The genetics of gamete sex control in convergent Caenorhabditis hermaphrodites

描述（由申请人提供）：为了实现对自然发生的遗传变化如何产生多样性的全面理解的长期目标，需要对许多分类群进行比较研究，这些分类群是由于发育遗传途径的种间差异而获得的可处理的发育性状。由于调控发育性状的许多遗传途径是广泛保守的，因此易变性状是研究的理想性状。令人惊讶的是，性别决定途径可以迅速进化，尽管这些途径在指导生物体发育为雄性或雌性方面发挥了基本作用，这种选择具有许多发育后果。即使是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（Caenorhabditis elegans）和秀丽隐杆线虫（C. briggsae）都有一条保守的性别决定途径调节性发育，但该途径的不同遗传改变在这两个物种中独立产生了相同的性发育特征——雌雄同体。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），从而导致个体自我生育。观察到，在隐杆线虫中，自我生育能力独立进化了两次，再加上在隐杆线虫中有大量的实验发育和遗传方法资源，使得雌雄同体成为一个理想的模型性状，可以对发育变化背后的进化遗传结构进行彻底的遗传分析。为了实现这一目标，拟议研究的一个实验方法是确定一个已知的雌雄同体所必需的基因，fog-2，当作为转基因转移到真正的雌性体内时，是否足以产生自我生育能力。此外，第二个基因gld-1（已知在秀丽隐杆线虫中促进精子，而在长尾隐杆线虫中促进卵子）是否在雌雄同体进化之前参与配子性别决定，将通过使用RNA干扰消除多种隐杆线虫属物种的gld-1功能并视觉评估由此产生的种系表型来确定。总之，这些方法将揭示秀丽隐杆线虫和秀丽隐杆线虫是否需要一个或多个进化变化来产生雌雄同体。预计在briggsae中还存在其他雌雄同体所需的基因，将通过对自不育蠕虫的诱变筛选来鉴定控制briggsae配子性命运的新基因。描述秀丽隐杆线虫和秀丽隐杆线虫独立获得雌雄同体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，发现调节生殖细胞性命运的新遗传因素可能会提高我们对人类雌雄同体和不孕症原因的理解。

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.