Accelerated rate of gene gain and loss in primates
Accelerated rate of gene gain and loss in primates
复制标题
DOI：
10.1534/genetics.107.080077
复制
发表时间：
2007-11-01
期刊：
影响因子：
3.3
通讯作者：
Han, Sang-Gook
中科院分区：
文献类型：
--
作者：
Hahn, Matthew W.;Demuth, Jeffery P.;Han, Sang-Gook
负责现代人类进化的分子变化主要是根据调节或蛋白质编码序列中的单个核苷酸替换来讨论的。然而，灵长类动物的核苷酸替换速率较慢，因此人类和黑猩猩在核苷酸水平上非常相似。我们发现，相对于其他哺乳动物，灵长类动物的分子进化的第三个来源——基因的获得和丧失——是加速的。使用一种新的方法，可以估计谱系之间的速率异质性，我们发现人类的基因周转率比其他哺乳动物快2.5倍以上，这可能是由于突变和选择的力量。通过协调分析中包含的所有基因家族的基因树，我们能够独立验证推断的重复数量。我们还使用了两种基于恒河猴基因组组装的方法来进一步验证我们的结果。我们的分析发现，即使考虑到灵长类动物的总体速度加速，几个基因家族的扩张或收缩速度也比预期的要快，包括人类大脑相关家族的大小增加了一倍多。许多表现出大规模扩张的家族也显示出其核苷酸序列上的正选择的证据，这表明选择在形成哺乳动物之间拷贝数差异方面起着重要作用。这些发现可能有助于解释为什么人类和黑猩猩在同源核苷酸之间表现出高度相似性，而在形态和行为上却存在巨大差异。
The molecular changes responsible for the evolution of modern humans have primarily been discussed in terms of individual nucleotide substitutions in regulatory or protein coding sequences. However, rates of nucleotide substitution are slowed in primates, and thus humans and chimpanzees are highly similar at the nucleotide level. We find that a third source of molecular evolution, gene gain and loss, is accelerated in primates relative to other mammals. Using a novel method that allows estimation of rate heterogeneity among lineages, we find that the rate of gene turnover in humans is more than 2.5 times faster than in other mammals and may be due to both mutational and selective forces. By reconciling the gene trees for all of the gene families included in the analysis, we are able to independently verify the numbers of inferred duplications. We also use two methods based on the genome assembly of rhesus macaque to further verify our results. Our analyses identify several gene families that have expanded or contracted more rapidly than is expected even after accounting for an overall rate acceleration in primates, including brain-related families that have more than doubled in size in humans. Many of the families showing large expansions also show evidence for positive selection on their nucleotide sequences, suggesting that selection has been important in shaping copy number differences among mammals. These findings may help explain why humans and chimpanzees show high similarity between orthologous nucleotides yet great morphological and behavioral differences.