Evolve and Resequence: Bodysize

Genome-wide association studies hold the promise of comprehensively identifying the genetic basis of natural trait variation. By quantifying how genetic polymorphisms induce large, small, precise, general, or conditional effects on traits, we can unlock a vast reservoir of natural variation for use in understanding how biological systems function and evolve. However, the sample sizes needed to identify variants with low population frequencies or modest effects may be prohibitive in most cases. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to map hundreds of loci which harbor natural variation affecting body size in Drosophila melanogaster. At some loci, mapping resolution of less than 100-bp allows precise hypotheses to be formed regarding causal polymorphisms, while other regions are large and contain many genes. In these regions, follow-up studies using the set of significantly evolved polymorphisms should be highly productive. By resequencing experimentally evolved populations, we have addressed long-standing questions regarding the nature of quantitative genetic variation, the effect of selection on the genome, and have mapped specific polymorphisms affecting a model trait. For species with a suitable life history, this “Evolve and Resequence” approach may frequently be the most efficient and comprehensive way to link genotype and phenotype, and we expect it to be a major component of future efforts to do so.