The genotype-phenotype map of yeast complex traits: basic parameters and the role of natural selection.

Most phenotypic traits are controlled by many genes, but a global picture of the genotype-phenotype map (GPM) is lacking. For example, in no species do we know generally how many genes affect a trait and how large these effects are. It is also unclear to what extent GPMs are shaped by natural selection. Here we address these fundamental questions using the reverse genetic data of 220 morphological traits in 4,718 budding yeast strains, each of which lacks a nonessential gene. We show that 1) the proportion of genes affecting a trait varies from <1% to >30%, averaging 6%, 2) most traits are impacted by many more small-effect genes than large-effect genes, and 3) the mean effect of all nonessential genes on a trait decreases precipitously as the estimated importance of the trait to fitness increases. An analysis of 3,116 yeast gene expression traits in 754 gene-deletion strains reveals a similar pattern. These findings illustrate the power of genome-wide reverse genetics in genotype-phenotype mapping, uncover an enormous range of genetic complexity of phenotypic traits, and suggest that the GPM of cellular organisms has been shaped by natural selection for mutational robustness.