<p>Our understanding of the genetic basis of phenotypic diversity is limited by thepaucity of examples in which multiple, interacting loci have been identified. Weshow that natural variation in the efficiency of sporulation, the program in yeast that initiates the sexual phase of the life cycle, between oak tree and vineyard strains is due to allelic variation between four nucleotide changes in three transcription factors: IME1, RME1, and RSF1. Furthermore, we identified that selection has shaped quantitative variation in yeast sporulation between strains. These results illustrate how genetic interactions between transcriptionfactors are a major source of phenotypic diversity within species.</p>