DETECTING ADAPTIVE EVOLUTION IN THE CONTEXT OF LINKED DELETERIOUS MUTATIONS

检测连锁有害突变背景下的适应性进化

• 批准号: 8549266
• 负责人: Justin C Fay
• 金额: $ 18.34万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-22 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549266
• 关键词: Affect; Alleles; Computer Simulation; DNA; Event; Evolution; Frequencies; Genes; Genetic Polymorphism; Genetic Recombination; Genome; Genomics; Goals; Health; Human; Lead; Link; Linkage Disequilibrium; Measures; Methods; Molecular Evolution; Mutation; Organism; Pathogenesis; Pattern; Play; Population; Population Sizes; Recording of previous events; Research; Risk; Role; Testing; Variant; design; disease-causing mutation; genome sequencing; high reward; high risk; microbial; sample fixation; theories

DESCRIPTION (provided by applicant): Our understanding of molecular evolution depends on our ability to identify adaptive substitutions and estimate their frequency in the genome. Numerous statistical tests of neutrality have been developed to detect adaptive evolution and application of these tests to genome sequence variation has provided strong evidence against the neutral theory of molecular evolution. Yet, our ability to detect positive selection and estimate its frequency in the genome may be unknowingly affected by deleterious mutations. First, the spread of an advantageous allele through a population may cause the fixation of linked deleterious mutations, leading to overestimates of the frequency of adaptive substitution. Second, deleterious mutations may interfere with the spread of an advantageous allele through a population, leading to altered patterns of linked neutral variation. The goal of the proposed research is to use computer simulations to investigate the conditions under which deleterious mutations significantly alter our ability to identify and estimate the frequency of adaptive evolution.

描述（由申请人提供）： 我们对分子进化的理解取决于我们识别适应性取代并估计其在基因组中频率的能力。许多中性的统计测试已经开发出检测适应性进化和应用这些测试的基因组序列变异提供了强有力的证据对中性理论的分子进化。然而，我们检测积极选择并估计其在基因组中频率的能力可能会在不知不觉中受到有害突变的影响。首先，有利等位基因在群体中的传播可能会导致连锁有害突变的固定，导致高估适应性取代的频率。第二，有害突变可能会干扰有利等位基因在群体中的传播，导致连锁中性变异模式的改变。这项研究的目的是使用计算机模拟来研究有害突变显著改变我们识别和估计适应性进化频率的能力的条件。