Explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa
Explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa
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DOI：
10.1073/pnas.0903341106
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发表时间：
2009-09-22
影响因子：
11.1
通讯作者：
Rosenberg, Noah A.
中科院分区：
文献类型：
--
作者：
DeGiorgio, Michael;Jakobsson, Mattias;Rosenberg, Noah A.
对世界范围内人类变异的研究发现，随着与东非地理距离的增加，汇总统计数据显示出三种趋势：杂合性降低，连锁不平衡（LD）增加，祖先等位基因频谱斜率降低。非连锁基因座的正向模拟表明，杂合度的下降可以用一个序列奠基人模型来描述，在这个模型中，种群从非洲向外迁移的过程中，每一个系列种群都是在向外扩张的过程中由前一个种群的一个子集形成的。在这里，我们通过开发一个包含链接基因座的基于聚结的回顾性序列创始人模型来扩展这种方法。我们的模型既恢复了观察到的杂合度随着与非洲距离的增加而下降的现象，也产生了在LD和祖先等位基因频谱中观察到的模式。令人惊讶的是，尽管在继续解释这三种趋势的同时，该模型可以容纳邻近种群之间的迁移以及现代和古人类之间有限的混合，但另一个竞争性模型——现代人类向外迁移的浪潮扩展到一系列先前存在的古人类——产生的模式与数据中观察到的几乎相反。最后，我们开发了一个更简单的模型来说明，允许序列创始人模型而不是古老的持久性模型来解释随着与非洲距离的增加而观察到的三种趋势的特征是，它结合了人类殖民世界时遗传漂变的累积效应。
Studies of worldwide human variation have discovered three trends in summary statistics as a function of increasing geographic distance from East Africa: a decrease in heterozygosity, an increase in linkage disequilibrium (LD), and a decrease in the slope of the ancestral allele frequency spectrum. Forward simulations of unlinked loci have shown that the decline in heterozygosity can be described by a serial founder model, in which populations migrate outward from Africa through a process where each of a series of populations is formed from a subset of the previous population in the outward expansion. Here, we extend this approach by developing a retrospective coalescent-based serial founder model that incorporates linked loci. Our model both recovers the observed decline in heterozygosity with increasing distance from Africa and produces the patterns observed in LD and the ancestral allele frequency spectrum. Surprisingly, although migration between neighboring populations and limited admixture between modern and archaic humans can be accommodated in the model while continuing to explain the three trends, a competing model in which a wave of outward modern human migration expands into a series of preexisting archaic populations produces nearly opposite patterns to those observed in the data. We conclude by developing a simpler model to illustrate that the feature that permits the serial founder model but not the archaic persistence model to explain the three trends observed with increasing distance from Africa is its incorporation of a cumulative effect of genetic drift as humans colonized the world.