The molecular basis of speciation in Drosophila

 描述（由申请人提供）： 理解杂种不育和杂种不活力的分子基础是物种形成的一个基本问题，一个物种分裂成两个物种的过程。研究杂交功能障碍还提供了一种独特的途径来识别基因，尽管这些基因在重要的细胞过程中发挥作用，但在物种之间迅速进化。我们的目标是利用高度多学科的方法来了解果蝇物种形成的遗传和分子基础。特别是，我的实验室有兴趣解决以下问题：第一，是什么基因的基础上的不育和不育的果蝇物种之间的杂交？第二，在杂交体中被破坏的分子过程是什么？第三，是什么样的生物力量推动了导致杂交功能障碍的基因的快速进化？ 随着新一代测序、基因工程和细胞生物学方法的最新技术进步，现在有可能解决物种形成的分子基础等基本问题。首先，我的实验室设计了一种新的基于基因组学的方法来有效地识别杂种不育和杂种不育基因。我们利用这种新的方法，成功地确定了一个新的杂交不亲和基因，这是必不可少的介导杂种雄性不育D。melanogaster和D.模拟。我们正在研究这种基因在细胞对DNA损伤的反应中的作用，这一过程在癌症生物学中至关重要。 其次，我们进行实验来了解Overdrive的功能，我们发现了一个基因，它在波哥大和美国亚种D.伪暗我的实验室正在利用遗传学和细胞生物学的方法来了解超速驱动在减数分裂染色体分离中的作用。我们正在开发新的工具，以了解生殖系中的发育机制，这些发育机制对减数分裂期间染色体分离的错误做出反应，这一过程对出生缺陷的原因具有根本性的影响。这一系列的工作也提供了深入了解分离扭曲的分子机制。 最后，我们正在使用我们的新方法来识别与Overdrive相互作用的基因，这些基因会导致波哥大和美国果蝇亚种之间的杂交不育和分离畸变。这代表了一个重要的一步，在获得一个完整的图片的基因和分子过程中，是重要的物种形成的最早阶段，并提供了一个前所未有的机会，检查分离扭曲的作用，作为一个驱动力的杂交不育的进化。总之，这些实验将建立D. pseudobscura是遗传、分子和进化水平上物种形成的最佳理解案例之一。

 DESCRIPTION (provided by applicant): Understanding the molecular basis of hybrid sterility and hybrid inviability is a fundamental problem in speciation, the process by which one species splits into two. Studying hybrid dysfunction also provides a unique route to identifying genes that, despite functioning in essential cellular processes, evolve rapidly between species. Our goal is to understand the genetic and molecular bases of speciation in Drosophila using a highly multidisciplinary approach. In particular, my laboratory is interested in addressing the following questions: First, what are genes that underlie the sterility and inviability in hybrids between Drosophila species? Second, what are the molecular processes that are disrupted in hybrids? Third, what are the biological forces that drive the rapid evolution of genes that cause hybrid dysfunction? With recent technological advances in next-generation sequencing, genetic engineering, and cell biological approaches, it is now possible to address fundamental questions shrouding the molecular basis of speciation. First, my laboratory has designed a new genomics-based approach to efficiently identify hybrid sterility and hybrid inviability genes. We used this novel approach to successfully identify a new hybrid incompatibility gene, which is essential for mediating hybrid male inviability between D. melanogaster and D. simulans. We are studying the role of this gene in the cellular response to DNA damage, a process that is of critical importance in cancer biology. Second, we performing experiments to understand the function of Overdrive, a gene that we discovered for its essential role in both segregation distortion and male sterility in hybrids between the Bogota and USA subspecies of D. pseudoobscura. My laboratory is using genetic and cell biological approaches to understand the function of Overdrive in the meiotic chromosomal segregation. We are developing new tools to understand the developmental mechanisms in the germline that respond to errors in chromosomal segregation during meiosis, a process that has fundamental implications for the causes of birth defects. This line of work is also providing insights into the molecular mechanisms of segregation distortion. Lastly, we are using our new approach to identify the genes that interact with Overdrive to cause hybrid sterility and segregation distortion in hybrids between the Bogota and USA subspecies of Drosophila pseudoobscura. This represents a major step forward in gaining a complete picture of the genes and molecular processes that are important in the earliest stages of speciation, and provides an unprecedented opportunity to examine the role of segregation distorters as a driving force in the evolution of hybrid sterility. Together, these experiments will establish the Bogota-USA subspecies of D. pseudoobscura as one of the best-understood cases in speciation at the genetic, molecular and evolutionary levels.