The combination of experimental evolution and next-generation sequencing, termed E&R, has emerged as a powerful tool for parsing the genetic foundations of adaptation. Rapid progress has been made in the genomic analysis of adaptation in asexual microbial populations. Such adaptation chiefly features “selective sweeps” in which new advantageous mutations arise at low frequency and proceed to fixation. If this is representative of adaptation in outbreeding sexual populations, then we can understand the genetic basis of long-term adaptation using microbial findings alone. However, results from early Drosophila E&R studies have failed to support this notion; instead adaptation appears to be primarily fueled by standing genetic variation. But since these studies were limited in duration, little is known about the long-term dynamics of experimental evolution in Drosophila. My work addresses this issue by comparing patterns of genomic variation and differentiation in the dozens of experimentally evolved populations D. melanogaster maintained in the Rose Lab at UC, Irvine. This experimental radiation dates back to the 1970s, and features groups of replicate populations that have been subjected to various selection regimes for dozens to hundreds of generations. Using a group of populations maintained on a laboratory domestication regime for ~1000 generations, I find that adaptation in sexual E&R is indeed characterized by a lack of fixation and populations actually harbor more genetic variation than conventional population genetic theory predicts (Chapter 1). Work comparing newly-derived and long-standing populations subjected to the same selections pressures led me to conclude that adaptation can be fast and highly repeatable at the level of genotypes and phenotypes due to standing genetic variation, and it is not dependent on the appearance beneficial de novo mutation (Chapter 2). Studying populations that were previously subjected to intense selection for desiccation resistance and their controls led me to conclude that evolutionary history does not have major long-lasting impacts in Drosophila E&R studies (Chapter 3). Lastly, using findings from two starvation-selection experiments performed at different population sizes, I show that population size is an important experimental parameter to maximize in studies aimed at deciphering the genetic architecture of complex phenotypes (Chapter 4).

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