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

果蝇及其近亲表型分化和杂种功能障碍的候选基因的全基因组筛选

• 批准号: 0941217
• 负责人: Carlos Machado
• 金额: $ 9.18万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0941217&HistoricalAwards=false
• 关键词: Genome; Wide; Screen; Candidate; Genes

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.

了解新物种的形成是生物学的主要问题。当新物种从祖先发展时，它们的杂种通常会出现多个发育或生理问题，例如不育或较低的活力。这些问题是物种形成期间和之后的每个物种中发生的不相容的遗传变化的结果。试图通过传统的遗传方法来查明这些遗传变化是什么是困难的。然而，最近开发的分子方法允许研究人员在任何给定时间（“微阵列”）从生物体中获得所有基因的基因活性快照（“微阵列”）为传统的遗传学方法提供了一种替代性或补充，以发现杂种不兼容性的基本变化。我们将使用微阵列在经典的果蝇物种中探索这个问题：果蝇pseudoobscura及其近亲D. Persimilis和D. Pseudoobscura Bogotana。我们将研究来自这些物种的杂交无菌雄性的基因活性，以首先确定哪些基因具有异常的活性水平，并且只会跟踪与繁殖有关的非同寻常活性的基因。然后，我们将使用传统的遗传学方法（即一系列遗传杂交）确定这些基因的子集是否确实参与了杂化不育。最后，我们将确定在那些基因或影响其活性的其他基因上发生的遗传变化是否确实导致了混合不相容性。这种方法可能会提供对这些物种和其他物种中杂种不兼容的基因身份的主要见解。拟议研究的结果将引起生物学家的普遍兴趣，并将允许我们培训学生有关功能基因组学和进化遗传学的学生。我们完全致力于将来自代表性不足群体的个人整合到我们的研究计划中。最后，果蝇中假定的杂交男性无菌基因的鉴定可能导致发现类似的基因也涉及人类男性不育，因此拟议的研究的健康影响可能很大。