Evolution of Developmental Regulatory Pathways

基因组测序的出现使进化论研究重新回到了 生物医学研究，因为它们对于解释信息是如何 模式生物中的调控途径可能适用于人类。最大的之一 该领域的问题是，这些监管途径是如何演变的。 三个因素使线虫成为研究进化的极佳模型 流程。首先，线虫是生殖生物学研究的一个主要焦点，细胞 死亡、微小核糖核酸、衰老和其他医生感兴趣的话题。第二， 可用于处理这些动物的基因组和功能工具非常出色。 第三，优良性状可供研究。例如，两性人 线虫、线虫和线虫的发育是独立进化的。 这项建议描述了使用基因和分子技术来 了解布里奇萨斯的两性发育是如何进化的。既然是两性人 线虫调节性别决定途径，使XX动物能够 精子，这一特征是研究调控途径在进化过程中如何变化的理想选择。 到目前为止，我们已经鉴定并克隆了导致XX动物发育为AS的GLF-1。 两性基因，以及作用于GLF-1下游的GLF-2。这些基因都是C。 Briggsae，对了解两性人发育的起源至关重要。 这个项目有三个具体目标。第一个是筛选与之相互作用的蛋白质。 GLF-1。由于GLF-1是一类新的F-box蛋白的成员，它的结合伙伴是 理解它是如何控制发展的关键。第二个目标是克隆和 一种新的性别决定基因GLF-2的特征 促进精子发生。第三个目的是使用增强剂和抑制剂。 筛选以确定在这一途径中起作用的其他基因，并对这些基因进行表征 基因。这些基因将成为未来克隆和分子分析的候选基因。许多基因相互协作，调节人类的发育和抗击疾病的方式。世界上大部分的 由美国国立卫生研究院资助的基础研究通过研究这些基因来关注它们是如何工作的。 在简单的生物中。这个项目将阐明基因的功能是如何变化的。 在进化期间，这可以帮助科学家选择研究哪些生物，以及 避免对它们的医学意义做出错误的推断。

The advent of genome sequencing restored evolutionary studies to a central place in biomedical research, since they are essential for interpretting how information about regulatory pathways in model organisms might apply to humans. One of the big questions in the field is how these regulatory pathways evolve. Three factors make nematodes an excellent model for studying evolutionary processes. First, C. elegans is a major focus of study about reproductive biology, cell death, micro-RNAs, aging, and other subjects of interest to physicians. Second, the genomic and functional tools available for working with these animals are outstanding. Third, excellent traits are available for study. For example, hermaphrodite development evolved independently in the nematodes C. elegans and C. briggsae. This proposal describes experiments that use genetic and molecular techniques to learn how hermaphroditic development evolved in C. briggsae. Since hermaphrodite nematodes modulate the sex-determination pathway to allow XX animals to make sperm, this trait is ideal for learning how regulatory pathways change during evolution. So far, we have identified and cloned glf-1, which causes XX animals to develop as hermaphrodites, and glf-2, which acts downstream of glf-1. These genes are novel to C. briggsae, and critical to learning how hermaphrodite development originated. This project has three specific aims. The first is to screen for proteins that interact with GLF-1. Since GLF-1 is a member of a new class F-box proteins, its binding partners are the key to understanding how it controls development. The second aim is to clone and characterize glf-2, a new sex-determination gene that acts downstream of glf-1 to promote spermatogenesis. The third aim involves the use of enhancer and suppressor screens to identify additional genes that act in this pathway, and to characterize these genes. These genes would be candidates for future cloning and molecular analyses. Many genes cooperate to regulate how humans develop and fight disease. Much of the basic research funded by the NIH focuses on how these genes work by studying them in simple creatures. This project will elucidate how the functions of genes change during evolution, which could help scientists choose which creatures to study, and avoid mistaken inferences about their medical significance.