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Mutation bias in prokaryotes varies from extreme adenine and thymine (AT) in obligatory endosymbiotic or parasitic bacteria to extreme guanin and cytosin (GC), for instance in actinobacteria. GC bias deeply influences the folding stability of proteins, making proteins less hydrophobic and therefore less stable with respect to unfolding but also less susceptible to misfolding.
We study a model where mutation bias, population size and neutrality influence protein evolution subject to selection for folding stability. We find a non-neutral regime where, for any given population size, there is an optimal mutation bias that maximizes fitness. Interestingly, this optimal GC bias is small for small populations, large for intermediate populations and almost absent (GC~0.5) for large populations. This result is robust with respect to the definition of the fitness function.
Our model suggests that small populations evolving with small GC bias eventually accumulate a significant selective advantage over populations evolving without this bias. This provides a possible explanation to the observation that most, if not all, species adop ting obligatory intracellular lifestyles with a consequent reduction of effective population size shifted their mutation spectrum towards AT. The model similarly predicts that large GC bias is optimal for intermediate population size. To test these predictions we estimated the effective population sizes of bacterial species using the optimal codon usage coefficients computed by dos Reis et al. We found that the population size estimated in this way is significantly smaller for species with small and large GC bias compared to species with no bias, which supports our prediction. |
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