Natural variation in Drosophila shows weak pleiotropic effects

Pleiotropy is the phenomenon that a gene affects multiple phenotypes. The extent of pleiotropy is still disputed, mainly because of power issues. A further challenge is that empirical tests of pleiotropy are restricted to a small subset of all possible phenotypes. To overcome these limitations, we propose a new measurement of pleiotropy, which integrates across many phenotypes and multiple generations to improve power. We infer pleiotropy from the fitness cost imposed by frequency changes of pleiotropic loci. Mixing Drosophila simulans populations, which adapted independently to the same new environment using different sets of genes we show that the adaptive frequency changes have been accompanied by measurable fitness costs. Unlike previous studies characterizing the molecular basis of pleiotropy, we show that many loci, each with weak effects, contribute to genome-wide pleiotropy. We propose that the costs of pleiotropy were reduced by the modular architecture of gene expression, which facilitated adaptive gene expression changes with low impact on other functions.