Gene duplication and divergence: the bigger picture

基因复制和分歧：大局观

基本信息

批准号：
10222726
负责人：
SHELLEY D. COPLEY
金额：
$ 34.9万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-12 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222726
关键词：
Address Affect Alleles Arginine Bacteria Biochemical Bioinformatics Biological Biological Models Carbon Complex Enzymes Escherichia coli Evolution Exposure to Family member Firmicutes Gammaproteobacteria Gene Duplication Genes Genetic Genetic Transcription Genome Genomics Glucose Growth Investigation Lactobacillus casei Lead Life Link Metabolic Metabolism Microbe Modeling Mutation Organism Orthologous Gene Pesticides Pharmacologic Substance Phase Physiological Play Point Mutation Process Processed Genes Proline Proteins Reaction Rest Role Salmonella enterica Shapes Side Signaling Molecule Source Stimulus System Vibrio fischeri Work anthropogenesis detection of nutrient environmental change experimental study fitness improved innovation insight life history microbial genome neglect novel paralogous gene pressure repaired side effect single molecule whole genome

Address Affect Alleles Arginine Bacteria Biochemical Bioinformatics Biological Biological Models Carbon Complex Enzymes Escherichia coli Evolution Exposure to Family member Firmicutes Gammaproteobacteria Gene Duplication Genes Genetic Genetic Transcription Genome Genomics Glucose Growth Investigation Lactobacillus casei Lead Life Link Metabolic Metabolism Microbe Modeling Mutation Organism Orthologous Gene Pesticides Pharmacologic Substance Phase Physiological Play Point Mutation Process Processed Genes Proline Proteins Reaction Rest Role Salmonella enterica Shapes Side Signaling Molecule Source Stimulus System Vibrio fischeri Work anthropogenesis detection of nutrient environmental change experimental study fitness improved innovation insight life history microbial genome neglect novel paralogous gene pressure repaired side effect single molecule whole genome

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项目摘要

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.

基因的重复和差异驱动了生活的所有领域的进化创新。我们学到了从以前的生物信息学，遗传和生化研究中进行了很大的重点，该研究的重点是重复的基因。但是，这些方法错过了一个重要的生物学现实 - 新近的背景重复的基因正在发展。基因组中其他地方的突变，可以改善面对适应性进化挑战可能与经历差异的基因突变一样重要。突变可能会以短期内提高健身的方式重新代谢或监管网络，但可以在此过程中牺牲先前发展良好的功能。我们称这些“权宜”突变。重复基因中的突变和突变是随着生物进化新基因而密不可分的。我们将使用模型系统调查新蛋白进化过程中权宜突变的作用其中需要这种新颖的蛋白质才能生长。 Δargc大肠无法合成精氨酸。点突变允许E383a ProA（ProA*）催化其天然反应和ARGC反应，尽管很差。我们进化了 Δargcproa*大肠杆菌在葡萄糖 +脯氨酸上（仅选择精氨酸的条件合成）。通过扩增PROA*可以提高增长率，该突变提高了ProA*的能力催化ARGC反应以及方便突变，从而增强其他人精氨酸的合成机制。我们将使用我们的∆argc proa*模型系统来解决基因复制的三个方面分歧肯定在扩展生物的能力方面发挥了重要作用基因组，并确定哪些谱系获胜以及在环境条件发生变化时损失哪些。在AIM 1中，我们将确定在∆argc Proa*菌株演化期间出现的方便突变在有效替换ARGC之后，在葡萄糖 +脯氨酸上是有害的，以及它们如何成为修理。在AIM 2中，我们将研究方便突变如何在更复杂的情况下增强健身当需要ProA*的原始功能和新颖功能时。最后，在AIM 3中，我们将解决基因组直系同源物之间的含量，基因含量和序列差异会影响a的进化过程在四种不同细菌中替代ARGC。这项工作将回答有关新基因如何在整个生命史上发展的重要问题在目前，由于人为药物和农药施加的新选择压力。我们将更好地了解编码弱链接的新基因中突变之间的相互作用基因组的其余部分中的酶和突变。我们将确定造成了哪种侧支损害通过权宜之计的突变以及这些权宜之计的突变本身如何容纳。最后，我们会的了解微生物基因组的差异如何影响新酶进化的潜力面临相同进化挑战的不同细菌。