Molecular genetics of hybrid incompatibilities in Drosophila

描述（由申请人提供）：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无法生存的基因，确定它们的功能，并推断它们的进化历史。我们使用来自模式生物——黑腹果蝇的遗传工具，在与密切相关的物种——D. simulans的杂交中进行了定位实验。特别是，大量的致命染色体缺失和功能缺失突变被用于通过在F1杂交雄性中互补来定位杂种不生存基因。在之前的研究中，研究人员鉴定出了模拟海蛞蝓常染色体基因组中的20个小区域，这些区域通过与黑腹海蛞蝓X染色体上的基因不相容的相互作用导致了杂交不育。在这里，我们建议使用新的缺失生成技术在D. melanogaster中制造有针对性的，重叠的缺失，这将使我们能够将导致杂交不育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无活力基因的身份，并确定其不相容的x连锁相互作用体。一旦杂交不育基因被确定，我们将研究DNA序列进化，以推断驱动其在物种之间功能分化的群体遗传力量。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遗传分化的副产品而进化的。由于我们专注于杂交的不生存能力，我们的一些工作将涉及表征以前未研究的生存能力必需基因和基因相互作用，这些基因在包括人类在内的所有真核生物中都具有所需的功能。

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.