Evolutionary Paths of Compensatory Mutations in Genetic Networks

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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.