Gene duplication and divergence: the bigger picture

基因复制和分化推动了生命各个领域的进化创新。我们已经学会 从以前的生物信息学，遗传学和生物化学研究中， 复制基因然而，这些方法忽略了一个重要的生物学现实--一个新的 复制基因正在进化基因组中其他地方的突变，在面对一个 进化的挑战可能和基因变异一样重要。等 突变可能会在短期内以提高适应性的方式重新连接代谢或调节网络，但也可能 在这个过程中牺牲了一个先前进化良好的功能。我们称之为“权宜”突变。权宜之计 当生物体进化出新的基因时，重复基因中的突变和突变不可避免地交织在一起。 我们将使用一个模型系统研究在新蛋白质进化过程中权宜突变的作用 其中新蛋白质是生长所必需。E.大肠杆菌不能合成精氨酸。的点突变 允许E383 A ProA（ProA*）催化其天然反应和ArgC反应，尽管很差。我们进化 A * E.大肠杆菌对葡萄糖+脯氨酸的选择（仅选择改善的精氨酸的条件 合成）。通过proA* 的扩增来提高生长速率，proA * 是一种提高ProA* 的能力的突变， 催化ArgC反应，以及增强其他人的精氨酸合成的有利突变 机制等我们将使用我们的ProargC proA* 模型系统来解决基因复制的三个方面， 分歧肯定在扩大生物体的能力方面发挥了重要作用，塑造了它们的 基因组，并决定哪些血统赢了，哪些失去了环境条件的变化。 在目标1中，我们将确定在HLAargC proA* 菌株的进化过程中出现了哪些有利的突变 对葡萄糖+脯氨酸是有害的后，ArgC的有效替代已经发展，以及他们如何可以 修复.在目标2中，我们将研究在更复杂的情况下，权宜突变如何增强适应度 当需要ProA* 的原始功能和新功能时。最后，在目标3中，我们将讨论基因组如何 直向同源物之间的基因内容、基因背景和序列差异影响了一个物种的进化过程。 在四种不同的细菌物种中替换ArgC。 这项工作将回答关于新基因在整个生命史中是如何进化的重要问题 目前，由于人为药物和农药施加的新的选择性压力， 我们将更好地了解编码弱连接的新基因中突变之间的相互作用， 酶和基因组其他部分的突变。我们会确定会造成什么样的附带损害 而这些变化，又是如何变化的呢？最后我们将 深入了解微生物基因组的差异如何影响一种新酶的进化潜力， 不同的细菌面临着同样的进化挑战。

Gene duplication and divergence has driven evolutionary innovation in all domains of life. We have learned a great deal from previous bioinformatic, genetic and biochemical investigations that focused on mutations in duplicated genes. However, these approaches miss an important biological reality – the context in which a newly duplicated gene is evolving. Mutations elsewhere in the genome that improve fitness in the face of an evolutionary challenge may be just as important as mutations in the gene undergoing divergence. Such mutations may rewire metabolic or regulatory networks in ways that boost fitness in the short run, but may sacrifice a previously well-evolved function in the process. We term these “expedient” mutations. Expedient mutations and mutations in duplicated genes are inextricably intertwined as organisms evolve new genes. We will investigate the role of expedient mutations during evolution of a new protein using a model system in which that novel protein is required for growth. ∆argC E. coli cannot synthesize arginine. A point mutation allows E383A ProA (ProA*) to catalyze both its native reaction and the ArgC reaction, albeit poorly. We evolved ∆argC proA* E. coli on glucose + proline (conditions in which there is selection only for improved arginine synthesis). Growth rate is improved by amplification of proA*, a mutation that improves the ability of ProA* to catalyze the ArgC reaction, as well as expedient mutations that enhance arginine synthesis by other mechanisms. We will use our ∆argC proA* model system to address three aspects of gene duplication and divergence certain to have played a major role in expanding the capabilities of organisms, shaping their genomes, and determining which lineages win and which lose when environmental conditions change. In Aim 1, we will determine which expedient mutations that arose during evolution of the ∆argC proA* strain on glucose + proline are detrimental after an efficient replacement for ArgC has evolved, and how they can be repaired. In Aim 2, we will investigate how expedient mutations enhance fitness in the more complex situation when both the original and novel functions of ProA* are required. Finally, in Aim 3, we will address how genome content, gene context and sequence differences between orthologs affect the process of evolution of a replacement for ArgC in four different bacterial species. This work will answer important questions about how new genes have evolved throughout the history of life and in the present due to new selective pressures imposed by anthropogenic pharmaceuticals and pesticides. We will gain a better understanding of the interplay between mutations in a new gene encoding a weak-link enzyme and mutations in the rest of the genome. We will establish what kinds of collateral damage are caused by expedient mutations, and how those expedient mutations are themselves accommodated. Finally, we will gain insight into how differences in microbial genomes affect the potential for evolution of a new enzyme in different bacteria exposed to the same evolutionary challenge.