Evolution of the Genome-wide Recombination Rate in Mice
Evolution of the Genome-wide Recombination Rate in Mice
批准号:
9896869
负责人:
Bret A Payseur
金额:
$59.04万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-05-15 至 2022-03-31
关键词:
Animal ModelBiologicalChromosomesCytologyDNADNA Double Strand BreakDefectDevelopmental DisabilitiesDiseaseEnsureEvolutionFemaleGametogenesisGenerationsGeneticGenetic EnhancementGenetic PolymorphismGenetic RecombinationGenetic VariationGenomeGenomicsGeographyHealthHeritabilityHouse miceHumanImmunofluorescence ImmunologicIndividualLeadLinkMeasuresMeiosisMolecularMusMutationNatural SelectionsNatureOogenesisPathway interactionsPatternPhenotypePopulationPortraitsProcessRegulationResearchRoleSpermatogenesisSpontaneous abortionSynaptonemal ComplexTestingVariantbiological sexeggexperiencefetal lossgenetic profilinggenome-wideinter-individual variationmalepressurerepairedsexsperm celltrait
中文摘要
项目摘要
减数分裂期间的减数分裂具有多种生物学作用。进化通过改组使基因组多样化
突变的组合,从而增加遗传变异和提高自然的效率,
选择.在许多物种中,重组也确保染色体在重组过程中正确分离。
配子发生虽然这些作用应该对重组施加强的选择性限制,
重组率因个体而异。这一意外的结果提出了一个尚未回答的主要问题:
在自然界中,什么过程控制着复合率的变化?
重要的是,我们仍然缺乏一个基本的图片,如何遗传组成部分的重组率变化,
物种之间的差异-了解任何表型如何进化所需的信息。两条线索
自然变异的潜在决定因素来自最近针对重组机制的研究。
首先,两性呈现出截然不同的重组景观和减数分裂限制,
预测男性和女性将显示个体间变异的不一致模式。二是
新的证据表明,DNA双链断裂的数量和断裂修复的比例,
杂交也显示了个体间的差异,这表明这些特征可以解释自然变异。
重组率。
拟议中的研究将提供急需的重组率自然遗传变异的画像
跨越多个进化尺度。性别和关键减数分裂过程对变异的贡献
将评估个体之间的重组率。在目标1中,我们将测量多态性,
在卵子发生和精子发生过程中全基因组重组率的分歧,
免疫荧光细胞学检查。性别特异性,遗传变异的总数,
交叉将使用一组家鼠及其
亲戚预测重组率经历不同的进化压力,在这两个
将通过在常见基因组中对雌性和雄性进行对照比较来测试性别。
背景在目标2中,我们将使用免疫荧光细胞学来描绘自然遗传变异,
导致交叉的分子过程,包括双链断裂的产生,
的重组中间体,和组装的联会复合体。通过将这些特征与
在同一组菌株中的交叉总数,我们将检验以下假设:
交叉和非交叉修复是重组率进化的主要因素。
重组缺陷是胎儿丢失的主要原因,也是发育不良的主要遗传原因。
人类的残疾。通过研究重组率的遗传变异及其潜在的决定因素,
家鼠的自然种群-重组相关疾病的模式生物-该项目
与人类健康有关。
英文摘要
PROJECT SUMMARY
Recombination during meiosis serves multiple biological roles. Recombination diversifies genomes by shuffling
combinations of mutations, thereby increasing genetic variation and enhancing the efficiency of natural
selection. In many species, recombination also ensures that chromosomes segregate properly during
gametogenesis. Although these roles should impose strong selective constraints on recombination,
recombination rate varies among individuals. This unexpected result raises a major unanswered question:
what processes govern variation in recombination rate in nature?
Importantly, we still lack a basic picture of how the heritable component of recombination rate varies within and
between species – information that is required for understanding how any phenotype evolves. Two clues about
potential determinants of natural variation come from recent studies targeting recombination mechanisms.
