The Population Genetics of Divergence

种群分化，包括物种形成和种群结构的起源， 进化过程导致生命的多样性。该研究项目将扩展最近的进展， 基于似然性的发散模型方法。新的方法采用了分析集成比前 马尔可夫链蒙特卡罗框架内的模型参数的分布。该方法导致一种接头， 概率密度函数，与可能性成比例，可用于参数估计和对数， 嵌套人口模型的似然比检验。 新方法适用于一般的多种群发散问题。此类问题 长期以来一直被认为需要种群遗传学观点和系统发育观点。的 研究计划概述了如何将这两者结合在一个共同的MCMC模拟下。这将 是第一个这样的方法，不假设一个给定的遗传;这并不假设基因流没有 发生;这并没有假设抽样或祖先的相对人口规模 人口。通过提供与可能性成比例的联合后验密度的估计，该方法 将提供对对数似然比检验和基于似然的置信区间的直接访问。 该方法还将扩展到样本识别和DNA条形码方面的问题。 这些新的方法将应用于一个物种和亚种之间的分歧的案例研究， 黑猩猩该方法也将被应用于大型多群体多位点数据集，从人类 人口。 履约地点（组织、城市、州） 美国新泽西新玩法罗格斯大学州立大学 哥本哈根大学，哥本哈根，丹麦。 PHS 398（04/06修订版）第2页表格第2页 首席研究员/项目主任（最后，第一，中间）：嘿，伊曼纽尔B。 关键人员。参见说明。根据需要使用续页，以下列格式提供所需信息。 从主要研究者开始。按字母顺序列出所有其他关键人员，姓在前。 名称eRA Commons用户名组织在项目中的角色 嘿，伊曼纽尔B。EMANUELHEY罗格斯大学PI Nielsen，Rasmus哥本哈根大学 其他重要贡献者 名称组织在项目中的角色 人胚胎干细胞[x]否Q是 如果拟开展的项目涉及人类胚胎干细胞，请在下面列出以下列表中特定细胞系的注册号： http://stemcells.nih.qov/reqistrv/index.asp.根据需要使用续页。 如果此时无法引用特定行，请说明将使用注册表中的一条。 细胞系 PHS 398（04/06修订版）第3页表格第2页-续 将下列各页依次编号 应用程序.不要使用后缀，如4a，4 b。 首席研究员/项目主管（最后一个，第一个，中间一个）：嘿，伊曼纽尔B 主要研究者/项目负责人的姓名必须在打印页和续页的顶部提供。 研究资助 目录 页码 首页1 描述、绩效研究中心、关键人员、其他重要贡献者和人类 胚胎干细胞 目录 初始预算期间的详细预算（或模块预算） 整个拟议支助期的预算（不适用于模块预算）na 与联营体/合同安排有关的预算（不适用于模块预算） 简历-主要研究者/项目负责人（不超过四页） 其他个人简介（每份不超过四页-见说明） 资源12 研究计划，13 重新提交/重新提交申请的简介（不超过3页）。13 补充/修订申请简介（不超过一页。）na A.具体目标Jl B。背景与意义17 C.初步研究/进度报告（项目A-D：不超过25页）。22 D.研究设计与方法34 E.人类研究41 人类受试者保护（如果正面页面上的第4项标记为“是”，则需要）na 数据和安全性监测计划（如果正面页面上的第4项标记为“是”，则需要， 或III期临床试验）na 纳入女性和少数民族（如果正面页面上的项目4标记为“是”且为临床研究，则需要）na 目标/计划入组表（针对新的和正在进行的临床研究） 包括儿童（如果正面页面上的第4项标记为“是”，则需要）na F.脊椎动物 G.选择代理研究名称 H.引用文献41 I，多个PI领导计划46 J.联营集团/合同安排 K.资源共享名称 L.支持信（例如，顾问） 清单。47 检查是否 附录（五套，不需要额外包装） 阑尾是 包括 接受出版的出版物和手稿数量（不超过10份） 其他项目（列表）： PHS 398（04/06修订版）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. Human Subjects Research 41 Protection of Human Subjects (Required if Item 4 on the Face Page is marked "Yes") na Data and Safety Monitoring Plan (Required if Item 4 on the Face Page is marked "Yes" and a Phase I, II, or III clinical trial is proposed) na Inclusion of Women and Minorities (Required if Item 4 on the Face Page is marked "Yes" and is Clinical Research) na Targeted/Planned Enrollment Table (for new and continuing clinical research studies) na Inclusion of Children (Required if Item 4 on the Face Page is marked "Yes") na F. Vertebrate Animals na G. Select Agent Research na H. Literature Cited 41 I, Multiple PI Leadership Plan 46 J. Consortium/Contractual Arrangements 46 K. Resource Sharing na L. Letters of Support (e.g., Consultants) na Checklist. 47 Check if Appendix(Fivecollatedsets.NopagenumberingnecessaryforAppendix.) 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