Fine-scale recombination, variation, divergence, and codon bias in Drosophila

果蝇中的精细重组、变异、分歧和密码子偏倚

• 批准号: 8246526
• 负责人: RICHARD M KLIMAN
• 金额: $ 26.76万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-06 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8246526
• 关键词: Address; Affect; Base Sequence; Biological Models; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 20; Codon Nucleotides; Conflict (Psychology); DNA Sequence; Data; Drosophila genus; Drosophila melanogaster; Evaluation; Evolution; Genetic; Genetic Recombination; Genome; Health; Heterogeneity; Housekeeping Gene; Human; Influentials; Inherited; Measures; Meiotic Recombination; Metabolic; Modeling; Molecular; Mus; Mutation; Natural Selections; Nature; Nucleotides; Pan Genus; Pattern; Population Sizes; Process; Reporting; Research; Research Personnel; Resolution; Resources; Tomatoes; Variant; Work; experience; genome sequencing; human disease; interdisciplinary approach; success

DESCRIPTION (provided by applicant): One of the most influential findings of the last 20 years in molecular evolutionary studies has been that recombination rate is frequently correlated with nucleotide sequence diversity within a species. In Drosophila species, this relationship has been attributed to natural selection, while neutral causes have been attributed as primary contributors to this association in humans. However, the relationship of recombination to diversity has not been observed in all species examined, and conflicting reports also exist on whether recombination rate is associated with interspecies sequence divergence or codon usage bias. If there is fine-scale heterogeneity in recombination rate across a genome, the conflicting conclusions could result from differences in the scale with which recombination is measured. Additionally, interpreting the evolutionary causes of these associations to recombination rate can be facilitated by evaluations at multiple scales. This proposal takes a collaborative and interdisciplinary approach to tackling these oft- cited relationships. Building upon a successful preliminary study, the investigators will construct very high resolution linkage maps using the species Drosophila pseudoobscura, and correlate local recombination rates to various sequence motifs. They will also generate multiple whole-genome sequence assemblies of this species from which to carefully examine patterns of nucleotide diversity at an unprecedented scale. Finally, extensive modeling is proposed to examine possible effects of background selection and selective sweeps to infer conditions under which they can operate to produce the observed associations between recombination rate and diversity, divergence, or codon bias. The investigators have extensive experience with all of the proposed work, as illustrated by the preliminary results reported. PUBLIC HEALTH RELEVANCE: Drosophila fruit flies and humans likely share many metabolic housekeeping genes and thus could experience similar absolute selection coefficients. Because humans have a much smaller population size, we accumulate many detrimental mutations that would be eliminated in Drosophila, so quantifying the contributions of such classes of mutations to genome evolution using a model system could potentially inform the rate of accumulation of hereditary human diseases.

描述（由申请人提供）：分子进化研究中过去20年中最有影响力的发现之一是重组率经常与物种内的核苷酸序列多样性相关。在果蝇物种中，这种关系归因于自然选择，而中性原因则归因于人类这种关联的主要贡献者。但是，在所有检查的物种中尚未观察到重组与多样性的关系，并且还存在有关重组率是否与种间序列差异或密码子使用偏见相关的报道。如果基因组重组率的重组率很高，则可能是由于测量重组的规模差异而产生的相互矛盾的结论。此外，将这些关联的进化原因解释为重组率，可以通过多个尺度的评估来促进。该建议采用协作和跨学科的方法来解决这些经常引用的关系。在一项成功的初步研究的基础上，研究人员将使用果蝇假性物种构建非常高的分辨率连锁图，并将局部重组率与各种序列基序相关联。它们还将生成该物种的多个全基因组序列组件，以仔细检查核苷酸多样性的模式，以前所未有的规模。最后，提出了广泛的建模，以检查背景选择和选择性扫描的可能影响，以推断他们可以在这些条件下进行操作以产生重组率与多样性，发散或密码子偏见之间的观察到的关联。如报告的初步结果所示，研究人员在所有提议的工作中都有丰富的经验。公共卫生相关性：果蝇果蝇和人类可能具有许多代谢管家基因，因此可能会经历类似的绝对选择系数。由于人的人口规模较小，因此我们积累了许多有害突变，这些突变将在果蝇中消除，因此使用模型系统量化了此类突变对基因组进化的贡献，可能会导致遗传性人类疾病的积累率。

项目成果

PseudoBase: a genomic visualization and exploration resource for the Drosophila pseudoobscura subgroup

• DOI: 10.1080/19336934.2020.1864201
• 发表时间: 2020-12
• 期刊: Fly
• 影响因子: 1.2
• 作者: Katharine L Korunes;Russell B. Myers;Ryan Hardy;M. Noor

How big is your Y? A genome sequence-based estimate of the size of the male-specific region in Megaselia scalaris.

你的Y有多大？

• DOI: 10.1534/g3.114.015057
• 发表时间: 2014
• 期刊: G3 (Bethesda, Md.)
• 作者: Hoehn,KennethB;Noor,MohamedAF
• 通讯作者: Noor,MohamedAF

Recombination modulates how selection affects linked sites in Drosophila.

• DOI: 10.1371/journal.pbio.1001422
• 发表时间: 2012
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: McGaugh SE;Heil CS;Manzano-Winkler B;Loewe L;Goldstein S;Himmel TL;Noor MA
• 通讯作者: Noor MA

Witnessing Phenotypic and Molecular Evolution in the Fruit Fly.

见证果蝇的表型和分子进化。

• DOI: 10.1007/s12052-012-0447-5
• 发表时间: 2012
• 期刊: Evolution
• 影响因子: 3.3
• 作者: Heil,CaitiSS;Hunter,MikaJ;Noor,JulietKf;Miglia,Kathleen;Manzano-Winkler,Brenda;McDermott,ShannonR;Noor,MohamedAf
• 通讯作者: Noor,MohamedAf