Evolutionary Paths of Compensatory Mutations in Genetic Networks

补偿性适应是自然选择倾向于基因突变来补偿先前获得的突变的有害影响的过程。利用实验实验室进化和尖端的全基因组分子技术，Estes和Denver将利用模型线虫秀丽隐杆线虫（Caenorhabditis elegans）的良好生物学特性，对复杂动物的代偿适应的遗传和功能基础进行首次深入研究。具体来说，Estes和Denver将在一组独立进化的秀丽隐杆线虫种群中识别和描述负责代偿进化的突变的功能和适合度效应。突变是最不容易理解的进化过程，因为很难研究其个体和群体水平的影响。然而，最近的技术进步使得在回答突变生物学中悬而未决的问题和测试适应性进化理论的预测方面取得了进展。改善有害突变的破坏性影响的能力使补偿性突变成为病原体快速进化和生殖隔离机制的重要驱动力。这些有益的突变也可能为由于长期小种群规模而经历低适应性的生物体提供了一条逃生途径。这项工作将大大提高我们对代偿进化的模式和遗传功能基础的理解，并揭示这种重要适应形式的一般特征。

Compensatory adaptation is the process whereby natural selection favors genetic mutations that compensate for the harmful effects of previously acquired mutations. Using experimental laboratory evolution and cutting-edge, whole-genome molecular techniques, Estes and Denver will take advantage of the well-understood biology of the model nematode, Caenorhabditis elegans, to perform the first in-depth study of the genetic and functional bases of compensatory adaptation in a complex animal. Specifically, Estes and Denver will identify and characterize the functions and fitness effects of mutations responsible for compensatory evolution in a set of independently evolved populations of C. elegans.Mutation is the least well-understood evolutionary process, due to the difficulty in studying both its individual and its population-level effects. Recent technological advances, however, enable progress in answering outstanding questions in mutation biology and testing predictions of adaptive evolutionary theory. The ability to ameliorate the damaging impacts of deleterious mutations makes compensatory mutation an important driving force in the rapid evolution of pathogens and of reproductive isolating mechanisms. These beneficial mutations may also offer an escape route to organisms experiencing low fitness as a result of prolonged small population size. This work will greatly improve our understanding of the patterns and genetic functional bases of compensatory evolution and reveal general features of this important form of adaptation.