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的过程，以补偿先前获得的突变的有害影响。利用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Caelobditis elegans的生物学知识，对复杂动物补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将鉴定和表征一组独立进化的C.突变是最不被充分理解的进化过程，这是由于难以研究其个体和群体水平的影响。 然而，最近的技术进步，使在回答突变生物学和测试适应性进化理论的预测突出的问题的进展。补偿突变能够减轻有害突变的破坏性影响，这使得它成为病原体和生殖隔离机制快速进化的重要驱动力。这些有益的突变也可能提供一个逃生路线的有机体经历低适应性作为一个长期的小人口规模的结果。 这项工作将大大提高我们的模式和补偿性进化的遗传功能基础的理解，并揭示这种重要的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.