Nikolaev Sergey I, Montoya-Burgos Juan I, Popadin Konstantin, Parand Leila, Margulies Elliott H, Antonarakis Stylianos E
Department of Genetic Medicine and Development, University of Geneva Medical School, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20443-8. doi: 10.1073/pnas.0705658104. Epub 2007 Dec 11.
A comprehensive phylogenetic framework is indispensable for investigating the evolution of genomic features in mammals as a whole, and particularly in humans. Using the ENCODE sequence data, we estimated mammalian neutral evolutionary rates and selective pressures acting on conserved coding and noncoding elements. We show that neutral evolutionary rates can be explained by the generation time (GT) hypothesis. Accordingly, primates (especially humans), having longer GTs than other mammals, display slower rates of neutral evolution. The evolution of constrained elements, particularly of nonsynonymous sites, is in agreement with the expectations of the nearly neutral theory of molecular evolution. We show that rates of nonsynonymous substitutions (dN) depend on the population size of a species. The results are robust to the exclusion of hypermutable CpG prone sites. The average rate of evolution in conserved noncoding sequences (CNCs) is 1.7 times higher than in nonsynonymous sites. Despite this, CNCs evolve at similar or even lower rates than nonsynonymous sites in the majority of basal branches of the eutherian tree. This observation could be the result of an overall gradual or, alternatively, lineage-specific relaxation of CNCs. The latter hypothesis was supported by the finding that 3 of the 20 longest CNCs displayed significant relaxation of individual branches. This observation may explain why the evolution of CNCs fits the expectations of the nearly neutral theory less well than the evolution of nonsynonymous sites.
一个全面的系统发育框架对于研究整个哺乳动物基因组特征的进化，尤其是人类基因组特征的进化而言不可或缺。利用ENCODE序列数据，我们估算了哺乳动物的中性进化速率以及作用于保守编码和非编码元件的选择压力。我们发现中性进化速率可以用世代时间（GT）假说来解释。因此，与其他哺乳动物相比世代时间更长的灵长类动物（尤其是人类），其中性进化速率较慢。受约束元件的进化，尤其是非同义位点的进化，符合分子进化的近中性理论预期。我们表明非同义替换率（dN）取决于一个物种的种群大小。这些结果对于排除易发生超突变的CpG位点是稳健的。保守非编码序列（CNC）的平均进化速率比非同义位点高1.7倍。尽管如此，在真兽类树的大多数基部支系中，CNC的进化速率与非同义位点相似甚至更低。这一观察结果可能是整体逐渐放松或者是CNC在特定谱系中放松的结果。后一种假说得到了以下发现的支持：20个最长的CNC中有3个在个别支系上表现出显著的放松。这一观察结果或许可以解释为什么CNC的进化比非同义位点的进化更不符合近中性理论的预期。
