Variation in heterozygosity predicts variation in human substitution rates between populations, individuals and genomic regions.
Variation in heterozygosity predicts variation in human substitution rates between populations, individuals and genomic regions.
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DOI：
10.1371/journal.pone.0063048
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Amos W
中科院分区：
文献类型：
--
作者：
Amos W
“杂合子不稳定性”（HI）假说表明，在减数分裂过程中集中在杂合位点的基因转换事件局部增加了突变率，但这一假说在很大程度上仍未得到验证。当人类离开非洲时，他们失去了变异性，如果HI起作用，应该会降低非非洲人的突变率。使用来自1，000个基因组计划的对齐的全基因组序列，在不同的人类中量化相对取代率。非洲人的替换率始终高于非非洲人，但仅在基因组的二倍体区域，与杂合性的作用一致。分析划分为一系列不重叠的2 Mb窗口的相同数据，揭示了“非洲以外”的杂合性丢失量与非洲人和非非洲人之间替代率差异之间存在强烈的非线性相关性。推定的最近的突变，衍生的变体，发生在80个人类染色体采样中只一次，优先发生在中心的2 Kb窗口，具有升高的杂合性相比，同一地区的密切相关的人口和同一人口中的紧邻区域。超过一半的替换似乎可归因于杂合性的变化。这一观察结果为HI提供了强有力的支持，并对进化生物学的许多分支产生了影响。
The “heterozygote instability” (HI) hypothesis suggests that gene conversion events focused on heterozygous sites during meiosis locally increase the mutation rate, but this hypothesis remains largely untested. As humans left Africa they lost variability, which, if HI operates, should have reduced the mutation rate in non-Africans. Relative substitution rates were quantified in diverse humans using aligned whole genome sequences from the 1,000 genomes project. Substitution rate is consistently greater in Africans than in non-Africans, but only in diploid regions of the genome, consistent with a role for heterozygosity. Analysing the same data partitioned into a series of non-overlapping 2 Mb windows reveals a strong, non-linear correlation between the amount of heterozygosity lost “out of Africa” and the difference in substitution rate between Africans and non-Africans. Putative recent mutations, derived variants that occur only once among the 80 human chromosomes sampled, occur preferentially at the centre of 2 Kb windows that have elevated heterozygosity compared both with the same region in a closely related population and with an immediately adjacent region in the same population. More than half of all substitutions appear attributable to variation in heterozygosity. This observation provides strong support for HI with implications for many branches of evolutionary biology.
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影响因子：
2.9
作者：
Amos W;Flint J;Xu X
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1007/bf02173638
发表时间：
1996-07-19
期刊：
MOLECULAR & GENERAL GENETICS
影响因子：
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作者：
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通讯作者：
Ninio, J