The evolution of bacterial gene expression: integrating new functions into complex biology

细菌表现出非凡的适应和进化能力。细菌进化新特征的主要方式是水平获取编码潜在有益功能的外来DNA。然而，为了使生物体受益，获得的基因必须在适当的水平和适当的情况下表达。尽管人们对细菌的调节机制知之甚多，但对这些系统如何进化以适应新的基因和功能的了解要少得多。我的研究计划的首要目标是描述使新的遗传物质能够整合到细菌调控网络中的进化和调控过程。为了探索这一主题，我们以肠道沙门氏菌(S.enterica)作为模型系统。肠炎沙门氏菌由2000多个血清学变种(血清型)组成，这些变种在其生态位和表现出的行为方面非常不同。这里描述的短期目标使用比较基因组学方法来探索水平获得的基因和调控网络的调控进化，这些基因和调控网络在产生这种多样性方面发挥了重要作用。这些目标解决了我的研究计划总体目标的关键方面，并为未来的研究提供了一个框架，该框架将建立在这些结果的基础上，以提供对这一主题的更全面的理解。短期目标：目标1：分析水平获得的基因整合到祖先调控回路中的进化路径。这个目的是利用发现密切相关的同源基因，这些基因以不同的方式受到调控，以探索基因如何进化出新的调控联系。目的2：比较功能相似的水平获得性遗传因子的调控进化。这个目的是比较一个物种的不同成员独立获得的功能相似的基因是如何整合到他们的调控网络中的。目标3：确定水平获得的基因的主要调节因子的进化适应。特定的主控调节器经常控制大量水平获得的基因的表达。这个目的是探索这些系统的属性是如何随着进化时间的推移而改变的，以适应它们所调控的基因的生物学。影响：这项研究计划将阐明细菌如何获得新特征的一个核心但鲜为人知的方面。它有望为我们理解原核生物的进化和基因调控做出重要贡献，并在合成生物学领域有直接的应用。除了对科学的贡献外，本研究的一个重要目标是为HQP提供一流的培训机会。这项研究计划旨在建立一个非常可取的技能集，为HQP在广泛学科的职业生涯做准备。

Bacteria exhibit a remarkable ability to adapt and evolve. A primary means by which bacteria evolve new traits is through horizontally acquiring foreign DNA that encodes a potentially beneficial function. However, in order to benefit the organism, the acquired genes must be expressed at suitable levels and in appropriate situations. Although a great deal is known about bacterial regulatory mechanisms, far less is known about how these systems evolve to accommodate new genes and functions. The overarching goal of my research program is to characterize the evolutionary and regulatory processes that enable new genetic material to be integrated into bacterial regulatory networks. To explore this topic, we use the bacterial species Salmonella enterica (S. enterica) as a model system. S. enterica is comprised of more than 2000 serological variants (serovars) that are remarkably diverse with respect to their ecological niche and the behaviors they exhibit. The short-term aims described here use a comparative genomic approach to explore the regulatory evolution of horizontally-acquired genes and regulatory networks that have played important roles in generating this diversity. These aims address key aspects of the overarching goal of my research program and provide a framework for future studies that will build on these results to provide a more comprehensive understanding of this subject. Short-term goals: Aim 1: Analyze the evolutionary path by which a horizontally-acquired gene was integrated into an ancestral regulatory circuit. This aim exploits the discovery of closely-related homologous genes that are regulated in a different manner to explore how a gene can evolve new regulatory connections. Aim 2: Compare the regulatory evolution of functionally similar horizontally-acquired genetic factors. This aim compares how functionally-similar genes that are independently acquired by different members of a species are integrated into their regulatory networks. Aim 3: Define the evolutionary adaptations of a master regulator of horizontally-acquired genes. Particular master regulators often control the expression of large numbers of horizontally-acquired genes. This aim explores how the properties of these systems are altered over evolutionary time in order to accommodate the biology of genes they come to regulate. Impact: This research program will shed light on a central but poorly-understood aspect of how bacteria acquire new traits. It promises to make important contributions to our understanding of prokaryotic evolution and gene regulation and has direct applications for the field of synthetic biology. In addition to its contribution to science, an important goal of this research is to provide a first-rate training opportunity for HQP. This research program is designed to build a highly-desirable skillset to prepare HQP for careers in a wide range of disciplines.