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。我们已经了解到 从以前的生物信息学、遗传学和生化研究中获得了大量的信息，这些研究集中在 复制的基因。然而，这些方法忽略了一个重要的生物学现实--一个新的 复制的基因正在进化。基因组中其他地方的突变可以改善面对 进化挑战可能与经历分化的基因突变一样重要。是这样的 突变可能会在短期内以提高健康的方式重新连接代谢或调节网络，但也可能 在这一过程中牺牲了以前发展良好的功能。我们称这些突变为“权宜之计”。权宜之计 随着生物体进化出新的基因，重复基因中的突变和突变不可避免地交织在一起。 我们将使用模型系统研究在新蛋白质进化过程中权宜性突变的作用。 其中新蛋白质是生长所必需的。∆argc大肠杆菌不能合成精氨酸。一种点突变 允许E383A ProA(ProA*)同时催化其天然反应和ARGC反应，尽管效果不佳。我们进化了 ∆-ArGCproA*大肠杆菌葡萄糖-脯氨酸(只能选择改良精氨酸的条件) 综合)。通过扩增ProA*来提高生长速度，ProA*是一种突变，可以提高ProA*的能力 催化ARGC反应，以及通过其他途径促进精氨酸合成的有利突变 机械装置。我们将使用我们的∆ARGC ProA*模型系统解决三个方面的基因复制和 分歧肯定在扩大有机体的能力，塑造他们的 基因组，并在环境条件变化时决定谁的血统赢了谁输了。 在目标1中，我们将确定在∆argc proA*株进化过程中产生的哪些有利突变 在ARGC的有效替代品已经进化后，葡萄糖中的Pro是有害的，以及它们是如何 修好了。在目标2中，我们将研究在更复杂的情况下，有利的突变如何增强适应性。 既需要ProA*的原始功能又需要ProA*的新功能时。最后，在目标3中，我们将解决基因组如何 同源基因之间的含量、基因背景和序列差异影响着一个基因的进化过程 在四个不同的细菌物种中替代ARGC。 这项工作将回答有关新基因如何在整个生命历史中进化的重要问题。 在目前，由于人为药物和杀虫剂施加的新的选择压力。 我们将更好地了解编码弱链的新基因突变之间的相互作用。 酶和基因组其余部分的突变。我们将确定造成何种附带损害 通过权宜性突变，以及这些权宜性突变本身是如何适应的。最后，我们会 洞察微生物基因组的差异如何影响一种新酶的进化潜力 不同的细菌面临着相同的进化挑战。

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.