The Population Genetics of Divergence

分歧的群体遗传学

• 批准号: 8698900
• 负责人: Emanuel Hey
• 金额: $ 23.34万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698900
• 关键词: Address; Americas; Budgets; Case Study; Cell Line; Child; Chromosome Mapping; Cities; Clinical Research; Clinical Trials; Complex; Confidence Intervals; DNA; Data; Data Set; Denmark; Development; Enrollment; Event; Evolution; Face; Genealogy; General Population; Genes; Genetic; Genetic Drift; Human; Human Resources; Human Subject Research; Individual; Instruction; Joints; Last Name; Leadership; Letters; Life; Linkage Disequilibrium; Literature; Manuscripts; Markov Chains; Methods; Minority; Modeling; Monitor; Monte Carlo Method; Names; New Brunswick; New Jersey; Pan Genus; Pattern; Phase; Phylogenetic Analysis; Phylogeny; Population; Population Genetics; Population Group; Population Sizes; Principal Investigator; Printing; Probability; Process; Progress Reports; Protocols documentation; Publications; Publishing; Recording of previous events; Relative (related person); Research; Research Design; Research Methodology; Research Personnel; Research Project Grants; Resource Sharing; Resources; Role; Safety; Sampling; Space Simulation; Structure; Testing; Trees; Uncertainty; Universities; Update; Vertebrates; Woman; base; density; human embryonic stem cell; human subject protection; improved; indexing; joint function; novel strategies; performance site; programs; research study; simulation; tool

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

种群分化，包括物种形成和种群结构的起源，是根本性的 进化过程导致生命的多样性。该研究项目将扩展以下领域的最新进展 基于可能性的分歧模型方法。与之前的方法相比，新方法采用了分析集成 马尔可夫链蒙特卡罗框架内模型参数的分布。该方法导致联合 概率密度函数，与可能性成正比，可用于参数估计和对数 嵌套人口统计模型的似然比检验。 新方法将适用于分歧中的一般多群体问题。此类问题有 长期以来，人们认为需要群体遗传学视角和系统发育视角。这 研究计划概述了如何将这两者结合到一个共同的 MCMC 模拟中。这将 是第一个不假设给定系统发育的此类方法；这并不假设基因流动没有 发生；并且没有假设样本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。 该方法还将扩展到解决样本识别和 DNA 条形码问题。 这些新方法将应用于物种和亚种之间差异的案例研究 黑猩猩。该方法还将应用于来自人类的大型多群体多位点数据集 人口。 绩效站点（组织、城市、州） 罗格斯大学，新泽西州立大学，美国新泽西州新不伦瑞克 哥本哈根大学，丹麦哥本哈根。 PHS 398（修订版 04/06）第 2 页 表格第 2 页 首席研究员/项目总监（最后、第一、中间）：嘿，Emanuel B. 关键人员。请参阅说明。根据需要使用延续页面以如下所示的格式提供所需信息。 从首席研究员开始。按字母顺序列出所有其他关键人员，姓氏在前。 名称 eRA Commons 用户名 项目中的组织角色 嘿，Emanuel B. EMANUELHEY 罗格斯大学 PI 尼尔森，拉斯穆斯大学。哥本哈根 Co-Pi 其他重要贡献者 名称 组织在项目中的角色 人类胚胎干细胞 [x] 否 Q 是 如果拟议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。根据需要使用延续页面。 如果此时无法引用特定行，请包含将使用注册表中的行的声明。 细胞系 PHS 398（修订版 04/06）第 3 页 表格第 2 页 - 续 对接下来的页码进行连续编号 该应用程序。请勿使用 4a、4b 等后缀。 首席研究员/项目总监（最后、第一、中间）：嘿，Emanuel B 首席研究员/项目主管的姓名必须在每个打印页和每个续页的顶部提供。 研究资助 目录 页码 正面第 1 页 描述、表演地点、关键人员、其他重要贡献者和人力 胚胎干细胞 目录 初始预算期的详细预算（或模块化预算） 整个建议支持期的预算（不适用于模块化预算） na 与联合体/合同安排相关的预算（不适用于模块化预算） na 简历 - 首席研究员/项目总监（不超过四页） 其他传记概要（每项不超过四页 - 参见说明） 资源 12 研究计划，13 修订/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。） na A. 具体目标 Jl B. 背景和意义 17 C. 初步研究/进度报告（A-D 项：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（如果主页上的第 4 项标记为“是”则为必需） na 数据和安全监测计划（如果首页上的第 4 项标记为“是”且阶段 I、II、 或建议进行III期临床试验） na 纳入女性和少数族裔（如果主页上的第 4 项标记为“是”并且是临床研究，则为必填项） na 目标/计划入组表（用于新的和持续的临床研究） na 包含儿童（如果主页上的第 4 项标记为“是”，则为必填项） na F. 脊椎动物 na G. 选择代理研究 na H. 引用文献 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. 支持信（例如顾问） na 清单。 47 检查是否 附录（五套整理集。附录无需页码编号。） 附录是 包括 接受发表的出版物和手稿数量（不超过10篇） 其他项目（清单）： PHS 398（修订版 04/06）第 4 页 表格第 3 页