Timing of Replication Is a Determinant of Neutral Substitution Rates but Does Not Explain Slow Y Chromosome Evolution in Rodents
Timing of Replication Is a Determinant of Neutral Substitution Rates but Does Not Explain Slow Y Chromosome Evolution in Rodents
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DOI：
10.1093/molbev/msp314
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发表时间：
2010-05-01
影响因子：
10.7
通讯作者：
Hurst, Laurence D.
中科院分区：
文献类型：
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作者：
Pink, Catherine J.;Hurst, Laurence D.
突变率，作为假定的中性位点的替换率，在哺乳动物基因组中是高度可变的：基因之间、常染色体之间以及X、Y和常染色体之间存在异质性。X、Y和常染色体之间的差异通常被认为反映了雄性生殖系中更多的细胞分裂。这种效应既不能解释常染色体内的差异，也不能预测在啮齿类动物中观察到的X、Y和常染色体之间的差异。最近有人提出，在灵长类动物中，S阶段基因复制的时间是中性进化速度的重要决定因素。在这里，我们问1)我们是否可以在啮齿动物身上复制这一结果，2)不同的常染色体是否在不同的时间平均复制，以及3)这是否可能解释它们的替换率的差异。最后，我们问4)X、Y和常染色体是否在不同的时间复制，以及5)是否有任何差异可以解释为什么复制事件的数量本身不能解释它们的替换率。我们发现，与灵长类动物一样，常染色体内含子的进化速度在S期显著增加。不同的常染色体确实有不同的平均复制时间，与重排一起，这是常染色体之间替换率差异的显著预测因素。虽然我们发现常染色体、X连锁和Y连锁的基因在不同的时间复制，但矛盾的是，Y连锁的基因复制最晚，复制更频繁，但进化不是特别快。这些结果支持这一假说，即复制时机是替换率异质性的重要来源。
Mutation rates, assayed as substitution rates of putatively neutral sites, are highly variable around mammalian genomes: There is heterogeneity between genes, between autosomes, and between X, Y, and autosomes. The differences between X, Y, and autosomes are typically assumed to reflect the greater number of cell divisions in the male germ-line. Such an effect can neither account for within-autosome differences nor does it predict the differences between X, Y, and autosome observed in rodents. It has recently been proposed that in primates, the time during S-phase when a gene is replicated is an important determinant of neutral rates of evolution. Here we ask 1) whether we can replicate this result in rodents, 2) whether different autosomes replicate on average at different times, and 3) whether this might explain differences in their substitution rates. Finally we ask 4) whether X, Y, and autosome replicate at different times and 5) whether any difference might explain why the number of replication events alone cannot explain their substitution rates. We find that, as in primates, autosomal intronic rates of evolution increase significantly during S-phase. Different autosomes do have different average replication times, and together with rearrangement, this is a significant predictor of between-autosome differences in substitution rate. Although we find that autosomal, X-, and Y-linked genes replicate at different times, it is paradoxical that the Y-linked genes replicate latest, and replicate more often, but are not especially fast evolving. These results support the hypothesis that replication timing is an important source of substitution rate heterogeneity.