Descripción del proyecto
Evaluación de la teoría de los paisajes adaptativos
Los procesos de adaptación humana a entornos nuevos representan un reto importante para la biología evolutiva. Durante décadas se ha puesto en tela de juicio el papel de la epistasia, que es el fenómeno del efecto genético de fondo sobre las mutaciones, así como un factor fundamental en la adaptación. Para abordar esta cuestión se ha utilizado el concepto de paisaje adaptativo, que representa la relación entre los genotipos y el éxito reproductivo. En la actualidad es posible evaluar esta teoría. El proyecto financiado con fondos europeos FIT2GO desarrollará la teoría de los paisajes adaptativos con la finalidad de cuantificar la epistasia a través de entornos y estructuras biológicos, además de estudiar su papel en la genética poblacional de la adaptación y la hibridización. Se espera que los hallazgos revelen el potencial para predecir métodos de resistencia frente a los patógenos.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
3012 Bern
Suiza