Evolutionary Pattern of Gene Homogenization between Primate-Specific Paralogs after Human and Macaque Speciation Using the 4-2-4 Method

Evolutionary Pattern of Gene Homogenization between Primate-Specific Paralogs after Human and Macaque Speciation Using the 4-2-4 Method
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DOI:
10.1093/molbev/msq109
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发表时间:
2010-09-01
影响因子:
10.7
通讯作者:
Saitou, Naruya
Saitou, Naruya
中科院分区:
生物学1区
文献类型:
--
作者:
Ezawa, Kiyoshi;Ikeo, Kazuho;Saitou, Naruya

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重复基因的同质化是基因家族进化的重要因素。在以前的研究中,我们开发了一种方法,命名为4-2-4,检测部分同质化具有高灵敏度和高特异性使用四元组。四联体是由一个复制事件和随后的两个密切相关物种的物种形成所产生的一组四个基因。我们搜索了人类和猕猴的基因组,发现了430个非冗余的四联体,对应于灵长类动物特有的旁系同源物。同质化的发生率为10.0%(43/430),约为10.0%(43/430)。三分之一(29.8% = 206/691)的啮齿动物特异性非冗余四联体通过比较小鼠和大鼠基因组获得。这种差异的一部分来自于灵长类动物的旁系亲属往往比啮齿类动物的旁系亲属更远,其余的可能是灵长类动物和啮齿类动物谱系之间中性进化速率的固有差异。考虑到假阴性影响的统计分析揭示了灵长类和啮齿类动物中序列差异和同质化流行率之间的负相关性。控制假阴性率和序列差异的进一步统计分析揭示了灵长类和啮齿类旁系同源物共有的两个特征; 1)均质化流行率与物理距离的显著负相关,以及2)流行率与相对转录方向之间没有显著相关性。人类-猕猴四联体的基因组比对中的均质化模式表明,基因转换,而不是不平等的交换,是均质化的主要原因。
Homogenization of duplicated genes is an important factor for gene family evolution. In the previous study, we developed a method, named 4-2-4 here, to detect partial homogenization with high sensitivity and high specificity using quartets. A quartet is a set of four genes generated by a duplication event and the subsequent speciation of two closely related species. We searched the human and macaque genomes and found 430 nonredundant quartets, which correspond to primate-specific paralogs. The prevalence of homogenization in these quartets was 10.0% (43/430), which was ca. one-third of that (29.8% = 206/691) in the rodent-specific nonredundant quartets obtained through comparison of mouse and rat genomes. Part of this difference comes from the fact that primate paralogs tend to be more remotely located to each other than rodent paralogs, and the remainder may be explained by the inherent difference in the neutral evolutionary rate between the primate and rodent lineages. A statistical analysis taking account of the effects of false negatives uncovered negative correlations between sequence divergence and homogenization prevalence both in primates and rodents. Further statistical analyses controlling for false-negative rates and sequence divergences revealed two characteristics shared by the primate and rodent paralogs; 1) significant negative correlations of the homogenization prevalence with physical distances, and 2) no significant correlation between the prevalence and relative transcriptional orientations. Patterns of the homogenization in the genomic alignments of human-macaque quartets indicate that gene conversion, rather than unequal crossing-over, is the major cause of the homogenization.