MARGINAL FITNESS CONTRIBUTIONS OF NONESSENTIAL GENES IN YEAST

Analysis of the complete genome sequence of Saccharomyces cerevisiae c onfirms and extends earlier evidence that a majority of yeast genes ar e not essential, at least under laboratory conditions. Many fail to yi eld a discernible mutant phenotype even when disrupted. Genes not subj ect to natural selection would accumulate inactivating mutations, so t hese ''cryptic'' genes must have functions that are overlooked by the standard methods of yeast genetics. Two explanations seem possible: (i ) They have important functions only in environments not yet duplicate d in the laboratory and would have conditional phenotypes if tested ap propriately. (ii) They make small, but significant, contributions to f itness even under routine growth conditions, but the effects are not l arge enough to be detected by conventional methods. We have tested the second ''marginal benefit'' hypothesis by measuring the fitnesses of a random collection of disruption mutants in direct competition with t heir wild-type progenitor. A substantial majority of mutant strains th at lack obvious defects nevertheless are at a significant selective di sadvantage just growing on rich medium under normal conditions. This r esult has important implications for efforts to understand the functio ns of novel genes revealed by sequencing projects.