Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data.
Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data.
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DOI：
10.1371/journal.pgen.1000695
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
Bustamante CD
中科院分区：
文献类型：
--
作者：
Gutenkunst RN;Hernandez RD;Williamson SH;Bustamante CD
根据遗传数据建立的人口统计模型在阐明史前事件和在基因组扫描中充当空模型以进行选择方面发挥了重要作用。我们介绍了一种基于种群内和种群间遗传变异的联合频谱的推断方法。对于候选模型，我们使用一个座位，两个等位基因的Wright-Fisher过程的扩散近似来数值计算期望谱，涉及多达三个同时的群体。我们的方法是复合似然方案，因为中性基因座之间的联系改变了频谱的方差，但不改变了预期。因此，我们使用包含关联的自助法来估计参数的不确定性和假设检验的有意义的值。我们的方法还可以结合单个位置的选择，预测所选等位基因在经历一系列进化力量的种群中的联合分布，包括扩张、收缩、迁移和混合。我们用环境基因组计划对来自4个种群(YRI、CHB、CEU和MXL)的68个个体的5Mb非编码DNA重新测序，模拟了人类从非洲扩张到新大陆的过程。我们推断出14万年前西非和欧亚人口之间的差异(95%可信区间：40-270 kya)。这比其他基因研究要早，部分原因是我们纳入了迁徙。我们估计欧洲(CEU)和东亚(CHB)的分化时间为23kya(95%C.I.：17-43kya)，这是在考古学证据将现代人类放在欧洲很久之后。最后，我们估计东亚人(CHB)和墨西哥裔美国人(MXL)之间的差异为22kya(95%C.I.：16.3-26.9kya)，我们的分析没有发现后续移民的证据。此外，将我们的人口统计学模型与先前估计的新出现的氨基酸突变之间的选择效应分布相结合，可以准确地预测三个大陆群体(YRI、CHB、CEU)的非同义变异的频谱。我们物种的人口历史反映在种群内部和种群之间的遗传变异模式上。我们开发了一种有效的方法来计算遗传变异的预期分布，给出了一个包括种群大小变化、种群分裂和连接以及迁移等事件的人口模型。我们将我们的方法应用于可公开获得的人类测序数据，寻找最能再现观察到的模式的模型。我们对非洲、欧洲和亚洲人口数据的联合分析得出了这些人口分化的新日期。特别是，我们发现非洲人和欧亚人在大约10万年前出现了分化。这比其他基因研究表明的要早，因为我们的模型包括了迁徙的影响，我们发现这对再现数据中观察到的变异模式很重要。我们还分析了来自欧洲、亚洲和墨西哥人口的数据，以模拟美洲的人口结构。在这里，我们没有发现东亚人和美洲原住民人口分化后反复迁徙的证据。我们的方法并不局限于研究人类，我们希望未来的测序项目将为我们自己和其他物种的历史提供更多的见解。
Demographic models built from genetic data play important roles in illuminating prehistorical events and serving as null models in genome scans for selection. We introduce an inference method based on the joint frequency spectrum of genetic variants within and between populations. For candidate models we numerically compute the expected spectrum using a diffusion approximation to the one-locus, two-allele Wright-Fisher process, involving up to three simultaneous populations. Our approach is a composite likelihood scheme, since linkage between neutral loci alters the variance but not the expectation of the frequency spectrum. We thus use bootstraps incorporating linkage to estimate uncertainties for parameters and significance values for hypothesis tests. Our method can also incorporate selection on single sites, predicting the joint distribution of selected alleles among populations experiencing a bevy of evolutionary forces, including expansions, contractions, migrations, and admixture. We model human expansion out of Africa and the settlement of the New World, using 5 Mb of noncoding DNA resequenced in 68 individuals from 4 populations (YRI, CHB, CEU, and MXL) by the Environmental Genome Project. We infer divergence between West African and Eurasian populations 140 thousand years ago (95% confidence interval: 40–270 kya). This is earlier than other genetic studies, in part because we incorporate migration. We estimate the European (CEU) and East Asian (CHB) divergence time to be 23 kya (95% c.i.: 17–43 kya), long after archeological evidence places modern humans in Europe. Finally, we estimate divergence between East Asians (CHB) and Mexican-Americans (MXL) of 22 kya (95% c.i.: 16.3–26.9 kya), and our analysis yields no evidence for subsequent migration. Furthermore, combining our demographic model with a previously estimated distribution of selective effects among newly arising amino acid mutations accurately predicts the frequency spectrum of nonsynonymous variants across three continental populations (YRI, CHB, CEU). The demographic history of our species is reflected in patterns of genetic variation within and among populations. We developed an efficient method for calculating the expected distribution of genetic variation, given a demographic model including such events as population size changes, population splits and joins, and migration. We applied our approach to publicly available human sequencing data, searching for models that best reproduce the observed patterns. Our joint analysis of data from African, European, and Asian populations yielded new dates for when these populations diverged. In particular, we found that African and Eurasian populations diverged around 100,000 years ago. This is earlier than other genetic studies suggest, because our model includes the effects of migration, which we found to be important for reproducing observed patterns of variation in the data. We also analyzed data from European, Asian, and Mexican populations to model the peopling of the Americas. Here, we find no evidence for recurrent migration after East Asian and Native American populations diverged. Our methods are not limited to studying humans, and we hope that future sequencing projects will offer more insights into the history of both our own species and others.
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影响因子：
9.8
作者：
Akey JM;Eberle MA;Rieder MJ;Carlson CS;Shriver MD;Nickerson DA;Kruglyak L
通讯作者：
Kruglyak L
影响因子：
2.8
作者：
Fenner, JN
通讯作者：
Fenner, JN
影响因子：
56.9
作者：
Hernandez, Ryan D.;Hubisz, Melissa J.;Bustamante, Carlos D.
通讯作者：
Bustamante, Carlos D.
DOI：
10.1073/pnas.0404142101
发表时间：
2004-09-28
影响因子：
11.1
作者：
Hwang, DG;Green, P
通讯作者：
Green, P
影响因子：
3.3
作者：
Adams, AM;Hudson, RR
通讯作者：
Hudson, RR