Identification and interpretation of introgressed hominin DNA in modern human genomes

现代人类基因组中渗入的古人类 DNA 的鉴定和解释

基本信息

  • 批准号:
    10606493
  • 负责人:
  • 金额:
    $ 33.37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-07-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Summary Over the past decade, advances in ancient DNA (aDNA) have provided striking new insights into human history, including conclusive proof that modern humans admixed with now extinct hominins, such as Neandertals and Denisovans. In the last cycle of funding, we pioneered methods to identify and interpret introgressed hominin DNA that still segregates in the genomes of modern humans. Analyses of these surviving archaic lineages shows that admixture among hominins was common, there was both positive and negative fitness consequences to gene flow, and introgressed sequences have functional and phenotypic effects. Despite these insights, there are many fundamentally important questions that remain to be addressed. The major barriers to a more comprehensive understanding of archaic hominin admixture include the need for further development of computationally efficient methods to find introgressed sequences, their application to more globally diverse populations, and experimental studies to delineate the molecular and functional consequences of gene flow. We will address each of these issues in the renewal project. Specifically, in Aim 1, we will extend and refine methods for identifying introgressed DNA sequences. Such further methodological development is necessary to improve power, reduce false positive rates, and be computationally efficient enough to analyze massively large sequencing data sets. In Aim 2, we will leverage our access to several large-scale sequencing projects and apply these novel methods to whole-genome sequence data from over 100,000 geographically diverse individuals. Importantly, by specifically constructing a diverse panel of individuals, particularly from understudied populations, we will be able to make inferences about archaic hominin admixture not previously possible. We will also develop methods to comprehensively analyze the population genetics characteristics of introgressed sequences and test hypotheses such as the fitness effects of admixture, sex-biased patterns of gene flow, and admixture with unknown (or “ghost”) lineages. Finally, in Aim 3, we will perform the first systematic and comprehensive experimental analysis of adaptively introgressed loci using cutting-edge gene editing and functional genomics technologies. The successful completion of the proposed project will extend our understanding of admixture events between archaic and modern humans, provide insight into how introgression has shaped extant patterns of human genomic diversity, and facilitate the molecular discovery and characterization of previously unknown archaic groups that have contributed to the modern gene pool.
总结

项目成果

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Joshua Michael Akey其他文献

Joshua Michael Akey的其他文献

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{{ truncateString('Joshua Michael Akey', 18)}}的其他基金

Project 2: Genetics of aging and longevity related traits in the domesticated dog
项目2:家养狗衰老和长寿相关性状的遗传学
  • 批准号:
    10213629
  • 财政年份:
    2018
  • 资助金额:
    $ 33.37万
  • 项目类别:
Project 2: Genetics of aging and longevity related traits in the domesticated dog
项目2:家养狗衰老和长寿相关性状的遗传学
  • 批准号:
    10440339
  • 财政年份:
    2018
  • 资助金额:
    $ 33.37万
  • 项目类别:
High resolution genetic dissection of complex and quantitative traits in yeast
酵母复杂和数量性状的高分辨率遗传解析
  • 批准号:
    9005198
  • 财政年份:
    2016
  • 资助金额:
    $ 33.37万
  • 项目类别:
High resolution genetic dissection of complex and quantitative traits in yeast
酵母复杂和数量性状的高分辨率遗传解析
  • 批准号:
    9893318
  • 财政年份:
    2016
  • 资助金额:
    $ 33.37万
  • 项目类别:
Fossil Free Sequencing of Archaic Genomes
古老基因组的无化石测序
  • 批准号:
    9250792
  • 财政年份:
    2014
  • 资助金额:
    $ 33.37万
  • 项目类别:
Fossil Free Sequencing of Archaic Genomes
古老基因组的无化石测序
  • 批准号:
    8874235
  • 财政年份:
    2014
  • 资助金额:
    $ 33.37万
  • 项目类别:
Developmental Patterning of the Anterior Neural Plate in a Simple Chordate
简单脊索动物前神经板的发育模式
  • 批准号:
    10796257
  • 财政年份:
    2014
  • 资助金额:
    $ 33.37万
  • 项目类别:
Comprehensively assessing human somatic variability and its influence on gene exp
全面评估人类体细胞变异及其对基因表达的影响
  • 批准号:
    8842674
  • 财政年份:
    2014
  • 资助金额:
    $ 33.37万
  • 项目类别:
Identification and interpretation of introgressed hominin DNA in modern human genomes
现代人类基因组中渗入的古人类 DNA 的鉴定和解释
  • 批准号:
    10211454
  • 财政年份:
    2014
  • 资助金额:
    $ 33.37万
  • 项目类别:
Comprehensively assessing human somatic variability and its influence on gene exp
全面评估人类体细胞变异及其对基因表达的影响
  • 批准号:
    8865430
  • 财政年份:
    2014
  • 资助金额:
    $ 33.37万
  • 项目类别:

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