Inferring the role of epistasis in molecular evolution
Abstract
The rules of evolution are simple: mutations introduce variants into a population, whose frequencies then change by genetic drift and natural selection. Yet these simple rules have produced remarkably complex biological structures, from the molecular scale of individual proteins to the macroscopic phenotypes in higher eukaryotes. Biological complexity often occurs because the effects of a mutation at one genetic site depend on the status of other sites in the same gene or genome Ð a phenomenon known as epistasis. As in mathematics and physics, where non-additivity produces complex behavior, so too in biology: epistatic interactions are the source of many unintuitive outcomes and complex phenotypes. This project will develop and apply methods to systematically infer the epistatic interactions that shape the evolution of biological form at three scales: 1. the stability and function of individual proteins 2. the reproductive capacity of microorganisms 3. the genetic architectures of quantitative traits in eukaryotes In all three domains researchers will develop statistical methods to infer epistasis from empirical data, as well as mathematical models to understand these inferences in terms of underlying biophysical, metabolic, or developmental processes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 14, 2019
- Source ID
- W911NF1710083
Entities
People
- Joshua B. Plotkin
Organizations
- Army Contracting Command
- United States Army
- University of Pennsylvania