Molecular Genetics of Drosophila Hybrid Lethality

描述（由申请人提供）：当不同的种群在繁殖上被隔离时，新物种就形成了。造成这种分离的一个原因是杂种不亲和性、种间杂种的不育性和致死率。本研究研究了两个先前确定的基因，它们相互作用导致黑腹果蝇和拟象果蝇之间的杂交致死。对这两个基因的序列分析表明，它们是在适应进化下进化的，这一模式也适用于其他杂交不亲和性基因。因此，确定导致这种分子进化模式的特定选择力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，这些果蝇杂交不相容基因需要抑制转座因子，自私的dna，可以调动，达到高拷贝数，并对真核生物基因组造成重大损害。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因子中起作用，包括在突变系中分析转座的全基因组模式。其他表型分析将研究这些基因如何影响其宿主物种的育性和减数分裂性能。然后，注意力将转向一个综合的努力，以确定物种之间的序列分化和适应性进化如何改变了这些基因的特定功能。转座因子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。所提出的研究将提供一个高分辨率的观点，如何转座因子负荷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.