Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome

Several recent studies have estimated that a large fraction of amino acid divergence between species of Drosophila was fixed by positive selection, using statistical approaches based on the McDonald-Kreitman test. However, little is known about associated selection coefficients of beneficial amino acid mutations. Recurrent selective sweeps associated with adaptive substitutions should leave a characteristic signature in genome variability data that contains information about the frequency and strength of selection. Here, I document a significant negative correlation between the level and the frequency of synonymous site polymorphism and the rate of protein evolution in highly recombining regions of the X chromosome of D. melanogaster. This pattern is predicted by recurrent adaptive protein evolution and suggests that adaptation is an important determinant of patterns of neutral variation genome-wide. Using a maximum likelihood approach, I estimate the product of the rate and strength of selection under a recurrent genetic hitchhiking model, (lambda) over bar 2N(e)s similar to 3 x 10(-8). Using an approach based on the McDonald-Kreitman test, I estimate that similar to 50% of divergent amino acids were driven to fixation by positive selection, implying that beneficial amino acid substitutions are of weak effect on average, on the order of 10(-5) ( i.e., 2N(e)s similar to 40). Two implications of these results are that most adaptive substitutions will be difficult to detect in genome scans of selection and that population size ( and genetic drift) may be an important determinant of the evolutionary dynamics of protein adaptation.