Academic journal article Genetics

Interactions between Stressful Environment and Gene Deletions Alleviate the Expected Average Loss of Fitness in Yeast

Academic journal article Genetics

Interactions between Stressful Environment and Gene Deletions Alleviate the Expected Average Loss of Fitness in Yeast

Article excerpt

ABSTRACT

The conjecture that the deleterious effects of mutations are amplified by stress or interaction with one another remains unsatisfactorily tested. It is now possible to reapproach this problem systematically by using genomic collections of mutants and applying stress-inducing conditions with a well-recognized impact on metabolism. We measured the maximum growth rate of single- and double-gene deletion strains of yeast in several stress-inducing treatments, including poor nutrients, elevated temperature, high salinity, and the addition of caffeine. The negative impact of deletions on the maximum growth rate was relatively smaller in stressful than in favorable conditions. In both benign and harsh environments, double-deletion strains grew on average slightly faster than expected from a multiplicative model of interaction between single growth effects, indicating positive epistasis for the rate of growth. This translates to even higher positive epistasis for fitness defined as the number of progeny. We conclude that the negative impact of metabolic disturbances, regardless of whether they are of environmental or genetic origin, is absolutely and relatively highest when growth is fastest. The effect of further damages tends to be weaker. This results in an average alleviating effect of interactions between stressful environment and gene deletions and among gene deletions.

RECENT experiments suggest that the genomic rate of spontaneous deleterious mutation is high (Denver et al. 2004; Haag-Liautard et al. 2007). Spontaneous mutagenesis must be countered by purging selection-that is, the enhanced mortality or reduced fecundity of bearers of mutations-or offset by compensatory mutations (Silander et al. 2007). It has been repeatedly proposed that a harsh environment, or stress, is likely to aid selection by imposing demands unbearable for individuals weakened by mutations. This simple and intuitively appealing assumption is supported by the results of some experiments demonstrating that the negative effects of random mutations are higher under adverse physical conditions or severe competition (Kondrashov andHoule 1994; Shabalina et al. 1997; Korona 1999; Vassilieva et al. 2000; Szafraniec et al. 2001; Yang et al. 2001; Fry and Heinsohn 2002). However, not all studies confirm this expectation (Fry et al. 1996; Martin and Lenormand 2006) and an opposite effect has also been described (Kishony and Leibler 2003). Moreover, the reported cases of aggravation of deleterious effects in harsh environments are difficult to interpret. Earlier studies often involved organisms with large and unknown numbers of mutations. It is thus unclear whether stress exposes more mutations or increases their average effects (Szafraniec et al. 2001). Finally, it is possible that environmental stress may promote negative (lowering fitness) genetic interactions among deleterious mutations. This direction of epistasis probably does not dominate under normal environmental conditions (De Visser and Elena 2007; Kouyos et al. 2007; Jasnos and Korona 2007). However, it is unsure whether the average effect of epistasis can change under stress (You and Yin 2002; Kishony and Leibler 2003; Cooper et al. 2005; Killick et al. 2006). In sum, the basic characteristics of deleteriousmutations are insufficiently recognized, especially when the changeability of the environment is taken into account. It therefore remains unclear whether the accumulation of deleterious mutations can endanger the existence of populations (Kimura and Maruyama 1966; Crow and Kimura 1979; Schultz and Lynch 1997) and whether the widespread occurrence of genetic recombination and sex is an evolutionary response to this threat (Otto and Lenormand 2002).

We chose the organism, mutations, and environments specifically to overcome or reduce the problems typically met in earlier studies. We used isogenic strains of the budding yeast with none, one, or two gene deletions. The use of gene deletions guaranteed that each introduced alteration meant the complete loss of a protein in all studied environments. …

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