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Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations

机译：突变偏见在小群体演变中有利于蛋白质折叠稳定性

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Mutation bias in prokaryotes varies from extreme adenine and thymine (AT) in obligatory endosymbiotic or parasitic bacteria to extreme guanine and cytosine (GC), for instance in actinobacteria. GC mutation bias deeply influences the folding stability of proteins, making proteins on the average less hydrophobic and therefore less stable with respect to unfolding but also less susceptible to misfolding and aggregation. We study a model where proteins evolve subject to selection for folding stability under given mutation bias, population size, and neutrality. 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 usage is small for small populations, large for intermediate populations and around 50% for large populations. This result is robust with respect to the definition of the fitness function and to the protein structures studied. Our model suggests that small populations evolving with small GC usage eventually accumulate a significant selective advantage over populations evolving without this bias. This provides a possible explanation to the observation that most species adopting obligatory intracellular lifestyles with a consequent reduction of effective population size shifted their mutation spectrum towards AT. The model also predicts that large GC usage 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. and the synonymous to non-synonymous substitution ratio computed by Daubin and Moran. We found that the population sizes estimated in these ways are significantly smaller for species with small and large GC usage compared to species with no bias, which supports our prediction.
机译：原核生物中的突变偏见从强制性内嗜血或寄生虫细菌中的极端腺嘌呤和胸腺嘧啶（AT）变化，以极端的鸟嘌呤和胞嘧啶（GC），例如在actinobacteria中。 GC突变偏差深深地影响蛋白质的折叠稳定性，使蛋白质在较小的疏水性较小，因此相对于展开的较小稳定性，但也易于易错和聚集。我们研究了蛋白质在给定突变偏差，人物大小和中立性下进行折叠稳定性的选择。我们发现一个非中性的制度，对于任何给定的人的大小，有一个最佳的突变偏压，最大化健康。有趣的是，这种最佳GC使用率对于小人群而言，对于中间人群而大，而大人群的50岁左右。对于对健身功能的定义和研究的蛋白质结构，该结果是稳健的。我们的模型表明，与小型GC使用情况的小群体最终积累了在没有这种偏见的情况下在演变的群体中积累了显着的选择性优势。这提供了对观察结果的可能解释，即大多数采用强制性细胞内的生活方式的大多数物种，随后降低有效群体大小的突变将其突变谱移向左右。该模型还预测，对于中间人口大小，大型GC使用率是最佳的。为了测试这些预测，我们使用DOS REIS等人计算的最佳密码子使用系数估计了细菌种类的有效种群尺寸。和Daubin和Moran计算的非同义替代率的同义词。我们发现，与没有偏差的物种相比，在这些方式估计的人口尺寸估计的种类小而大的GC使用率，这是不支持我们的预测。

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