Genetic pleiotropy in Saccharomyces cerevisiae quantified by high-resolution phenotypic profiling

Genetic pleiotropy, the ability of a mutation ina single gene to give rise to multiple phenotypic outcomes,constitutes an important but incompletelyunderstood biological phenomenon. We used a highresolutionand high-precision phenotypic profiling approachto quantify the fitness contribution of genes onthe five smallest yeast chromosomes during differentforms of environmental stress, selected to probe a widediversity of physiological features. We found that theextent of pleiotropy is much higher than previouslyclaimed; 17% of the yeast genes were pleiotropicwhereof one-fifth were hyper-pleiotropic. Pleiotropicgenes preferentially participate in functions related todetermination of protein fate, cell growth and morphogenesis,signal transduction and transcription. Contraryto what has earlier been proposed we did not findexperimental evidence for slower evolutionary rate ofpleiotropic genes/proteins. We also refute the existenceof phenotypic islands along chromosomes but report ona remarkable loss both of pleiotropy and of phenotypicpenetrance towards chromosomal ends. Thus, the herereported features of pleiotropy both have implicationson our understanding of evolutionary processes as wellas the mechanisms underlying disease