The involvement of the RAD6 gene in starvation-induced reverse mutation in Saccharomyces cerevisiae

Abstract

The accumulation of Ade+ revertants during adenine starvation and Trp+ revertants during tryptophan starvation in haploid polyauxotrophic strains of Saccharomyces cerevisiae occurs in a time-dependent manner. Accumulation of revertants is enhanced in Rad6- strains, suggesting that starvation-induced reversion is influenced by some of the RAD6 gene functions. The higher frequency of adaptive reversions in Rad6- strains is somewhat influenced by, but does not totally depend on, the genetic background. Therefore, the RAD6 gene product is involved in maintaining a low level not only of spontaneous mutation but also of starvation-induced reversion. The starvation-induced Ade+ and Trp+ reversions both appear to be adaptive. The analysis of growth characteristics and the genotype of revertants shows a difference between early and late-appearing revertants. These results support the hypothesis that the adaptivity of starvation-induced reversion is based on the selective fixation of random mutations, and particularly on transcription-enhanced repair and/or mutagenesis processes.

Inherited adaptation of genome‐rewired cells in response to a challenging environment

“…No doubt that the fraction of cells, which adapted on the plates, either in solid or in liquid medium experiments, was unprecedentedly high and, thus, stands in contrast to previous evolutionary experiments that found much lower rates (one in 10 5 -10 9 cells) at which adaptive phenotypes rose under stressful conditions (Paquin and Adams, 1983;Lenski and Travisano, 1994;Storchová et al, 1998;Elena and Lenski, 2003;Heidenreich, 2007). In previous studies adaptive phenotypes were observed in rates that matched the rates of genetic mutations and, indeed, in several such studies, mutations were found to be the causative agents of the new phenotypes.…”

“…However, up until now, in spite of major efforts to identify such and although some cases are still under debate, there is no conclusive evidence in the literature for the existence of adaptive mutations (Cairns et al, 1988;Cairns and Foster, 1991;Steele and Jinks-Robertson, 1992;Hall, 1998aHall, , 1998bRosenberg, 2001;Roth et al, 2006). Even if adaptive mutations were in consensus, in previous studies revertants in response to stressful conditions and induced adaptive mutations were reported to occur only in a minute fraction ͑ϳ10 −6 ͒ of the population (Storchová et al, 1998;Heidenreich, 2007) and not in 50% of the cells such as in our experiments. Other phenomena with some resemblance to what we described here were also studied.…”

Adaptive Mutation inSaccharomyces cerevisiae

“…Unfortunately, observations of adaptive mutation in S. cerevisiae may therefore not have received the proper attention in the past and are now difficult to evaluate for their significance. (Storchova et al, 1997(Storchova et al, , 1998Rojas Gil and Vondrejs, 1999) …”

“…Although the inoculum cells are asynchronous at the beginning, the abrupt lack of the essential nutrient causes the transition to starvationinduced cell cycle arrest during the first few hours after plating. Residual proliferation due to internal reserves of the essential nutrient may lead to a doubling of the cell number but is limited to the first day of incubation (Heidenreich and Wintersberger, 1997;Storchova et al, 1998). Pre-existing proliferation-dependent revertants normally form colonies no later than day 3 (excluding extragenic suppressors, see Sections 2.4 and 3.1.1).…”

“…"Selection-induced mutation" (Hall, 1992;Heidenreich and Wintersberger, 1998) and "starvation-induced mutation" (Storchova et al, 1997(Storchova et al, , 1998Rojas Gil and Vondrejs, 1999) allege that the selective conditions start, rather than terminate, a mutagenic process, which putatively is not the case. "Starvation-associated mutation" (Storchova and Vondrejs, 1999;Cejka et al, 2001) does not have this bias, but expresses a narrowing to the most common selective condition.…”