Marginal fitness contributions of nonessential genes in yeast

Abstract

Analysis of the complete genome sequence of Saccharomyces cerevisiae confirms and extends earlier evidence that a majority of yeast genes are not essential, at least under laboratory conditions. Many fail to yield a discernible mutant phenotype even when disrupted. Genes not subject to natural selection would accumulate inactivating mutations, so these "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 duplicated in the laboratory and would have conditional phenotypes if tested appropriately. (ii) They make small, but significant, contributions to fitness even under routine growth conditions, but the effects are not large 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 their wild-type progenitor. A substantial majority of mutant strains that lack obvious defects nevertheless are at a significant selective disadvantage just growing on rich medium under normal conditions. This result has important implications for efforts to understand the functions of novel genes revealed by sequencing projects.

Figure 1

Representative competition experiments. (A and C) The decline in frequency of the disruption mutants TD64 and TD63, respectively, as a function of generations in culture. Note the different scales. (B and D) The natural log of the ratio of the disruption strain to the wild-type strain for the same data, each with a line that is the least-squares fit with a slope that provides an estimate of the selection coefficient (s) reported in Table 1.