Collaborative Research: A Novel Genetic Database to Test Models of Human Origins

人类基因组掌握着人类起源之谜的线索。随着最近人类基因组序列初稿的完成，科学家们现在能够检查多个人类群体中整个基因组的变异模式。这样的承诺将有助于理解数万年前发生的事件，并更好地设计研究，以绘制与当今人类疾病有关的基因图谱。在这个项目中，来自遗传学不同领域(包括理论和经验种群遗传学)的科学家将收集新的数据并设计新的分析方法来回答人类进化中长期存在的问题。这项研究的一个重点是“古老的”人类群体(如欧洲的尼安德特人和亚洲的直立人)与现代人的进化关系。古代人对当代人类基因库有没有贡献，或者尼安德特人和直立人在过去10万年内扩张出非洲时，是否被现代人完全取代(没有杂交)？今天群体的祖先是在非洲一小块与世隔绝的地区向现代形式过渡，还是在更广泛的地理范围内利用不同种群的基因贡献向现代形式过渡？这项研究的另一个重点是人口增长。虽然我们目前的人口规模超过60亿，但长期平均人口规模可能远远低于100万。人类人口是什么时候开始急剧扩张的？这种增长是否与人类历史上的某个特定事件有关，比如语言的出现或农业的发明？这个合作项目试图通过建立一个当代人类DNA序列的公共数据库，并开发分析数据所需的计算工具，来解决这些问题和相关问题。DNA序列将从6个地理上不同的种群的代表的基因组的90个区域中提取(例如，3个来自撒哈拉以南非洲，3个来自欧亚大陆)，以及人类最接近的近亲--大猩猩。将开发统计和计算方法，以严格检验替代假设的预测。这一项目的成果将通过一个公共网站和将在第四年组织的关于人类起源的跨学科专题讨论会向更多的受众传播。这项研究有几个更广泛的影响。首先，它将鼓励来自遗传学、古生物学、考古学和历史语言学的研究人员之间的辩论和互动。其次，研究将整合研究、教学和社区推广。本科生、研究生和博士后将接受理论技能和实验技能相结合的培训。亚利桑那大学和南加州大学都有从代表不足的少数族裔中寻找有前途的候选人的项目，这些学生将被招募参与该项目。在培养新一代人类学遗传学家的同时，该项目将促进人类起源研究中的新发现。

The human genome holds clues to the mystery of human origins. With the recent completion of the first draft of the human genome sequence scientists are now in a position to examine patterns of variation across the entire genome in multiple human populations. Such an undertaking will facilitate an understanding of events that took place tens of thousands of years ago, and the better design of studies to map genes involved in human disease today. In this project, scientists from different fields within genetics (both theoretical and empirical population genetics) will gather new data and design novel analytical methods to answer long-standing questions in human evolution. One focus of this research is on the evolutionary relationships of "archaic" human groups (such as the Neanderthals in Europe and Homo erectus in Asia) to modern humans. Did archaic forms make any contribution to the contemporary human gene pool, or were Neanderthals and H. erectus completely replaced (without interbreeding) by modern humans as they expanded out of Africa within the last 100 thousand years? Did the ancestors of present day groups make the transition to modern form in a small, isolated part of Africa, or over a broader geographic range with genetic contributions from divergent populations. Another focus of this research is on human population growth. Although our current population size is more than 6 billion, the long-term average population size was probably substantially less than 1 million. When did human populations begin to expand dramatically in size? Was this growth associated with a particular event in human history, such as the advent of language or the invention of agriculture?This collaborative project seeks to address these and related topics by building a public database of DNA sequences from contemporary human populations, and by developing the computational tools necessary for the analysis of the data. DNA sequences will be otabined from 90 regions of the genome in representatives of six geographically diverse populations (e.g., three from sub-Saharan Africa and three from Eurasia), as well as representatives of humans closest living relatives, the great apes. Statistical and computational methods will be developed for rigorously testing the predictions of alternative hypotheses. The results of this project will be disseminated to a larger audience both through a public website and through an interdisciplinary symposium on human origins that will be organized in the fourth year. This research has several broader impacts. First, it will encourage debate and interaction among researchers from genetics, paleontology, archaeology, and historical linguistics. Second, the research will integrate research, teaching, and community outreach. Undergraduate students, graduate students, and post-doctoral fellows will be trained in a combination of theoretical and experimental skills. Programs are in place at both the University of Arizona and the University of Southern California for identifying promising candidates from underrepresented minorities and these students will be recruited to participate in the project. While training a new generation of anthropological geneticists this project will facilitate novel discoveries in human origins research.