The X Chromosome and Human Origins

这项研究的主要目的是利用X染色体上经历低到高重组量的四个基因的DNA序列变异模式来研究现代人类的起源。 在过去的十年中，线粒体，Y染色体和常染色体基因的研究已被用来推断长期有效的人口规模，年龄的血统，祖先血统的位置，模式和主要迁移的时间，人口扩张，混合物，瓶颈，以及不同种族群体的遗传亲和力。然而，最近的分子群体遗传学研究表明，基因组中的许多基因受到连锁位点选择的影响，因此不能作为跟踪群体过程的有用标记。基因组中重组率最高的区域的基因可能是评估人类起源模型中几个重要参数的最佳候选者，包括聚结时间和有效人口大小。拟议的研究将明确评估从最近非洲替代模型到多区域进化模型的连续模型，使用X染色体的数据。 特别是，这项研究将（1）准确估计到最近的共同祖先的时间和单个地理区域和整个人类物种的有效人口规模，（2）根据遗传变异模式重建不同地理群体的关系，和（3）提供了对自然选择作用于降低经历低重组率的基因组区域的遗传变异性的假设的进一步检验。 将通过对全球40例人类和类人猿（黑猩猩和矮猩猩）代表样本中的两个高重组基因和两个低重组基因中的每一个的非编码DNA进行测序来分析变异。 对于这两个低重组基因，将使用突变检测方法（DHPLC）和DNA测序对代表许多主要种族群体的另外350名个体进行调查。 X染色体变异的全球调查将为检验解剖学上现代人类种群的起源及其随后在世界各地的扩散提供一个关键框架。 在这项研究中产生的数据也将提供一个最详细的图片的遗传变异的结构在核苷酸水平上在一个大的世界范围内的样本，并将有助于确定不同的力量（突变，漂移，选择和重组）的相对重要性，在塑造模式的DNA序列变异在我们的物种。

The primary objective of the proposed research is to study the origin of modern humans using patterns of DNA sequence variation at four genes experiencing low to high amounts of recombination on the X chromosome. Within the last ten years, studies of mitochondrial, Y chromosome, and autosomal genes have been used to make inferences about long-term effective population size, age of lineages, location of ancestral lineages, pattern and timing of major migrations, population expansions, admixtures, and bottlenecks, and the genetic affinities of different ethnic groups. However, recent studies in molecular population genetics have revealed that many genes in the genome are influenced by selection at linked sites and thus do not serve as useful markers for tracking population processes. Genes in regions of the genome experiencing the highest rates of recombination are likely to be the best candidates for evaluating several important parameters of interest in models of human origins, including coalescence time and effective population size.The proposed research will explicitly evaluate a continuum of models from the Recent African Replacement model to the Multiregional Evolution model using data from the X chromosome. In particular, this research will (1) accurately estimate the time to the most recent common ancestor and the effective population size for individual geographic regions and for the human species as a whole, (2) reconstruct relationships of different geographic groups from patterns of genetic variation, and (3) provide a further test of the hypothesis that natural selection is acting to reduce genetic variability in genomic regions experiencing low rates of recombination. Variation will be assayed by sequencing non-coding DNA in each of two high-recombination genes and two low-recombination genes in a global sample of 40 humans and representatives of the great apes (Pan troglodytes and Pongo pygmaeus). For the two low-recombination genes, an additional 350 individuals representing many major ethnic groups will be surveyed using a mutation detection method (DHPLC) and DNA sequencing.This proposal represents a collaborative effort that combines expertise in human evolution and population genetics. Global surveys of X chromosome variation will provide a critical framework for testing hypotheses on the origins of anatomically modern human populations and their subsequent dispersals throughout the world. The data generated in this research will also provide one of the most detailed pictures of thestructure of genetic variation at the nucleotide level in a large worldwide sample and will help determine the relative importance of different forces (mutation, drift, selection, and recombination) in shaping patterns of DNA sequence variation in our species.