The Population Genetics of Divergence

提出的研究将解决现代人类遗传学的一个巨大挑战，即理解最近的 我们物种的进化史。这不仅作为关键的基础知识很重要，而且对许多医学遗传学来说也很重要 问题，如何时何地发生了导致疾病的突变。医疗行业的背景 这样的问题是人类人口的历史，其中包括我们的人口规模历史， 人口创建事件、迁徙和混杂以及人口规模变化。 将开发两种新的方法来估计物种的人口历史。这两个都是 旨在解决限制当前方法的三大挑战。首先，旨在研究 基因交换的历史必须包括重组作为模型的一部分，因为强烈的相互作用影响 重组和基因交换改变了遗传变异的模式。其次，方法必须能够处理大型、 人类人口的复杂人口模型。对于基因交换的历史来说，情况尤其如此。第三, 方法必须能够快速处理非常大的数据集，并且不会引入偏差。 一种新的方法将提供连接的单核苷酸对的等位基因频谱(AFS)的估计。 多态(SNPs)。通过包括SNP对的重组，2个SNP AFS要大得多，持有的数量也更多 在基因交换方面的信息比传统的基于单一SNP的AFS更多。 第二种新方法将是一种新的家谱抽样方法，它使用大大减少的 家谱(基因树)。这种方法不会泄露任何信息，但与大多数当前的家谱不同 采样器将能够用于重组模型和大型数据集。 第三个目标是将这些方法应用于研究非洲人口中的人类人口史。非洲 人口具有古老而复杂的遗传史，其中包括所考虑的所有主要人口统计过程 这里。这两种方法都将应用于一个大型的高质量人口基因组数据集，目前包括33个 7个种群的基因组，包括3个狩猎采集种群。我们的目标是建立一个准确而丰富的多元 非洲人类历史的人口肖像。

The propose research will address a great challenge of modern human genetics which is to understand the recent evolutionary history of our species. This is important not only as key basic knowledge, but also for many medical genetic questions, such as when and where have mutations occurred that contribute to diseases. The backdrop for medical questions like these is the demographic history of human populations, which includes our history of population sizes, population founding events, migrations and admixture, and population size changes. Two new methods for estimating the demographic history of a species will be developed. Both of these have been designed to address three major challenges that limit current methods. First, methods that are intended to study the history of gene exchange must include recombination as part of the model because of the strong interaction affect that recombination and gene exchange have on patterns of genetic variation. Second, methods must be able to handle large, complex demographic models with human populations. This is especially true for histories with gene exchange. Third, methods must be able to handle very large data sets with speed and without introducing biases. One new method will provide estimates of the Allele Frequency Spectrum (AFS) for pairs of linked single-nucleotide- polymorphisms (SNPs). By including recombination for pairs of SNPs, the 2 SNP AFS is far larger and holds much more information on gene exchange than the conventional single SNP-based AFS. The second new method will be a new genealogy sampling approach that uses a greatly reduced representation of genealogies (gene trees). This method does not give up any information, and yet unlike most current genealogy samplers will be able to be used for models with recombination and for large data sets. The third goal is to apply these methods to the study of human demographic history among African populations. African populations have ancient and complex genetic histories that include all of the major demographic processes considered here. Both methods will be applied to a large high-quality population genomic data set that currently includes 33 genomes from 7 populations, including three hunter-gatherer populations. The goal is an accurate and rich multi- population portrait of human history in Africa.