Genetic differences among individuals reflect the combined effects of mutation, recombination, population history and natural selection. As a result, studies of natural variation can provide important insights into evolutionary and genetic mechanisms: as examples, DNA sequence conservation among distantly related species can help identify functional roles too subtle to be detected in lab settings, while analyses of population variation allow for inferences about events that are too infrequent to be measured directly. Our research employs this general approach to learn about the dynamics of adaptation and the determinants of recombination and mutation, in humans and in other species.