Comeron Josep M
Department of Biological Sciences, University of Iowa, 212 Biology Building, Iowa City, IA 52242, USA.
Proc Natl Acad Sci U S A. 2006 May 2;103(18):6940-5. doi: 10.1073/pnas.0510638103. Epub 2006 Apr 21.
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.
最近的大规模基因组和进化研究揭示了在哺乳动物进化过程中，同义突变受到弱选择的微小但可检测到的特征，这种选择可能作用于翻译效率层面（即翻译选择）。为了研究弱选择，特别是翻译选择，是否在塑造当今人类群体中存在的同义突变的命运方面发挥任何作用，我们研究了人类与黑猩猩分离后人类谱系中多态性水平的遗传变异和进化模式。我们发现有证据表明中性机制正在影响人类中多态性突变的频率。我们的结果表明，在所有等密度区都观察到最近向AT的突变倾向增加，这导致AT突变以比GC突变更低的频率分离。然而，总体而言，突变倾向的变化和其他中性情况不足以解释同义突变与非编码突变之间的差异，或在翻译选择模型下潜在有利或有害的同义突变之间的差异。此外，对同义突变选择强度的几个估计都表明，在翻译选择层面存在弱选择的可检测影响。因此，随机遗传漂变、最近突变倾向的变化以及弱选择都会影响当今作为多态性存在的同义突变的命运。在进化分析中，往往假定突变倾向恒定且同义突变完全中性，而所有这些中性和选择性特征都应予以考虑。
