Project description
Evaluating fitness landscape theory
The processes of human adaptation to new environments represent a major challenge in evolutionary biology. The role of epistasis, the phenomenon of the genetic background effect on mutations and a key factor in adaptation, has been disputed for decades. The concept of the fitness landscape that pictures the relationship between genotypes and reproductive success has been used to approach the question. Evaluation of the theory is now possible. The EU-funded FIT2GO project will develop the theory of fitness landscapes, aiming to quantify epistasis via biological structures and environments, and study its role on the population genetics of adaptation and hybridisation. The findings are expected to reveal the potential for predicting methods to resist pathogens.
Objective
A major challenge in evolutionary biology is to quantify the processes and mechanisms by which populations adapt to new environments. In particular, the role of epistasis, which is the genetic-background dependent effect of mutations, and the constraints it imposes on adaptation, has been contentious for decades. This question can be approached using the concept of a fitness landscape: a map of genotypes or phenotypes to fitness, which dictates the dynamics and the possible paths towards increased reproductive success. This analogy has inspired a large body of theoretical work, in which various models of fitness landscapes have been proposed and analysed. Only recently, novel experimental approaches and advances in sequencing technologies have provided us with large empirical fitness landscapes at impressive resolution, which call for the evaluation of the related theory.
The aim of this proposal is to build on the theory of fitness landscapes to quantify epistasis across levels of biological organization and across environments, and to study its impact on the population genetics of adaptation and hybridization. Each work package involves classical theoretical modelling, statistical inference and method development, and data analysis and interpretation; a combination of approaches for which my research group has strong expertise. In addition, we will perform experimental evolution in Escherichia coli and influenza to test hypotheses related to the change of fitness effects across environments, and to adaptation by means of highly epistatic mutations. We will specifically apply our methods to evaluate the potential for predicting routes to drug resistance in pathogens. The long-term goal lies in the development of a modeling and inference framework that utilizes fitness landscape theory to infer the ecological history of a genome, which may ultimately allow for a prediction of its future adaptive potential.
Fields of science
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Funding Scheme
ERC-STG - Starting GrantHost institution
3012 Bern
Switzerland