Genome-wide search of gene conversions in duplicated genes of mouse and rat
Genome-wide search of gene conversions in duplicated genes of mouse and rat
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DOI：
10.1093/molbev/msj093
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发表时间：
2006-05-01
影响因子：
10.7
通讯作者：
Saitou, N
中科院分区：
文献类型：
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作者：
Ezawa, K;OOta, S;Saitou, N
基因转换被认为在多基因家族的同质化和等位基因的多样化等基因组组成的形成中起着重要作用。我们设计了两个四元组的统计检验来检测基因转换事件。每个“四重奏”由两对同源序列组成，这两对序列被认为是由两个密切相关物种的复制事件和随后的物种形成产生的。作为示例数据，使用EnSembl小鼠和大鼠的cdna序列来获得基因转换事件的全基因组图像。我们对2641个四重奏进行了广泛的采样，这些四重奏似乎是在灵长类和啮齿动物分化之后和老鼠-老鼠物种形成之前的重复造成的。我们的新测试与Sawyer‘s和Takahata的测试相结合，在保持尽可能少的假阳性的同时提高了检测灵敏度。使用这一联合检测显示，约18%(488个四倍体)的基因转换高度阳性。在这些序列中，有340个(占总数的13%)在小鼠序列对中显示出基因转换的迹象。这些基因转化阳性的基因对大多连锁在同一染色体上，连锁和非连锁类别中阳性对的比例分别为15%和1%。统计分析表明：(1)基因转换的敏感性与物理距离呈负相关，特别是在距离小于55kb的基因对中观察到29%的频率；(2)基因转换的发生不取决于转录方向；(3)由3到6个相邻基因组成的小基因家族非常容易进行基因转换；(4)基因转换的频率因功能类别的不同而有很大差异，钙粘附素有利于基因转换，而犁鼻受体1型和免疫球蛋白V型蛋白不利于基因转换。这些发现将有助于加深对基因转化作用的理解。
Gene conversion is considered to play important roles in the formation of genomic makeup such as homogenization of multigene families and diversification of alleles. We devised two statistical tests on quartets for detecting gene conversion events. Each "quartet" consists of two pairs of orthologous sequences supposed to have been generated by a duplication event and a subsequent speciation of two closely related species. As example data, EnsEMBL mouse and rat cDNA sequences were used to obtain a genome-wide picture of gene conversion events. We extensively sampled 2,641 quartets that appear to have resulted from duplications after the divergence of primates and rodents and before mouse-rat speciation. Combination of our new tests with Sawyer's and Takahata's tests enhanced the detection sensitivity while keeping false positives as few as possible. About 18% (488 quartets) were shown to be highly positive for gene conversion using this combined test. Out of them, 340 (13% of the total) showed signs of gene conversion in mouse sequence pairs. Those gene conversion-positive gene pairs are mostly linked in the same chromosomes, with the proportion of positive pairs in the linked and unlinked categories being 15% and 1%, respectively. Statistical analyses showed that (1) the susceptibility to gene conversion correlates negatively with the physical distance, especially the frequency of 29% was observed for gene pairs whose distances are smaller than 55 kb; (2) the occurrence of gene conversions does not depend on the transcriptional direction; (3) small gene families consisting of between three and six contiguous genes are highly prone to gene conversion; and (4) frequency of gene conversions greatly varies depending on functional categories, and cadherins favor gene conversion, while vomeronasal receptors type 1 and immunoglobulin V-type proteins disfavor it. These findings will be useful to deepen the understanding of the roles of gene conversion.