First, the two sexes present contrasting recombination landscapes and meiotic constraints, raising the
prediction that males and females will display discordant patterns of inter-individual variation. Second, there is
new evidence that the number of DNA double-strand breaks and the proportion of breaks repaired as
crossovers also show differences among individuals, suggesting that these traits could explain natural variation
in recombination rate.
The proposed research will provide a much-needed portrait of natural genetic variation in recombination rate
across multiple evolutionary scales. The contributions of sex and key meiotic processes to variation in
recombination rate among individuals will be evaluated. In Aim 1, we will measure polymorphism and
divergence in the genome-wide recombination rate during oogenesis and spermatogenesis by applying
immunofluorescence cytology to individual mice. Sex-specific, genetic variation in the total number of
crossovers will be quantified on geographically global and local scales using a panel of house mice and their
relatives. The prediction that recombination rate experiences distinctive evolutionary pressures in the two
sexes will be tested through controlled comparisons between females and males across common genomic
backgrounds. In Aim 2, we will use immunofluorescence cytology to profile natural genetic variation in
molecular processes that lead to crossovers, including the generation of double-strand breaks, the regulation
of recombination intermediates, and the assembly of the synaptonemal complex. By linking these traits to the
total number of crossovers in the same set of strains, we will test the hypothesis that the decision between
crossover and non-crossover repair is a primary factor in recombination rate evolution.
Defects in recombination are a leading cause of fetal loss and a leading genetic cause of developmental
disabilities in humans. By examining heritable variation in recombination rate and its potential determinants in
natural populations of the house mouse – a model organism for recombination-related disorders – this project
is relevant to human health.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
Evolution of Phenotypic Extremes and Mechanisms Governing Inheritance
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批准号:10084060
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项目类别:
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资助金额:$97.04万
-
财政年份:2021
-
负责人:Bret A Payseur
-
依托单位:
Evolution of Phenotypic Extremes and Mechanisms Governing Inheritance
-
批准号:10375351
-
项目类别:
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资助金额:$97.11万
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财政年份:2021
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负责人:Bret A Payseur
-
依托单位:
Evolution of Phenotypic Extremes and Mechanisms Governing Inheritance
-
批准号:10593140
-
项目类别:
-
资助金额:$97.11万
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财政年份:2021
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负责人:Bret A Payseur
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依托单位:
The Genetics and Evolution of Extreme Body Size in Mice from Gough Island
-
批准号:8541868
-
项目类别:
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资助金额:$36.67万
-
财政年份:2012
-
负责人:Bret A Payseur
-
依托单位:
The Genetics and Evolution of Extreme Body Size in Mice from Gough Island
-
批准号:8370621
-
项目类别:
-
资助金额:$54.29万
-
财政年份:2012
-
负责人:Bret A Payseur
-
依托单位:
The Genetics and Evolution of Extreme Body Size in Mice from Gough Island
-
批准号:8675265
-
项目类别:
-
资助金额:$38.0万
-
财政年份:2012
-
负责人:Bret A Payseur
-
依托单位:
Integrating SNPs and STRPs in Population Genetics
-
批准号:7906032
-
项目类别:
-
资助金额:$28.52万
-
财政年份:2008
-
负责人:Bret A Payseur
-
依托单位:
Integrating SNPs and STRPs in Population Genetics
-
批准号:7674019
-
项目类别:
-
资助金额:$28.33万
-
财政年份:2008
-
负责人:Bret A Payseur
-
依托单位:
Integrating SNPs and STRPs in Population Genetics
-
批准号:8118279
-
项目类别:
-
资助金额:$28.21万
-
财政年份:2008
-
负责人:Bret A Payseur
-
依托单位:
Integrating SNPs and STRPs in Population Genetics
-
批准号:7523320
-
项目类别:
-
资助金额:$27.5万
-
财政年份:2008
-
负责人:Bret A Payseur
-
依托单位:
Integrating SNPs and STRPs in Population Genetics
-
批准号:8324745
-
项目类别:
-
资助金额:$28.19万
-
财政年份:2008
-
负责人:Bret A Payseur
-
依托单位:
海外基金