Effects of genetic background on adaptive evolution

遗传背景对适应性进化的影响

基本信息

  • 批准号:
    10615639
  • 负责人:
  • 金额:
    $ 32.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Project Summary To what extent is adaptive evolution predictable? Despite its importance in understanding the biology of human diseases, including the evolution of viral and bacterial pathogens, the dynamics of genetic adaptation are still poorly understood. In particular, few examples yet exist that have been dissected to the molecular level. Examples of adaptations from natural systems and the use of model organisms are powerful tools that can be combined to make progress on this difficult question. We have employed instances of “parallel evolution”, involving assemblages of species experiencing a common regime of natural selection, to evaluate multiple outcomes of the process of adaptation. With this information, we can learn about recurrent features of adaptation and infer constraints and regularities in the adaptive process. Our work focused on the biomedically-important interaction between Na+,K+-ATPases and their regulatory steroidal-glycosides that a large variety of plants and animals use as toxins to defend themselves from being eaten. Using a diverse set of animals that have independently evolved resistance to steroidal-glycoside toxicity, including insects and vertebrates, we discovered these diverse species most often evolve resistance via a small number of possible options (i.e. involving only three of 41 possible sites in the protein that could be modified to confer resistance). These findings suggest that adaptive evolution is often path-dependent, implying that the individual components of an adaptation must evolve in a prescribed, and ultimately predictable, order. They also raise numerous questions about the nature of this path dependency, including the extent to which it emerges from interactions among residues within a protein, or from the genomic background of the species; whether it similarly constrains adaptation over short and longer time scales, and how generally it applies in adaptive protein evolution. Here we propose three aims that address these questions, by combining approaches from evolutionary genomics and molecular genetics. In Aim 1, we will use genome engineering in Drosophila to elucidate the path dependence of the steroidal-glycoside resistance adaptation both at the level of its primary target (Na+,K+-ATPase) and at the level of the whole genome. In Aim 2, we will determine which and how many genomic factors contribute to naturally occurring variation within Drosophila populations. This information will reveal the relationship between within- population and between-species genetic variation underlying the same trait, connecting short- and long-term dynamics of the adaptive process. In Aim 3, we will use principles learned from molecular adaptation at Na+,K+-ATPase to computationally predict and use genome engineering to functionally validate path dependent adaptation dynamics in Drosophila for a diverse group of proteins, many of which (like Na+,K+-ATPase) have important roles in neurological development and homeostasis. Together this work will greatly increase our understanding of the constraints on adaptive protein evolution and the predictability of the genetic changes by which novel phenotypes emerge.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Peter Andolfatto其他文献

Peter Andolfatto的其他文献

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{{ truncateString('Peter Andolfatto', 18)}}的其他基金

The evolution of a co-opted gene-regulatory network underlying a rapidly evolving morphological trait
快速进化的形态特征背后的增选基因调控网络的进化
  • 批准号:
    9920412
  • 财政年份:
    2019
  • 资助金额:
    $ 32.96万
  • 项目类别:
The evolution of a co-opted gene-regulatory network underlying a rapidly evolving morphological trait
快速进化的形态特征背后的增选基因调控网络的进化
  • 批准号:
    9103364
  • 财政年份:
    2016
  • 资助金额:
    $ 32.96万
  • 项目类别:
The evolution of a co-opted gene-regulatory network underlying a rapidly evolving morphological trait
快速进化的形态特征背后的增选基因调控网络的进化
  • 批准号:
    9477041
  • 财政年份:
    2016
  • 资助金额:
    $ 32.96万
  • 项目类别:
Dissecting the molecular basis and assembly of a complex morphological trait
剖析复杂形态特征的分子基础和组装
  • 批准号:
    9211338
  • 财政年份:
    2015
  • 资助金额:
    $ 32.96万
  • 项目类别:
Effects of genetic background on adaptive evolution
遗传背景对适应性进化的影响
  • 批准号:
    10397123
  • 财政年份:
    2015
  • 资助金额:
    $ 32.96万
  • 项目类别:
Dissecting the molecular basis and assembly of a complex morphological trait
剖析复杂形态特征的分子基础和组装
  • 批准号:
    8861499
  • 财政年份:
    2015
  • 资助金额:
    $ 32.96万
  • 项目类别:
Adaptive evolution of non coding DNA and gene expression divergence in Drosophila
果蝇非编码DNA的适应性进化和基因表达差异
  • 批准号:
    8514007
  • 财政年份:
    2009
  • 资助金额:
    $ 32.96万
  • 项目类别:
Adaptive evolution of non coding DNA and gene expression divergence in Drosophila
果蝇非编码DNA的适应性进化和基因表达差异
  • 批准号:
    8303418
  • 财政年份:
    2009
  • 资助金额:
    $ 32.96万
  • 项目类别:
Adaptive evolution of non coding DNA and gene expression divergence in Drosophila
果蝇非编码DNA的适应性进化和基因表达差异
  • 批准号:
    7920943
  • 财政年份:
    2009
  • 资助金额:
    $ 32.96万
  • 项目类别:
Adaptive evolution of non coding DNA and gene expression divergence in Drosophila
果蝇非编码DNA的适应性进化和基因表达差异
  • 批准号:
    8114194
  • 财政年份:
    2009
  • 资助金额:
    $ 32.96万
  • 项目类别:

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