Description du projet
Évaluer la théorie du paysage adaptatif
Les processus d’adaptation de l’homme à de nouveaux environnements représentent un défi majeur pour la biologie de l’évolution. Le rôle de l’épistasie, le phénomène de l’effet du contexte génique sur les mutations et un facteur clé de l’adaptation, est contesté depuis des décennies. Le concept de paysage adaptatif qui illustre la relation entre les génotypes et le succès reproductif a été utilisé pour aborder la question. L’évaluation de cette théorie est désormais chose possible. Le projet FIT2GO, financé par l’UE, développera la théorie des paysages adaptatifs, dans le but de quantifier l’épistasie via les structures et les environnements biologiques, et d’étudier son rôle sur la génétique de l’adaptation et de l’hybridation des populations. Les résultats devraient révéler le potentiel de prédiction des méthodes de résistance aux agents pathogènes.
Objectif
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.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
3012 Bern
Suisse