Y CHROMOSOME EVOLUTION AND MODERN HUMAN ORIGINS

Y染色体在人类进化研究中有着巨大的潜力。 由于其父系遗传方式和缺乏重组， Y染色体的男性特异性部分提供了最好的机会， 基于母系遗传的线粒体DNA测试假设。 的 该提案的总体目标是开发和使用Y染色体， 一个工具来测试假设1）的系统发育关系， 人类和类人猿，2）现代的起源和迁移模式 人类群体，3）和男性介导的基因流在选定的区域， 世界 这一建议描绘了第一个全面的努力，审查 基因组上的遗传学上有用的点突变和插入/缺失 人类Y染色体。一个数字的分布和频率 以前确定的Y特异性多态性将在一个 来自所有有人居住的大陆的2300人样本。 PCR突变 检测方法如单链构象多态性和 DNA异源双链分析，将用于检测新的Y连锁 多态性酶促错配切割，一种新技术， 与目前的突变检测方法相比有几个优点，并有望 对健康相关的研究有用，将被开发。快速方法， 将在大群体样本中确定基因型点突变， 设计的此外，至少五个Y特异性单拷贝DNA的双链酶， 将对16名人类和4种类人猿的DNA进行测序（潘 troglodytes，Pan paniscus，Gorilla gorilla和Pongo pygmaeus）。这些 经过综合努力，将对大约24个案例进行比较 每个Y染色体的独特DNA来自不同地理环境的人类， 背景除了这些点突变的比较， 插入/缺失，高变微卫星的潜在价值 评估遗传多样性水平、基因流动程度和 将调查种群间的亲缘关系。 这些数据将用于1）构建Y染色体单倍型，2）构建 使用类人猿作为外群的Y-单倍型系统发育树，3） 确定独特Y连锁序列的进化速率，4）估计 人类群体和不同Y染色体上的遗传多样性程度 单倍型，和5）确定人类之间的遗传关系 人口。当前的分支模型将被探索， 关于Y系年龄的信息，以及Y系的大小和地理位置， 祖先居住的地方。这可能有助于区分 当代Y染色体在H之前就开始多样化。直立人 人口从非洲扩散出去超过或等于100万年 或者更近一些，在现代人口的增长时期。 最后，这些数据将用于解决有关男性的假设- 在亚洲和欧洲介导的基因流，和在日本的混合物。这些 来自父亲的数据将补充不断增长的语言财富， 形态学和考古学数据，以及来自 常染色体和线粒体DNA研究。

The Y chromosome holds great promise for human evolutionary research. Because of its paternal mode of inheritance and lack of recombination, the male-specific portion of the Y chromosome provides the best opportunity to test hypotheses based on maternally-inherited mitochondrial DNA. The overall goals of this proposal are to develop and use the Y chromosome as a tool to test hypotheses regarding 1) the phylogenetic relationships of humans and great apes, 2) the origin and migration patterns of modern human populations, 3) and male-mediated gene flow in selected regions of the world. This proposal delineates the first comprehensive effort to examine phylogenetically useful point mutations and insertion/deletions on the human Y chromosome. The distribution and frequency of a number of previously ascertained Y-specific polymorphisms will be determined in a sample of 2300 humans from all inhabited continents. PCR-based mutation detection methods such as single-stranded conformation polymorphism and DNA heteroduplex analysis, will be used to detect new Y-linked polymorphisms. Enzymatic mismatch cleavage, a new technique that offers several advantages over current mutation detection methods and promises to be useful for health-related research, will be developed. Rapid methods to genotype confirmed point mutations in large population samples will be devised. Furthermore, at least five kilobases of Y-specific single-copy DNA will be sequenced from 16 humans and four species of great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, and Pongo pygmaeus). These combined efforts will result in comparisons of approximately 24 kilobases of unique DNA per Y chromosome from humans with diverse geographical backgrounds. In addition to these comparisons of point mutations and insertion/deletions, the potential value of hypervariable microsatellite markers in assessing levels of genetic diversity, extent of gene flow and affinities among populations will be investigated. The data will be used to 1) construct Y chromosome haplotypes, 2) build phylogenetic trees of Y-haplotypes using great apes as an outgroup, 3) determine evolutionary rates of unique Y-linked sequences, 4) estimate the degree of genetic diversity in human populations and on different Y- haplotypes, and 5) determine genetic relationships among human populations. Current cladistic models will be explored t derive information about the age of Y-lineages, and the size and geographical locations of ancestral populations. This may help to distinguish whether contemporary Y chromosomes began diversifying before H. erectus populations spread out of Africa more than or equal to 1 million years ago, or more recently, during the rise of modern human populations. Finally, the data will be used to address hypotheses concerning male- mediated gene flow in Asia and Europe, and admixture in Japan. These paternally-derived data will complement the growing wealth of linguistic, morphological and archaeological data, as well as data derived from autosomal and mitochondrial DNA studies.