Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans
Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans
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DOI：
10.1073/pnas.0510638103
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发表时间：
2006-05-02
影响因子：
11.1
通讯作者：
Comeron, JM
中科院分区：
文献类型：
--
作者：
Comeron, JM
最近的大规模基因组和进化研究揭示了哺乳动物进化过程中同义突变的弱选择特征，可能作用于翻译效率(即翻译选择)水平。为了研究弱选择，特别是翻译选择是否在决定目前存在于人类种群中的同义突变的命运方面发挥了作用，我们研究了多态水平上的遗传变异和人与黑猩猩分离后人类谱系的进化模式。我们发现有证据表明，中性机制正在影响人类多态突变的频率。我们的结果表明，最近在所有等位基因中观察到的AT突变倾向的增加，这是导致AT突变以低于GC突变的频率分离的原因。然而，总的来说，突变倾向和其他中性情景的变化不足以解释同义突变和非编码突变之间的差异，或者同义突变之间的差异，在翻译选择模型下，同义突变可能有利或有害。此外，对同义突变的选择强度的几种估计都表明弱选择在翻译选择水平上具有可检测到的影响。因此，随机遗传漂移、最近突变趋势的变化和弱选择影响着同义突变的命运，这些突变今天被认为是多态的。在进化分析中，所有这些中性和选择性的特征都应该被考虑在内，这些进化分析往往假设突变趋势是恒定的，同义突变是完全中立的。
Recent large-scale genomic and evolutionary studies have revealed the small but detectable signature of weak selection on synonymous mutations during mammalian evolution, likely acting at the level of translational efficacy (i.e., translational selection). To investigate whether weak selection, and translational selection in particular, plays any role in shaping the fate of synonymous mutations that are present today in human populations, we studied genetic variation at the polymorphic level and patterns of evolution in the human lineage after human-chimpanzee separation. We find evidence that neutral mechanisms are influencing the frequency of polymorphic mutations in humans. Our results suggest a recent increase in mutational tendencies toward AT, observed in all isochores, that is responsible for AT mutations segregating at lower frequencies than GC mutations. In all, however, changes in mutational tendencies and other neutral scenarios are not sufficient to explain a difference between synonymous and noncoding mutations or a difference between synonymous mutations potentially advantageous or deleterious under a translational selection model. Furthermore, several estimates of selection intensity on synonymous mutations all suggest a detectable influence of weak selection acting at the level of translational selection. Thus, random genetic drift, recent changes in mutational tendencies, and weak selection influence the fate of synonymous mutations that are present today as polymorphisms. All of these features, neutral and selective, should be taken into account in evolutionary analyses that often assume constancy of mutational tendencies and complete neutrality of synonymous mutations.