A Model for the Evolution of Nucleotide Polymerase Directionality

Background: In all known living organisms, every enzyme that synthesizes nucleic acid polymers does so by adding nucleotide 59-triphosphates to the 39-hydroxyl group of the growing chain. This results in the well known 5’?3’ directionality of all DNA and RNA Polymerases. The lack of any alternative mechanism, e.g. addition in a 3’?5 ’ direction, may indicate a very early founder effect in the evolution of life, or it may be the result of a selective pressure against such an alternative. Methodology/Principal Findings: In an attempt to determine whether the lack of an alternative polymerase directionality is the result of a founder effect or evolutionary selection, we have constructed a basic model of early polymerase evolution. This model is informed by the essential chemical properties of the nucleotide polymerization reaction. With this model, we are able to simulate the growth of organisms with polymerases that synthesize either 5’?3 ’ or 3’?5 ’ in isolation or in competition with each other. Conclusions/Significance: We have found that a competition between organisms with 5’?3 ’ polymerases and 3’?5’ polymerases only results in a evolutionarily stable strategy under certain conditions. Furthermore, we have found that mutations lead to a much clearer delineation between conditions that lead to a stable coexistence of these populations and conditions which ultimately lead to success for the 5’?3 ’ form. In addition to presenting a plausible explanation for th

Competition during exponential growth at various temperatures, with no mutations.

<p>The model system was seeded with environments, at simulation temperatures of 0.10, 0.30, 0.40, or 0.60, containing 100 organisms, 50 each with forward and reverse polymerases, with a 5.5 average polymerase rate. <b>A</b>. Population size of model organisms as a function of simulation time. <b>B</b>. Evolution of the average polymerase rate for the organisms in each environment as a function of simulation time. In each case, solid lines are used to indicate environments with forward polymerizing organisms and dashed lines are for reverse polymerizing organisms. For every simulation mutations were disallowed. Different temperatures are indicated with different data markers as indicated in the figure legend, and are expressed in units of .</p

Exponential growth at various temperatures in the absence of competition, with mutations.

<p>The model system was seeded with environments, at simulation temperatures of 0.10, 0.30, 0.40, or 0.60, containing 10 organisms with a 5.5 average polymerase rate. <b>A</b>. Population size of model organisms as a function of simulation time. <b>B</b>. Evolution of the average polymerase rate for the organisms in each environment as a function of simulation time. In each case, solid lines are used to indicate environments with forward polymerizing organisms and dashed lines are for reverse polymerizing organisms. Different temperatures are indicated with different data markers as indicated in the figure legend, and are expressed in units of .</p

Competition in an environment at maximum capacity, with mutations.

<p>Environments, at simulation temperatures of 0.10, 0.30, 0.40, or 0.60, were seeded with 500 organisms containing forward polymerases and 500 containing reverse, both with a 5.5 average polymerase rate. <b>A</b>. Population size of model organisms as a function of simulation time. <b>B</b>. Evolution of the average polymerase rate for the organisms in each environment as a function of simulation time. In each case, solid lines are used to indicate environments with forward polymerizing organisms and dashed lines are for reverse polymerizing organisms. Different temperatures are indicated with different data markers as indicated in the figure legend, and are expressed in units of .</p

Generational change in polymerase rate as a function of temperature.

<p>The organisms from the systems plotted in 1 were analyzed for the difference between the rate of their polymerase and the rate of their parent's polymerase. This difference is plotted for the various different temperatures simulated. The maximal difference we would expect to see (i.e. in the case that inheritance was purely random) would be 5.</p

Competition in an environment at maximum capacity at various temperatures.

<p>Simulations were carried out with environments at temperatures ranging from 0.10 to 0.60 in 0.05 increments. In each simulation, the environment was seeded at full capacity with 500 organisms containing forward polymerases and 500 containing reverse. For each variety there were 50 organisms with each of the possible polymerase rates, giving an average rate of 5.5 In <b>A</b> and <b>B</b> the natural log of the population of organisms containing reverse polymerases is plotted as a function of simulation time. <b>A</b> is the data from simulations where mutation was allowed, and <b>B</b> is from simulations where mutations were not permitted. A plot of the slopes of a least squares regression line for the data in each simulations is plotted as a function of simulation temperature. Data from simulations with mutation is plotted as the solid line with data from the no mutation simulations plotted as a dashed line.</p

Exponential growth at various temperatures in the absence of competition, with no mutations.

<p>The model system was seeded with environments, at simulation temperatures of 0.10, 0.30, 0.40, or 0.60, containing 10 organisms with a 5.5 average polymerase rate. <b>A</b>. Population size of model organisms as a function of simulation time. <b>B</b>. Evolution of the average polymerase rate for the organisms in each environment as a function of simulation time. In each case, solid lines are used to indicate environments with forward polymerizing organisms and dashed lines are for reverse polymerizing organisms. For every simulation mutations were disallowed. Different temperatures are indicated with different data markers as indicated in the figure legend, and are expressed in units of .</p

Competition during exponential growth at various temperatures, with mutations.

<p>The model system was seeded with environments, at simulation temperatures of 0.10, 0.30, 0.40, or 0.60, containing 100 organisms, 50 each with forward and reverse polymerases, with a 5.5 average polymerase rate. <b>A</b>. Population size of model organisms as a function of simulation time. <b>B</b>. Evolution of the average polymerase rate for the organisms in each environment as a function of simulation time. In each case, solid lines are used to indicate environments with forward polymerizing organisms and dashed lines are for reverse polymerizing organisms. Different temperatures are indicated with different data markers as indicated in the figure legend, and are expressed in units of .</p

Competition in an environment at maximum capacity, with no mutations.

<p>Environments, at simulation temperatures of 0.10, 0.30, 0.40, or 0.60, were seeded with 500 organisms containing forward polymerases and 500 containing reverse, both with a 5.5 average polymerase rate. <b>A</b>. Population size of model organisms as a function of simulation time. <b>B</b>. Evolution of the average polymerase rate for the organisms in each environment as a function of simulation time. In each case, solid lines are used to indicate environments with forward polymerizing organisms and dashed lines are for reverse polymerizing organisms. For every simulation mutations were disallowed. Different temperatures are indicated with different data markers as indicated in the figure legend, and are expressed in units of .</p