Molecular Genetics of Drosophila Hybrid Lethality

描述(由申请人提供)：当不同的种群变得生殖隔离时，新物种形成。这种隔离的一个原因是杂交不亲和性，种间杂交的不育性和致命性。这项建议调查了两个先前发现的基因，它们相互作用，导致果蝇物种黑腹果蝇和拟果蝇杂交的致命性。对这两个基因的序列分析表明，它们是在适应性进化下进化的，这一模式也在其他杂交不亲和基因中观察到。因此，确定导致这种分子进化模式的特定选择力量将有助于阐明物种形成的生物学原因。这一建议是基于最近的发现，即这些果蝇杂交不亲和基因需要抑制转座元件，自私的DNA可以动员，达到高拷贝数，并对真核基因组造成重大破坏。这里提出了一系列的遗传和分子分析来确定这些基因如何在抑制转座元件方面发挥作用，包括描绘突变系中转座的全基因组模式。其他表型分析将调查这些基因如何影响它们自己寄主物种的繁殖力和减数分裂表现。然后，人们的注意力将转向综合努力，以确定物种之间的序列分歧和适应性进化如何改变这些基因的特定功能。转座元件是包括人类在内的真核生物自发突变和DNA损伤的主要原因。拟议的研究将提供一个高分辨率的观点，即转座元件负载如何有助于宿主基因进化和物种之间的生殖隔离。

DESCRIPTION (provided by applicant): New species form when diverging populations become reproductively isolated. One cause of this isolation is hybrid incompatibility, the sterilit and lethality of interspecific hybrids. This proposal investigates two previously identified genes that interact to cause lethality in hybrids between the fruit fly species Drosophila melanogaster and D. simulans. Sequence analysis of both genes shows that they have evolved under adaptive evolution, a pattern also observed with other hybrid incompatibility genes. Identifying the specific selective forces causing this pattern of molecular evolution will therefore help elucidate the biological causes of speciation. This proposal is based on the recent discovery that these Drosophila hybrid incompatibility genes are required to repress transposable elements, selfish DNAs that can mobilize, reach high copy number, and cause significant damage to eukaryotic genomes. A range of genetic and molecular assays are proposed here to identify how these genes function in repressing transposable elements, including profiling the genome-wide pattern of transposition in mutant lines. Other phenotypic assays will investigate how these genes affect fertility and meiotic performance within their own host species. Attention will then turn to an integrated effort to determine how sequence divergence and adaptive evolution between species has altered specific functions of these genes. Transposable elements are a major cause of spontaneous mutation and DNA damage in eukaryotes including humans. The proposed studies will provide a high resolution view of how transposable element load contributes to host gene evolution and reproductive isolation between species.