Molecular genetics of hybrid incompatibilities in Drosophila

描述(申请人提供)：这项工作的目的是确定当一个物种分裂成两个物种时发生的分子遗传变化。我们的长期目标是找到导致物种杂交死亡的基因，确定它们的功能，并推断它们的进化史。我们使用模式生物--黑腹果蝇的遗传工具，在与近缘物种--拟果蝇的杂交中进行作图实验。特别是，大量的致命性染色体缺失和功能丧失突变被用来在F1杂交雄性中通过互补来定位杂交死亡基因。在以前的工作中，通过与黑腹盘藻X染色体上的基因不相容的相互作用，鉴定了20个模拟盘藻常染色体基因组的小区域，这些小区域通过与黑腹盘藻X染色体上的基因不相容的相互作用而导致杂交不能。在这里，我们建议使用新的产生缺失的技术来在这些区域进行有针对性的重叠缺失，这将使我们能够将导致杂交无效的原因缩小到单个基因。我们将使用转基因实验来确认常染色体杂交死亡基因的身份，并鉴定它们的不相容的X连锁相互作用。一旦鉴定出杂交不存活基因，我们将研究DNA序列进化，以推断推动它们在物种之间功能分化的群体遗传力。这项工作将有助于我们理解包括人类在内的新动物物种是如何作为基因分化的副产品进化的。由于我们专注于杂交无活性，我们的一些工作将涉及表征以前未研究过的活性-基本基因和基因相互作用，这些基因具有包括人类在内的所有真核生物所需的功能。

DESCRIPTION (provided by applicant): The purpose of this work is to determine the molecular genetic changes that occur when one species splits into two species. Our long-term goals are to find genes that cause inviability in species hybrids, to determine their functions, and to infer their evolutionary histories. We use genetic tools from the model organism, Drosophila melanogaster, to perform mapping experiments in hybrids with the closely related species, D. simulans. In particular, the large collections of lethal chromosomal deletions and loss-of-function mutations from D. melanogaster are used to map hybrid inviability genes by complementation in F1 hybrid males. In previous work, 20 small regions of the D. simulans autosomal genome were identified that cause hybrid inviability via incompatible interactions with the genes on the D. melanogaster X chromosome. Here we propose to use new deletion-generating technology in D. melanogaster to make targeted, overlapping deletions in these regions that will allow us to narrow the cause hybrid inviability to single genes. We will use transgene experiments to confirm the identity of autosomal hybrid inviability genes and to identify their incompatible X-linked interactors. Once hybrid inviability genes are identified, we will study DNA sequence evolution to make inferences about the population genetic forces that drove their functional differentiation between species. This work will contribute to our understanding of how new animal species, including humans, evolve as a by-product of genetic divergence. Since we are concentrating on hybrid inviability, some of our work will involve characterizing previously unstudied viability-essential genes and gene interactions that have functions required in all eukaryotes, including humans.