Molecular genetics of Drosophila hybrid lethality

果蝇杂交致死率的分子遗传学

• 批准号: 7490581
• 负责人: DANIEL A BARBASH
• 金额: $ 24.04万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490581
• 关键词: Address; Automobile Driving; Biological Assay; Biology; Class; Cloning; Codon Nucleotides; Development; Disease; Drosophila genus; Drosophila melanogaster; Evolution; Genes; Genetic Screening; Genetic Techniques; Genome; Genomics; Health; Human; Hybrids; Individual; Investigation; Knowledge; Lethal Genes; Modeling; Molecular; Molecular Evolution; Molecular Genetics; Mutation; Numbers; Organism; Pathology; Play; Population; Process; Property; Research Personnel; Role; Role playing therapy; Shapes; Siblings; Sister; Structure; System; Testing; Transgenic Organisms; base; comparative; design; gene function; genome sequencing; hybrid gene; loss of function; loss of function mutation; male; mutant; pressure; programs; reconstitution; reproductive; research study; trait

DESCRIPTION (provided by applicant): Recent studies suggest that positive selection is driving rapid divergence of genes involved in reproductive isolation between species. Detailed characterization of reproductive isolation genes will therefore contribute to our knowledge both of species-specific traits and adaptations and of the speciation process itself. We have) recently shown that the gene Hmr causes Fl hybrid lethality between Drosophila melanogaster and its sibling; species, and suggested that a second gene, Lhr, is also involved in this lethality. In Aim 1 of this proposal we propose to clone the Lhr gene in order to test the hypothesis that hybrid lethality is caused by the interaction of the D. melanogaster Hmr gene and the sibling-species Lhr gene. We will attempt to reconstitute the interspecific incompatibility entirely within /). melanogaster strains using transgenic constructs. We will also create a loss-of-function mutation in Lhr in D. melanogaster in order to understand the function of Lhr within species. Aim 2 will explore the relationship between the molecular evolution and the functional properties ct Hmr with respect to its intraspecific and hybrid functions. We will do developmental analyses of Hmr loss of- function mutants and of interspecific hybrids, use molecular evolutionary and population genetic techniques to identify regions and codons of Hmr that may be diverging under selection, and then use transgenic assays to test the functional consequences of hypotheses derived from these evolutionary analyses. We will also investigate whether Lhr has diverged under selection between D. melanogaster and its sibling species. In Aim 3 a genetic screen will be done in D. melanogaster to identify new genes that interact with Hmr and Lhr to cause hybrid lethality. The forthcoming whole-genome sequence from the sibling species D. simulans as well as several other Drosophila species will greatly enhance both the technical feasibility and the potential impact of this proposal as a model for testing functional consequences of sequence divergence.

描述（由申请人提供）：最近的研究表明，正选择正在推动物种间生殖隔离相关基因的快速分化。因此，生殖隔离基因的详细表征将有助于我们了解物种特异性特征和适应以及物种形成过程本身。我们最近发现，基因Hmr导致果蝇和它的同胞种之间的F1杂种致死性，并提出第二个基因Lhr也参与这种致死性。在目标1中，我们提出克隆Lhr基因，以验证杂种致死性是由D.黑腹果蝇Hmr基因和其近亲Lhr基因。我们将尝试重建种间不相容性完全内/）。使用转基因构建体的黑腹果蝇菌株。我们还将在D中的Lhr中创建功能缺失突变。为了了解Lhr在物种内的功能，目的2探讨Hmr的种内功能和杂交功能与分子进化的关系。我们将做HMR功能丧失突变体和种间杂种的发育分析，使用分子进化和群体遗传学技术，以确定区域和密码子的HMR，可能会分化下的选择，然后使用转基因检测来测试功能的后果来自这些进化分析的假设。我们还将调查Lhr是否在D.黑腹果蝇及其姊妹种在目标3中，将在D中进行遗传筛查。黑腹果蝇，以确定新的基因，相互作用的Hmr和Lhr，造成杂种致死。即将到来的兄弟物种D的全基因组序列。simulans以及其他几个果蝇物种的研究将大大提高这一提议作为测试序列分歧的功能后果的模型的技术可行性和潜在影响。