The Population Genetics of Divergence

种群分化，包括物种形成和种群结构的起源，是根本 进化过程导致了生命的多样性。这项研究项目将扩展最近的进展 基于可能性的发散模型方法。新方法采用分析集成，而不是先验的 马尔可夫链蒙特卡罗框架内模型参数的分布。该方法导致了一个关节 概率密度函数，与似然成正比，可用于参数估计和对数计算。 嵌套人口统计模型的似然比检验。 新方法将适用于发散中的一般多种群问题。这样的问题已经 长期以来，人们一直认为既需要种群遗传学的观点，也需要系统发育的观点。这个 研究计划概述了如何在通用的MCMC模拟下将这两者结合在一起。这将是 这是第一个不假设某一特定的系统发展史的方法；这并不是假设基因流动没有 这并没有对被采样或祖先的相对种群规模做出任何假设 人口。通过提供与似然成比例的联合后验密度的估计，该方法 将提供对数似然比检验和基于似然的置信度区间的直接访问。 该方法还将扩展到样本识别和DNA条形码的问题。 这些新的方法将被应用于一个案例研究物种和亚种之间的差异。 黑猩猩。该方法也将应用于来自人类的大型多种群多位点数据集 人口。 演出现场(S)(组织、市、州) 罗格斯大学，新泽西州立大学，新不伦瑞克，美国新泽西州 哥本哈根大学，哥本哈根，丹麦。 小灵通398(04/06版)第2页表格第2页 首席调查员/项目主任(最后、第一、中间)：嗨，伊曼纽尔·B。 关键人员。请参阅说明。根据需要使用续页，以如下所示的格式提供所需信息。 从首席调查员(S)开始。按字母顺序列出所有其他关键人员，姓氏在前。 名称时代共享用户名项目上的组织角色 嗨，伊曼纽尔·B·埃曼纽尔·罗格斯大学派 拉斯姆斯大学尼尔森分校。哥本哈根联合投资公司的 其他重要贡献者 命名项目中的组织角色 人类胚胎干细胞[x]否Q是 如果建议的项目涉及人类胚胎干细胞，请从下面的列表中列出特定细胞系(S)的注册号： Http://stemcells.nih.qov/reqistrv/index.asp.根据需要使用续页。 如果指定线路注释，请参考这次的日期，includeastatementthatonefromtheRegistrywillbeused. 细胞系 小灵通398(04/06版)第3页表格第2页-续 从头到尾连续地给下面的页面编号 应用程序。不要使用诸如4a、4b之类的后缀。 首席研究员/项目主任(最后、第一、中间)：嗨，伊曼纽尔·B 必须在每张打印页和每张续页的顶部提供首席调查员/项目主任的姓名。 研究补助金 目录 页码 正面第1页 描述、绩效地点、关键人员、其他重要贡献者和人员 胚胎干细胞 目录表 初始预算期间的明细预算(或模块预算) 整个建议支持期限的预算(不适用于模块预算)NA 与联合体/合同安排有关的预算(不适用于模块预算)NA 个人简介-首席调查员/项目主任(不超过四页) 其他传记小品(每份不超过四页-见说明书) 资源12 研究计划，13 审核/重新提交申请简介(不超过3页)。13 补充/修订申请简介(不超过一页)北美 A.具体目标JL B.背景和意义17 C.初步研究/进度报告(项目A-D：不超过25页)。22 D.研究设计和方法34 E.人类受试者研究41 保护人类受试者(如正面第4项标记为“是”，则为必填项)NA 数据和安全监控计划(如果页面上的第4项被标记为是并且阶段I、II、 或建议进行III临床试验)NA 纳入妇女和少数群体(如果脸页上的第4项标记为“是”并且是临床研究，则需要)NA 目标/计划注册表(用于新的和继续的临床研究)北美 包括儿童(如果主页上的第4项标记为“是”，则为必填项) F.脊椎动物NA G.选择代理研究NA H.文献引文41 I，多重PI领导计划46 J.联合体/合同安排46 K.资源共享NA L.支持函(例如，顾问)NA 核对表。47 检查是否 Appendix(Fivecollatedsets.NopagenumberingnecessaryforAppendix.) 附录为 包括在内 接受出版的出版物和稿件数量(不超过10份) 其他项目(列表)： 小灵通398(04/06版)第4页表格第3页

Population divergence, including speciation and the origins of population structure, is the fundamental evolutionary process leading to the diversity of life. This research project will extend recent advances in a likelihood-based approach to divergence models. The new approach employs analytic integration over prior ditributions of model parameters within a Markov chain Monte Carlo framework. The method leads to a joint probability density function, proportional to the likelihood, that can be used for parameter estimation and log- likelihood ratio tests of nested demographic models. The new method will be adapted to general multi-population problems in divergence. Such problems have long been appreciated as requiring both a population genetic perspective and a phylogenetic perspective. The research plan outlines how these two can be brought together under a common MCMC simulation. This will be the first such method that does not assume a given phylogeny; that does not assume that gene flow has not occurred; and that makes no assumptions about the relative population sizes of sampled or ancestral populations. By providing estimates of the joint posterior density, proportional to the likelihood, the method will provide direct acces to log-likelihood ratio tests and to likelihood-based confidence intervals. The approach will also be extended to problems in sample identification and DNA barcoding. These new methods will be applied to a case study of divergence among species and subspecies of Chimpanzee. The methods will also be applied to large multi-population multi-locus data sets from human populations. PERFORMANCE SITE(S) (organization, city, state) Rutgers, the State University of New Jersy, New Brunswick New Jersey, USA The University of Copenhagen, Copenhagen, Denmark. PHS 398 (Rev. 04/06) Page 2 Form Page 2 Principal Investigator/Program Director (Last, First, Middle): Hey, Emanuel B. KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator(s). List all other key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project Hey, Emanuel B. EMANUELHEY Rutgers University PI Nielsen, Rasmus Univ. of Copenhagen Co-Pi OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Human Embryonic Stem Cells [x] No Q yes If the proposed project Involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following list: http://stemcells.nih.qov/reqistrv/index.asp. Use continuation pages as needed. Ifaspecificlinecannotbereferencedatthistime,includeastatementthatonefromtheRegistrywillbeused. Cell Line PHS 398 (Rev. 04/06) Page 3 Form Page 2-continued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. Principal Investigator/Program Director (Last, First, Middle): Hey, Emanuel B The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, Performance Sites, Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells Table of Contents Detailed Budget for Initial Budget Period (or Modular Budget) Budget for Entire Proposed Period of Support (not applicable with Modular Budget) na Budgets Pertaining to Consortium/Contractual Arrangements (not applicable with Modular Budget) na Biographical Sketch - Principal Investigator/Program Director (Not to exceed four pages) Other Biographical Sketches (Not to exceed four pages for each - Seeinstructions) Resources 12 Research Plan, 13 Introduction to Revlsed/Resubmission Application (Not to exceed 3 pages.). 13 Introduction to Supplemental/Revision Application (Not to exceed one page.) na A. Specific Aims Jl B. Background and Significance 17 C. Preliminary Studies/Progress Report (Items A-D: not to exceed 25 pages). 22 D. Research Design and Methods 34 E. 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Appendix is Included Number of publications and manuscripts accepted for publication (not to exceed 10) Other items (list): PHS 398 (Rev. 04/06) Page 4 Form Page 3