

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cellularity

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simulation such a and c were provided

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environments with

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unlimited food and unlimited energy

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while sets b

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and d had unlimited food but limited

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energy

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each condition was run with three

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replicas each

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under three maximum population settings

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of five hundred one thousand

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we found that regardless of the starting

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cellularity organisms consistently

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evolved towards low cellularity

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under high environmental energy

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conditions and high cellularity under

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low environmental energy conditions

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we further saw a corresponding trend

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towards low and high metabolic

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proficiency

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with poor solutions evolving under high

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environmental energy conditions and good

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solutions

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evolving under low environmental energy

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conditions

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we statistically confirmed this

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correlation between cellularity and

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metabolism

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showing that they are indeed co-evolving

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with the population average values for

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simulation set b

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taken at 250 step intervals showing a

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linear regression with a p-value

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this seems to make sense mechanistically

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if you think about it

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when easy-to-use resources are plentiful

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in the environment it makes

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sense to be more open to that

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environment and there is

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little selective advantage for complex

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metabolism

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moreover large inconsistent genomic

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alterations prevent the darwinian

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evolution

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of complex metabolism on the other hand

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in environments lacking such resources

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there is a high selective advantage for

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complex metabolisms

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capable of utilizing difficult to use

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resources

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this provides selective pressure for a

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more closed-off entity

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both in order to retain the metabolic

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products of that complex metabolism

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and to maintain genetic fidelity by

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i believe this also presents a mechanism

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for a darwinian transition

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where the availability of free energy

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drives a change in cellularity that is

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coupled with replication fidelity

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which is a necessary condition for the

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evolution of metabolism

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although full disclosure this

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interpretation is still a point of

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debate between my research collaborators

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so to summarize most scholars agree that

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life began in a geochemically rich

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environment whether that be hydrothermal

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vents

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tidal pools or any manner of prebiotic

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soup scenario

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our research adds to the understanding

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of life's origins

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by showing that cellularity likely arose

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in response to a

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change towards a less rich environment

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perhaps through some geological event

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or perhaps simply through the depletion

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our simulation research suggests that

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any geochemically rich origin of life

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setting

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would have prevented the evolution of

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cellular life

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replicators with access to plentiful

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prebiotic precursor molecules

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have an evolutionary incentive not to

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partition themselves

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we also found that cellularity and

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metabolism would have co-evolved

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in response to resource limitation

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cellularity provides a replicator

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greater protection from mutation

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allowing for a complex metabolism

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to evolve giving it access to previously

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non-useful resources

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cellularity also prevents the products

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of metabolic processing

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to be lost to the environment this gives

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a strong evolutionary incentive for

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complex metabolism to evolve

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when easy to utilize resources are

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exhausted

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which in turn applies an evolutionary

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pressure towards concurrently evolving

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cellularity

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these mechanisms suggest that the

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evolution of both

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metabolism and cellularity in early

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terrestrial life

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would have occurred in response to a

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change in the geochemical setting of

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life's origin

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from an environment rich in prebiotic

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precursor molecules

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to a poorer environment while any number

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of mechanisms

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could explain a change in the

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geochemical setting of early life

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a simple scenario suggests itself where

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in an initially rich environment

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becomes depleted as replicators grow in

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population

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driving the shift towards more complex

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metabolic processes

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lastly i propose a mechanism for a shift

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from a non-darwinian to darwinian system

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a so-called darwinian transition

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cellularity provides a replicator with

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greater protection from mutation

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with low mutation rates being a

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necessary condition for darwinian

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evolution of the genome to occur

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as such the very capacity for the genome

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to evolve in a darwinian manner

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may be subject to selection through

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cellularity

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and by extension the plenitude or

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scarcity of resources in the environment

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we present a driving mechanism for a

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darwinian transition

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in conclusion we found that cellularity

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and complex metabolism

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are not an inevitable outcome of

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evolution

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but rather they are linked traits that

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are reversibly selected for

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by the environmental availability of

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resources

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cellularity and complex metabolism in

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early earth-based

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life likely evolved in response to a

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changing geochemical environment

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and facilitated life's capacity for

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darwinian evolution

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thank you for your attention and

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interest in this work

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if you are further interested this

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research was published in greater detail

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in the journal of molecular evolution if

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you are interested in using the

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simulation or contributing to the

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software

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it is publicly available on github if

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you have

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any further questions or comments please

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feel free to contact me at utaatakagi

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gmail.com i would like to acknowledge my

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collaborators in this research

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diaper new yen dr tom wexler and dr

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aaron goldman

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this research was enabled by the oberlin

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college department of biology and

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funding was provided by the national

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aeronautics and space administration