  In the classic view introduced by R. A. Fisher, a quantitative trait is
encoded by many loci with small, additive effects. Recent advances in QTL
mapping have begun to elucidate the genetic architectures underlying vast
numbers of phenotypes across diverse taxa, producing observations that
sometimes contrast with Fisher's blueprint. Despite these considerable
empirical efforts to map the genetic determinants of traits, it remains poorly
understood how the genetic architecture of a trait should evolve, or how it
depends on the selection pressures on the trait. Here we develop a simple,
population-genetic model for the evolution of genetic architectures. Our model
predicts that traits under moderate selection should be encoded by many loci
with highly variable effects, whereas traits under either weak or strong
selection should be encoded by relatively few loci. We compare these
theoretical predictions to qualitative trends in the genetics of human traits,
and to systematic data on the genetics of gene expression levels in yeast. Our
analysis provides an evolutionary explanation for broad empirical patterns in
the genetic basis of traits, and it introduces a single framework that unifies
the diversity of observed genetic architectures, ranging from Mendelian to
Fisherian.
