Genetic control of recombination rate differences between Drosophila species

果蝇物种间重组率差异的遗传控制

• 批准号: 8744433
• 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
• 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/8744433
• 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; 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; public health relevance; recombinational repair; repaired; research study; species difference; transmission process

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）：