Physicochemical amino acid properties better describe substitution rates in large populations
Physicochemical amino acid properties better describe substitution rates in large populations
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DOI：
10.1101/378893
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发表时间：
2018-08
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影响因子：
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通讯作者：
Claudia C. Weber;S. Whelan
中科院分区：
文献类型：
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作者：
Claudia C. Weber;S. Whelan
已知化学上远距离的氨基酸之间的取代发生的频率低于更相似的氨基酸之间的取代。然而，这种知识并没有反映在大多数密码子替换模型中，这些模型将所有非同义变化视为就对蛋白质的影响而言是等同的。已经提出了将化学距离整合到模型中的各种方法，其中一种常见的方法是将取代分为激进或保守类别。然而，目前还不清楚所产生的模型是否比简单的模型更好地描述了序列进化。我们提出了一个参数密码子模型，区分激进和保守的取代，使我们能够评估，如果激进的取代优先删除的选择。将我们的新模型应用于一系列的基因组数据，我们发现区分激进和保守取代为大群体提供了更好的拟合，但对于较小的群体没有同等的改善。使用这些相同的数据比较密码子和氨基酸模型表明，从大的人口的比对往往选择系统发育模型包含有关氨基酸交换性的信息，而遗传密码的结构是更重要的较小的人口。我们的研究结果表明，对自由基取代的选择，平均而言，更明显的大群体比小的。在较小的群体中，可观察到的选择效应减少可能是由于更强的遗传漂变使检测偏好更具挑战性。我们的研究结果意味着一个系统发育组的生活史和模型，最好地描述其演变之间的重要联系。
Substitutions between chemically distant amino acids are known to occur less frequently than those between more similar amino acids. This knowledge, however, is not reflected in most codon substitution models, which treat all non-synonymous changes as if they were equivalent in terms of impact on the protein. A variety of methods for integrating chemical distances into models have been proposed, with a common approach being to divide substitutions into radical or conservative categories. Nevertheless, it remains unclear whether the resulting models describe sequence evolution better than their simpler counterparts. We propose a parametric codon model that distinguishes between radical and conservative substitutions, allowing us to assess if radical substitutions are preferentially removed by selection. Applying our new model to a range of phylogenomic data, we find differentiating between radical and conservative substitutions provides significantly better fit for large populations, but see no equivalent improvement for smaller populations. Comparing codon- and amino acid models using these same data shows that alignments from large populations tend to select phylogenetic models containing information about amino acid exchangeabilities, whereas the structure of the genetic code is more important for smaller populations. Our results suggest selection against radical substitutions is, on average, more pronounced in large populations than smaller ones. The reduced observable effect of selection in smaller populations may be due to stronger genetic drift making it more challenging to detect preferences. Our results imply an important connection between the life history of a phylogenetic group and the model that best describes its evolution.