Berglund Jonas, Pollard Katherine S, Webster Matthew T
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
PLoS Biol. 2009 Jan 27;7(1):e26. doi: 10.1371/journal.pbio.1000026.
Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (dN/dS) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.
在近期进化过程中，人类谱系上经历了加速进化速率的基因是参与人类特异性适应的候选基因。为了确定导致某些基因进化速率增加的力量，我们分析了10238个人类基因与其在黑猩猩和猕猴中的直系同源基因的比对。使用似然比检验，我们确定了沿着人类谱系碱基替换速率加速的蛋白质编码序列。在人类中快速进化的外显子有显著的倾向包含从AT到GC（从弱到强）偏向性替换的簇。在快速进化外显子侧翼的非编码序列中也观察到这种模式。加速进化的外显子出现在男性重组率升高的区域，并且相对于基因组平均值表现出过量的非同义替换。接下来，我们分析了沿着人类谱系非同义与同义碱基替换率（dN/dS）显著升高的基因，以及相对于人类多态性有过量氨基酸替换替换的基因。这些基因也显示出从弱到强偏向性替换簇的证据。这些发现表明，一个与重组相关的过程，如偏向性基因转换（BGC），正在推动人类基因组中GC等位基因的固定。这个过程可以导致编码序列的加速进化和过量的氨基酸替换替换，从而为正选择测试产生显著结果。
