Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes
Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes
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DOI：
10.1371/journal.pgen.1005550
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发表时间：
2015-11-01
期刊：
影响因子：
4.5
通讯作者：
Reich, David
中科院分区：
文献类型：
--
作者：
Lipson, Mark;Loh, Po-Ru;Reich, David
人类的突变率是研究我们物种进化、解释当今遗传变异和了解遗传病发病率的重要参数。然而，我们目前对这一比率的估计是不确定的。最值得注意的是，最近基于家系中新基因突变计数的方法比基于序列差异的经典方法产生的值要小得多。在这里，我们提出了一种新的方法，使用精细的人类重组图来校准突变累积的速度。通过将二倍体基因组中的局部杂合度水平与这些水平变化的遗传距离尺度进行比较，我们能够估计出平均在数百或数千代之间的长期突变率。我们推断每代每个碱基有1.61+/-0.13 x 10(-8)突变的比率，这介于系统发育和基于系谱的估计之间，我们建议了可能的机制来使我们的估计与以前的研究相一致。我们的结果支持人类种群之间以及人类与其他类人猿之间的中年分化。
The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 +/- 0.13 x 10(-8) mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.