McShea Hanon, Weibel Catherine, Wehbi Sawsan, Goodman Peter, James Jennifer E, Wheeler Andrew L, Masel Joanna
Department of Earth System Science, Stanford University.
Department of Ecology & Evolutionary Biology, University of Arizona.
bioRxiv. 2024 Jun 22:2023.02.01.526552. doi: 10.1101/2023.02.01.526552.
Nearly neutral theory predicts that species with higher effective population size ( ) are better able to purge slightly deleterious mutations. We compare evolution in high- vs. low- vertebrates to reveal which amino acid frequencies are subject to subtle selective preferences. We take three complementary approaches, two measuring flux and one measuring outcomes. First, we fit non-stationary substitution models of amino acid flux using maximum likelihood, comparing the high- clade of rodents and lagomorphs to its low- sister clade of primates and colugos. Second, we compare evolutionary outcomes across a wider range of vertebrates, via correlations between amino acid frequencies and . Third, we dissect the details of flux in human, chimpanzee, mouse, and rat, as scored by parsimony - this also enables comparison to a historical paper. All three methods agree on which amino acids are preferred under more effective selection. Preferred amino acids tend to be smaller, less costly to synthesize, and to promote intrinsic structural disorder. Parsimony-induced bias in the historical study produces an apparent reduction in structural disorder, perhaps driven by slightly deleterious substitutions. Within highly exchangeable pairs of amino acids, arginine is strongly preferred over lysine, and valine over isoleucine, consistent with more effective selection preferring a marginally larger free energy of folding. These two preferences match differences between thermophiles and mesophilic relatives. These results reveal the biophysical consequences of mutation-selection-drift balance, and demonstrate the utility of nearly neutral theory for understanding protein evolution.
近中性理论预测，有效种群规模（ ）较大的物种能够更好地清除轻度有害突变。我们比较了高 与低 脊椎动物的进化情况，以揭示哪些氨基酸频率受到细微的选择偏好影响。我们采用了三种互补方法，两种测量通量，一种测量结果。首先，我们使用最大似然法拟合氨基酸通量的非平稳替代模型，将啮齿动物和兔形目动物的高 进化枝与其灵长类动物和鼯猴的低 姐妹进化枝进行比较。其次，我们通过氨基酸频率与 之间的相关性，比较了更广泛脊椎动物的进化结果。第三，我们剖析了人类、黑猩猩、小鼠和大鼠中通量的细节，通过简约法进行评分——这也便于与一篇历史论文进行比较。所有三种方法在更有效选择下哪种氨基酸更受青睐这一点上达成了一致。受青睐的氨基酸往往更小，合成成本更低，并且会促进内在结构无序。历史研究中由简约法引起的偏差导致结构无序明显减少，这可能是由轻度有害替代驱动的。在高度可互换的氨基酸对中，精氨酸比赖氨酸更受强烈青睐，缬氨酸比异亮氨酸更受青睐，这与更有效选择偏好略大的折叠自由能一致。这两种偏好与嗜热菌和中温亲属之间的差异相匹配。这些结果揭示了突变 - 选择 - 漂变平衡的生物物理后果，并证明了近中性理论在理解蛋白质进化方面的实用性。
