Towards a general theory of evolutionary capacitance

走向进化电容的一般理论

基本信息

批准号：
7898200
负责人：
JOANNA MASEL
金额：
$ 9.64万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-13 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7898200
关键词：
3&apos Untranslated Regions Address Adverse effects Affect Alleles Alternative Splicing Arabidopsis Architecture Assimilations Biology Code Complement Complex Computing Methodologies DNA Transposable Elements Data Dependence Disease Drosophila genus Electric Capacitance Equilibrium Event Evolution Exhibits Frequencies Future Gene Conversion Generations Genes Genetic Genetic Drift Genetic Population Study Genetic Processes Genetic Recombination Genetic Variation Genomics Heat shock proteins Human Inherited Left Life Mediating Methods Modeling Molecular Mutation Natural Selections Nature Organism Pathway interactions Phase Phenotype Point Mutation Population Population Genetics Population Sizes Principal Investigator Probability Process Property Protein Structure Initiative Public Health Relative (related person)Research Personnel Role SOS Response Signal Transduction Site Solid Staging Stroke Surveys System Taxon Terminator Codon Testing Time Transducers Translations Untranslated Regions Variant Work Yeasts base chromatin modification comparative cost environmental change genetic analysis human disease improved loss of function model development mutant novel preconditioning pressure programs protein aggregate research study theories tool trait yeast prion

项目摘要

DESCRIPTION (provided by applicant): Evolutionary capacitor mechanisms such as the yeast prion [PSI+] and the heat shock protein HspQO store variation in a latent form and reveal it later. Capacitors appear to be common, and could be key components of genetic architecture. Capacitors help explain why a disease allele in 1 genetic and environmental context could be harmless in a different context. Perhaps because the biology of capacitance is substantially different from the mutation, recombination, and selection processes typically studied by population genetics, capacitors remain poorly understood from a theoretical perspective. The proposed work will develop a novel population genetics theory to capture the essence of capacitor biology in a finite population undergoing rare environmental change events. The theory will focus on the invasion probabilities of alleles that modify the probability with which variation is revealed. The theory will be used to predict the circumstances under which such alleles will be favored. It will incorporate unusual aspects of capacitor biology, such as the fact that variation is revealed at multiple sites simultaneously, and that revelation is easily reversible. Another unusual aspect of capacitor biology is that hidden variation may be subject to low levels of selection rather than no selection. Mild selection in the hidden state, by removing strongly deleterious mutants, may enrich hidden variation for potentially adaptive traits. This phenomenon of preadaptation will be incorporated into the model framework and its impact on capacitor-mediated adaptation will be assessed. The theoretical framework for capacitance will be reinforced by using comparative yeast genomics of 3' untranslated regions to survey the evidence for past [PSI+] capacitance activity and for preadaptation of the variation revealed by [PSI+]. In the context of public health, the complex genetic architecture of human disease often confounds attempts at genetic analysis. A solid understanding of evolutionary capacitance may provide a new framework for such analyses in the future. Since direct experiments on capacitance cannot be performed in humans, the theoretical and predictive approach described here is particularly important for understanding the scope of capacitance in explaining human variation.

描述（由申请人提供）：诸如酵母朊病毒[PSI+]和热休克蛋白HspQO之类的进化电容器机制以潜在形式存储变异并在以后揭示它。电容器似乎很常见，并且可能是遗传结构的关键组成部分。电容器有助于解释为什么在一种遗传和环境背景下的疾病等位基因在不同的背景下可能是无害的。也许是因为电容的生物学特性与群体遗传学通常研究的突变、重组和选择过程有很大不同，所以从理论角度来看，人们对电容器仍然知之甚少。拟议的工作将开发一种新颖的群体遗传学理论，以捕捉经历罕见环境变化事件的有限群体中电容器生物学的本质。该理论将重点关注等位基因的入侵概率，这些概率会改变揭示变异的概率。该理论将用于预测在什么情况下这些等位基因会受到青睐。它将结合电容器生物学的不寻常方面，例如在多个位点同时揭示变异的事实，并且这种揭示很容易逆转。电容器生物学的另一个不寻常的方面是，隐藏的变异可能会受到低水平的选择而不是没有选择。通过去除强烈有害的突变体，隐藏状态下的温和选择可能会丰富潜在适应性特征的隐藏变异。这种预适应现象将被纳入模型框架中，并将评估其对电容器介导的适应的影响。通过使用 3' 非翻译区域的比较酵母基因组学来调查过去 [PSI+] 电容活性的证据以及 [PSI+] 揭示的变异的预适应，将强化电容的理论框架。在公共卫生背景下，人类疾病复杂的遗传结构常常使遗传分析的尝试陷入困境。对演化电容的深入理解可能为未来的此类分析提供新的框架。由于无法在人类身上进行直接电容实验，因此此处描述的理论和预测方法对于理解电容范围以解释人类差异特别重要。