Genetic mechanisms and evolutionary processes underlying diversity within and between species

 描述(由申请者提供)：该项目的长期目标是了解在物种内和物种之间产生表型多样性的遗传机制和进化过程。这包括发现导致表型差异的基因，确定这些基因中的哪些变化影响表型，以及确定这些变化如何改变分子、细胞和发育过程。它还包括弄清楚突变和选择是如何共同作用产生这些变化的。这些目标将通过结合发育生物学、种群和数量遗传学、分子进化、生物信息学和基因组学的方法来研究果蝇(果蝇)和酵母(酵母菌)来实现。提出的具体实验旨在解决以下四个互补问题：(1)表型差异背后的遗传和分子机制是什么？它们是如何进化的？(2)顺式调控序列如何决定基因表达，它们的结构如何随着时间的推移而变化？(3)由顺式和反式作用因子组成的调控网络如何进化并解释基因表达的变化？以及(4)新的调控突变的功能特性是什么，它们如何影响调控变异？综上所述，这项工作将促进我们对基因-表型图谱以及它们在物种内和物种之间如何变化的理解。这项工作将特别强调影响基因表达调控的遗传变化，这是将基因类型转化为表型的关键步骤。最终，从这些研究中吸取的经验教训将有助于预测和解释与人类健康相关的基因和表型变异模式的一般框架。

 DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the genetic mechanisms and evolutionary processes responsible for generating phenotypic diversity within and between species. This includes discovering the genes responsible for phenotypic divergence, identifying which changes within these genes affect the phenotype, and determining how these changes alter molecular, cellular, and developmental processes. It also includes figuring out how mutation and selection have worked together to give rise to these changes. These goals will be accomplished by combining methods from developmental biology, population and quantitative genetics, molecular evolution, bioinformatics and genomics to study both fruit flies (Drosophila) and yeast (Saccharomyces). Specific experiments proposed are designed to address the following four complementary questions: (1) What are the genetic and molecular mechanisms underlying phenotypic differences and how did they evolve? (2) How do cis-regulatory sequences determine gene expression and how does their architecture change over time? (3) How do regulatory networks composed of cis- and trans-acting factors evolve and account for changes in gene expression? and (4) What are the functional properties of new regulatory mutations and how do they influence regulatory variation? Taken together, this work will advance our understanding of genotype-phenotype maps and how they vary within and between species. Genetic changes affecting the regulation of gene expression, an essential step in translating genotypes into phenotypes, will be given particular emphasis in this work. Ultimately, lessons learned from these studies will contribute to a general framework for predicting and interpreting patterns of genotypic and phenotypic variation related to health in human populations.