The genetics of gamete sex control in convergent Caenorhabditis hermaphrodites

描述(申请人提供)：要实现对自然发生的遗传变化如何产生多样性的全面理解这一长期目标，将需要对由于发育遗传途径的物种间差异而获得的许多易处理的发育特征进行比较研究。因为许多调节发育性状的遗传途径是广泛保守的，所以容易发生变化的性状是理想的研究性状。令人惊讶的是，性别决定途径可以快速进化，尽管这些途径在指导有机体发育为雄性或雌性方面发挥着基础性作用，这一选择具有许多发育后果。即使是亲缘关系密切的物种之间性别决定途径的变化也会产生显著的发育差异。秀丽隐杆线虫和桥隐杆线虫中保守的性别决定途径调节性发育，但该途径的不同基因改变独立地在这两个物种中产生了相同的性发育特征-两性。这些基因修饰导致雌性在产生雌性配子(卵子)之前产生雄性配子(精子)，从而导致个体自我繁殖。观察到，线虫的自我生育能力独立进化了两次，再加上线虫的实验发育和遗传方法可利用的大量资源，使两性行为成为对潜在发育变化的进化遗传结构进行彻底遗传分析的理想模式性状。为了实现这一目标，这项拟议研究的一个实验方法是确定已知的两性生殖所必需的基因FOG-2在作为转基因进入真正的雌性体内时是否足以产生自我生育能力。此外，第二个基因GLD-1在秀丽线虫中促进精子，但在桥线虫中促进卵子，在两性进化之前是否参与配子性别决定，将通过使用RNA干扰消除线虫属多个物种的GLD-1功能并从视觉上评估由此产生的种系表型来确定。总而言之，这些方法将揭示线虫和桥线虫是否需要一个或多个进化变化才能产生两性现象。由于预期在布里奇萨斯虫中还存在雌雄同体所必需的额外基因，因此将通过对自育蠕虫的诱变筛选来鉴定控制布里奇萨斯虫配子体有性命运的新基因。描述导致线虫和桥线虫雌雄同体独立获得的一系列遗传变化将有助于理解遗传途径如何进化以产生发育变化的长期目标。此外，识别调节生殖细胞性命运的新的遗传因素可能会提高我们对人类两性畸形和不育原因的理解。

DESCRIPTION (provided by applicant): Achieving the long-term goal of formulating a comprehensive understanding of how naturally-occurring genetic changes produce diversity will require the comparative study in many taxa of tractable developmental traits that were acquired as a result of inter-species divergence in developmental genetic pathways. Because many genetic pathways regulating developmental traits are broadly conserved, traits prone to change are ideal traits to study. Surprisingly, sex determination pathways can evolve rapidly, despite the fundamental role of these pathways in instructing an organism to develop as a male or female, a choice having numerous developmental consequences. Changes in sex determination pathways between even closely related species can produce striking developmental differences. A conserved sex determination pathway in Caenorhabditis elegans and C. briggsae regulates sexual development, but different genetic alterations of the pathway independently produced the same sexual developmental trait, hermaphroditism, in both species. These genetic modifications cause females to produce male gametes (sperm) prior to producing female gametes (eggs), resulting in individual self-fertility. The observation that self-fertility independently evolved twice in Caenorhabditis, coupled with the vast resources available for experimental developmental and genetic approaches in Caenorhabditis, makes hermaphroditism an ideal model trait with which to conduct a thorough genetic analysis of the evolutionary genetic architecture underlying developmental change. In order to achieve this objective, one experimental approach of the proposed research is to determine whether a gene known to be necessary for hermaphroditism, fog-2, is sufficient to produce self-fertility when moved as a transgene into true females. In addition, whether a second gene, gld-1, known to be sperm- promoting in C. elegans but egg-promoting in C. briggsae, was involved in gamete sex determination prior to the evolution of hermaphroditism will be identified by eliminating gld-1 function in multiple species of the genus Caenorhabditis using RNA interference and visually assessing resulting germline phenotypes. Together, these approaches will reveal whether one or multiple evolutionary changes were required in C. elegans and C. briggsae to produce hermaphroditism. In anticipation that additional genes necessary for hermaphroditism exist in C. briggsae, novel genes controlling gamete sexual fate in C. briggsae will be identified using a mutagenesis screen for self-sterile worms. Describing the suites of genetic changes responsible for the independent acquisition of hermaphroditism in C. elegans and C. briggsae will contribute to the long-term goal of understanding how genetic pathways evolve to produce developmental change. Additionally, identifying novel genetic factors regulating germ cell sexual fate might improve our understanding of causes of human hermaphroditism and infertility.