Genetic control of recombination rate differences between Drosophila species

果蝇物种间重组率差异的遗传控制

基本信息

批准号：
8889697
负责人：
DAVEN C PRESGRAVES
金额：
$ 29.17万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-10 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8889697
关键词：
Accounting Affect Alleles Amino Acid Substitution Biological Assay Cell division Chromosome Mapping Chromosomes, Human, Pair 2 Code Complex DNA Binding Domain DNA Double Strand Break DNA Sequence Data Dissection Double Strand Break Repair Drosophila genus Event Evolution Female Gene Conversion Genes Genetic Genetic Crossing Over Genetic Recombination Genomics Genotype Goals Health Heteroduplex DNA Human Infertility Length Light MCM5 gene Maintenance Maps Mediating Meiosis Meiotic Recombination Messenger RNA Modeling Molecular Molecular Evolution Molecular Genetics Mutation N-terminal Phylogeny Population Genetics Probability Protein Region Proteins Recording of previous events Recurrence Relative (related person)Resolution Source System Testing Time Transgenes Transgenic Organisms Translating Work base cost effective egg experience fly genome sequencing genome-wide insight mutant next generation sequencing recombinational repair repaired research study species difference transmission process

项目摘要

DESCRIPTION (provided by applicant): The project proposed here will determine the molecular genetic control of evolved differences in the genomic recombination landscape between Drosophila species. The total genetic map of D. mauritiana is ~1.7 times longer than that of D. melanogaster-implying nearly twice as many crossovers per meiosis- and the extent of centromeric and telomeric suppression of crossing over is considerably smaller in D. mauritiana than D. melanogaster. In preliminary work, we showed that a dicistronic gene, mei-217/mei-218, has a history of recurrent adaptive evolution and mediates this evolved species difference in genetic map length. Here we propose to further investigate mei-217/mei-218 in three ways. First, we will functionally dissect the mei- 217/mei-218 gene, using interspecific chimeric transgene constructs, to determine which functional domains contribute to the evolutionary change in recombination rate. MEI-217 and MEI-218 have predicted DNA- binding domains and participate in a putative complex of minichromosome maintenance (MCM) proteins- along with MCM5 and REC/MCM8- required for the formation and/or stabilization of heteroduplex DNA crossover intermediates during meiotic recombination. Our functional dissection of mei-217/mei-218 may therefore shed light on how the gene products alter the probability of successful crossover formation. Second, we will use multiplexed next-generation sequencing to obtain and compare high-resolution genomic maps of crossing over and gene conversion between transgenic D. melanogaster genotypes that differ only in carrying either the D. melanogaster or D. mauritiana allele of mei-217/mei-218. With these data, we will determine the basis of species differences in the rate and distribution of crossover events. Finally, we will use our D. melanogaster system to assay the effects of functional divergence in mei-217/mei-218 to ask if recurrent substitutions in this rapidly evolving gene mediate changes in recombination rate in other Drosophila lineages.

描述（由申请人提供）：这里提出的项目将确定果蝇物种之间基因组重组景观进化差异的分子遗传控制。 D. mauritiana 的总遗传图谱比 D. melanogaster 长约 1.7 倍，这意味着每次减数分裂的交换次数几乎是 D. mauritiana 的两倍，并且 D. mauritiana 的着丝粒和端粒交换抑制程度比 D. melanogaster 小得多。黑腹果蝇。在前期工作中，我们发现双顺反子基因 mei-217/mei-218 具有反复适应性进化的历史，并介导这种进化的物种遗传图谱长度差异。在这里我们建议从三个方面进一步研究mei-217/mei-218。首先，我们将使用种间嵌合转基因构建体对 mei-217/mei-218 基因进行功能剖析，以确定哪些功能域有助于重组率的进化变化。 MEI-217 和 MEI-218 预测了 DNA 结合域，并参与了微染色体维持 (MCM) 蛋白的假定复合物，以及减数分裂过程中异源双链 DNA 交叉中间体的形成和/或稳定所需的 MCM5 和 REC/MCM8重组。因此，我们对 mei-217/mei-218 的功能剖析可能有助于揭示基因产物如何改变成功交叉形成的概率。其次，我们将使用多重下一代测序来获得并比较转基因黑腹果蝇基因型之间交换和基因转换的高分辨率基因组图谱，这些基因型的差异仅在于携带 mei-217 的黑腹果蝇或毛里求斯果蝇等位基因/mei-218。借助这些数据，我们将确定交叉事件发生率和分布的物种差异的基础。最后，我们将使用我们的黑腹果蝇系统来分析 mei-217/mei-218 中功能差异的影响，以询问该快速进化基因中的反复替换是否介导其他果蝇谱系的重组率变化。