Live hot, die young: Transmission distortion in recombination hotspots
Live hot, die young: Transmission distortion in recombination hotspots
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DOI：
10.1371/journal.pgen.0030035
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发表时间：
2007-03-01
期刊：
影响因子：
4.5
通讯作者：
Myers, Simon R.
中科院分区：
文献类型：
--
作者：
Coop, Graham;Myers, Simon R.
有强有力的证据表明，人类减数分裂重组的热点是基因组的瞬时特征。例如，人类和黑猩猩之间不共享热点位置。偏向于局部干扰热点的等位基因的基因转换可能是热点寿命短的一个解释。我们调查了这种偏见对人类热点及其演变的影响。我们的结果表明，基因转换偏见是一个足够强大的力量，足以产生观察到的物种之间缺乏强烈热点共享的现象，尽管共享可能在较弱的热点中更为常见。我们调查了热点如何产生的模型，并发现只有热点等位基因最初没有经历驱动的模型才与对人类基因组中相当热点的观察一致。与DRIVE相反的突变不能成功地将这样的热点引入种群，即使有直接选择以获得更高的重组率，例如确保减数分裂期间的正确分离。我们探索了热点等位基因对单倍型变异模式的影响，并表明这些等位基因掩盖了它们在群体遗传数据中的存在，使得它们很难被检测到。
There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect.