Genome-Wide Screen for Candidate Genes Underlying Phenotypic Divergence and Hybrid Dysfunction in Drosophila Pseudoobscura and Its Close Relatives

了解新物种是如何形成的是生物学中的一个主要问题。当新物种从祖先进化而来时，它们的杂交后代通常会出现一些发育或生理问题，如不育或活力低下。这些问题是在物种形成期间和之后每个物种发生的不相容的遗传变化的结果。使用传统的遗传学方法很难确定这些基因变化是什么。然而，最近开发的分子方法，使研究人员获得在任何给定时间的生物体的所有基因的基因活性的快照（“微阵列”）提供了一种替代，或补充，传统的遗传方法，以揭示遗传变化的杂交不相容性。我们将使用微阵列在一组经典的果蝇物种中探索这个问题：拟暗果蝇及其近亲D。persimilis和D.拟暗花芹我们将调查这些物种的杂交不育雄性的基因活性，首先确定哪些基因具有不寻常的活性水平，并将只跟踪参与生殖的具有不寻常活性的基因。然后，我们将使用传统的遗传方法（即一系列遗传杂交）确定这些基因的子集是否确实参与杂种不育。最后，我们将确定发生在这些基因或其他影响其活性的基因上的遗传变化是否确实是杂种不亲和性的原因。这种方法可能会提供主要的洞察到负责在这些和其他组的物种的杂交不相容性的基因的身份。这项研究的结果将引起生物学家的普遍兴趣，并使我们能够在功能基因组学和进化遗传学方面培训学生。我们完全致力于将来自代表性不足的群体的个人融入我们的研究计划。最后，在果蝇中鉴定推定的杂交雄性不育基因可能会导致发现与人类雄性不育有关的类似基因，因此拟议研究的健康意义可能很大。

Understanding how new species are formed is a major question in Biology. When new species evolve from an ancestral one, their hybrids usually have several developmental or physiological problems, like infertility or lower vigor. Those problems are the result of incompatible genetic changes that have occurred in each one of the species during and after speciation. Trying to pinpoint what are those genetic changes has been difficult using traditional genetic methods. However, recently developed molecular methods that allow investigators obtain a snapshot of gene activity in all genes from an organism at any given time ("microarrays") provide an alternative, or complement, to traditional genetic methods to uncover the genetic changes underlying hybrid incompatibilities. We will use microarrays to explore this question in a classic group of fruit fly species: Drosophila pseudoobscura and its close relatives D. persimilis and D. pseudoobscura bogotana. We will investigate gene activity in hybrid sterile males from those species to first determine what genes have unusual levels of activity and will follow up only genes with unusual activity that are involved in reproduction. We will then establish whether a subset of those genes is indeed involved in hybrid sterility using traditional genetic methods (i.e. a series of genetic crosses). Finally, we will determine whether genetic changes that have occurred at those genes or at other genes that affect their activity are indeed responsible for the hybrid incompatibilities. This approach is likely to provide major insights into the identity of genes responsible for hybrid incompatibilities in these and other group of species. The results of the proposed research will be of general interest to biologists and will allow us training students in functional genomics and evolutionary genetics. We are fully committed to integrate individuals from underrepresented groups in our research program. Finally, the identification of putative hybrid male sterility genes in Drosophila could lead to the discovery of similar genes also involved in human male infertility, and thus the health implications of the proposed research may be large.