Abstract
Understanding the determinants of the adaptive substitution rate is a central question inmolecular evolution. In particular, the influence of the effective population size N e on positiveselection as well as the nature of amino acid changes that lead to adaptation are still debated. TheDFE-α method, which was derived from the seminal McDonald & Kreitman test, is a powerful toolfor estimating the adaptive substitution rate. However, it is sensitive to various sources of bias. Inthis thesis, we identified two major sources of bias of this test, long-term fluctuations of theselective-drift regime through demographic fluctuations, and GC-biased gene conversion (gBGC).Using simulations, we showed that under plausible scenarios of fluctuating demography, the DFE-αmethod can lead to a severe over-estimation of the adaptive substitution rate. We also showed thatpolymorphism data reflect a transient selective-drift regime which is unlikely to correspond to theaverage regime experienced by genes and genomes during the long-term divergence betweenspecies. This violates an important assumption of the DFE-α method. Our results also indicate thatgBGC leads to an over-estimation of the adaptive substitution rate in primates and birds. Using adataset of nine metazoan taxa for a total of 40 species, we started an analysis aiming at identifyingthe type of amino acid changes that are more prone to adaptation, and evaluated the link between N eand the adaptive substitution rate while accounting for the two sources of bias previously explored.We reveal for the first time a negative relationship between the adaptive substitution rate and life-history traits representative of long-term N e . This result is in contradiction with the widespreadhypothesis that adaptation is more efficient in large populations.