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，比如不育或活力下降。这些问题是在物种形成期间和之后发生在每个物种中的不相容的遗传变化的结果。试图用传统的遗传方法找出这些基因变化是很困难的。然而，最近开发的分子方法允许研究人员在任何给定时间获得来自生物体的所有基因的基因活性快照（“微阵列”）提供了传统遗传方法的替代或补充，以揭示杂交不相容的遗传变化。我们将使用微阵列在一个经典的果蝇物种群中探索这个问题：伪盲果蝇（Drosophila pseudobscura）及其近亲persimilis和伪盲果蝇bogotana。我们将研究来自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，并将只跟踪与生殖有关的具有不寻常活性的基因。然后，我们将利用传统的遗传方法（即一系列遗传杂交）确定这些基因的一个子集是否确实与杂交不育有关。最后，我们将确定发生在这些基因或影响其活性的其他基因上的遗传变化是否确实是导致杂交不相容的原因。这种方法很可能为这些物种和其他物种的杂交不相容基因的身份提供重要的见解。拟议的研究结果将引起生物学家的普遍兴趣，并将使我们能够在功能基因组学和进化遗传学方面培训学生。我们完全致力于在我们的研究项目中整合来自代表性不足群体的个人。最后，在果蝇中发现假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，因此拟议的研究可能具有很大的健康意义。

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.