Molecular genetics of Drosophila hybrid lethality

果蝇杂交致死率的分子遗传学

• 批准号: 7280786
• 负责人: DANIEL A BARBASH
• 金额: $ 24.14万
• 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/7280786
• 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，正向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。我们最近证明，Hmr 基因会导致果蝇及其同胞之间的 Fl 杂交致死；种，并表明第二个基因 Lhr 也与这种致死性有关。在本提案的目标 1 中，我们建议克隆 Lhr 基因，以检验杂交致死性是由黑腹果蝇 Hmr 基因和同胞物种 Lhr 基因相互作用引起的假设。我们将尝试完全在/)内重建种间不相容性。使用转基因构建体的黑腹果蝇菌株。我们还将在黑腹果蝇的 Lhr 中创建一个功能缺失突变，以了解 Lhr 在物种内的功能。目标 2 将探讨分子进化和功能特性 ct Hmr 的种内和杂合功能之间的关系。我们将对 Hmr 功能丧失突变体和种间杂种进行发育分析，使用分子进化和群体遗传技术来识别在选择下可能发生分歧的 Hmr 区域和密码子，然后使用转基因测定来测试假设的功能后果从这些进化分析中得出。我们还将研究 Lhr 是否在黑腹果蝇及其兄弟物种之间的选择下出现分歧。在目标 3 中，将在黑腹果蝇中进行遗传筛选，以确定与 Hmr 和 Lhr 相互作用从而导致杂交致死的新基因。即将推出的来自同胞物种 D. simulans 以及其他几种果蝇物种的全基因组序列将大大增强该提案作为测试序列分歧功能后果的模型的技术可行性和潜在影响。