Y CHROMOSOME EVOLUTION AND MODERN HUMAN ORIGINS

Y染色体为人类进化研究带来了巨大的希望。 由于它的父系遗传模式和缺乏重组， Y染色体的男性特有部分提供了最好的机会 测试基于母系遗传的线粒体DNA的假设。这个 这项提案的总体目标是开发和使用Y染色体作为 一种工具，用来检验关于1)系统发育关系的假设 人类和类人猿，2)现代人类的起源和迁徙模式 人类种群，3)和男性介导的基因流动在选定的区域 整个世界。 这项提案勾勒出了审查的第一个全面努力 在系统发育上有用的点突变和插入/缺失 人类Y染色体。一些物种的分布和频率 之前确定的Y基因特定的多态将在 来自所有有人居住的大陆的2300名人类的样本。基于PCR的突变 检测方法如单链构象多态和 DNA异源双链分析，将用于检测新的Y连锁 多态现象。酶错配切割，一种新的技术，提供了 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的，将被开发。快速方法来实现 在大量人群样本中确认的基因突变将是 精心设计的。此外，至少5千个碱基的Y特定的单拷贝 DNA将从16个人类和4个物种的类人猿(潘 猩猩、黑猩猩、大猩猩和Pongo Pigmaeus)。这些 综合努力将产生大约24千个碱基的比较 来自不同地理位置的人每条Y染色体的独特DNA 背景。除了这些点突变和 插入/缺失，高变量微卫星的潜在价值 评估遗传多样性水平、基因流动程度和 将调查人群之间的亲和力。 这些数据将被用来1)构建Y染色体单倍型，2)构建 以类人猿为外群的Y单倍型系统发育树，3) 确定唯一Y连锁序列的进化速率，4)估计 不同Y-Y基因在人类群体中的遗传多样性程度 单倍型，以及5)决定人类之间的遗传关系 人口。当前的分支模型将被探索以派生 关于Y世系的年龄、大小和地理位置的信息 祖先种群的位置。这可能有助于区分 当代Y染色体在直立人之前就开始多样化 从非洲传出的人口超过或等于100万年 在现代人的崛起之前，或者更近的时候。 最后，这些数据将被用来解决关于男性-- 在亚洲和欧洲中介基因流动，在日本混杂。这些 家长派生的数据将补充日益增长的语言财富， 形态和考古数据，以及源自 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.