DISSERTATION RESEARCH: Gene Regulation Evolution and Speciation in House Mice

本项目将利用家鼠（Mus musculus）模型系统进行受控实验室实验，以了解基因调控在物种形成中的作用。物种形成研究的一个主要目标是揭示物种之间的遗传差异，这些差异是生殖隔离的基础。虽然这一领域的大部分工作都集中在确定有助于物种之间生殖隔离的特定基因上，但基因调控可能在这一过程中发挥重要作用。尽管如此，很少有系统的尝试将调节进化与生殖隔离联系起来。表征家鼠亚种之间的调控进化将提供新的见解调控网络如何演变和分歧，这对我们理解复杂表型的进化以及物种形成过程具有广泛的意义。此外，研究人员将与来自代表性不足的群体的本科生进行研究，并为该项目提供公共和K12外展服务。利用家鼠亚种之间的杂交，其中杂交功能障碍在很大程度上是单向的，拟议的工作将使用各种基因组方法（即，芯片测序、mRNA测序和核糖体分析）来表征与杂种不育性相关的转录和翻译水平上的基因调控的变化。本论文主要研究以下几个问题：1）不同水平的基因调控对物种分化的作用是什么？2）调控分歧在物种间生殖隔离中的作用是什么？本文概述的工作将是第一个：1）表征哺乳动物物种之间翻译效率的差异，2）在转录和翻译水平上研究杂种不育与基因调控之间的关系。

This project will make use of controlled laboratory experiments utilizing the model system of house mice (Mus musculus) to understand the role of gene regulation in speciation. A primary goal of speciation research is to uncover the genetic differences between species that underlie reproductive isolation. While much of the work in this field has focused on identifying specific genes that contribute to reproductive isolation between species, gene regulation may play a large role in this process. Despite this, there are been few systematic attempts to link regulatory evolution to reproductive isolation. Characterizing regulatory evolution between house mouse subspecies will provide novel insight into how regulatory networks evolve and diverge which has broad implications for our understanding of the evolution of complex phenotypes as well as the speciation process. In addition, the investigators will engage in research with undergraduates from underrepresented groups and provide public and K12 outreach on this project.Taking advantage of a cross between house mouse subspecies, where hybrid dysfunction is largely unidirectional, the proposed work will use a variety of genomic methods (i.e., ChiP-sequencing, mRNA-sequencing, and ribosome profiling) to characterize changes in gene regulation on the transcriptional and translational level that are associated with hybrid sterility. This dissertation work will address the following questions: 1) What is the role of different levels of gene regulation to species divergence? and 2) What is the role of regulatory divergence in reproductive isolation between species? The work outlined here will be the first to: 1) characterize divergence in translational efficiency between mammalian species, and 2) examine the relationship between hybrid sterility and gene regulation on the transcriptional and translational level.