Research

Can epistasis explain the evolution and maintenance of sex and recombination in yeast?

Despite over half a century of intense research, understanding the evolution of sex and recombination remains an unanswered question.  While several hypotheses have been examined theoretically, a general explanation has proven elusive (see Otto and Lenormand 2004 and deVisser and Elena 2007 for recent reviews).  Several of the hypotheses that have been advanced to explain the evolution of sex and recombination require particular interactions among loci affecting fitness.  Perhaps the most influential of these is Kondrashov’s deterministic mutation hypothesis (Kondrashov 1984, 1988) which states that sexual reproduction will have an advantage when deleterious alleles at different loci exhibit weak synergistic (negative) epistasis.  A second hypothesis emphasizes the importance of dominance by dominance epistasis on the evolution of recombination in diploids with inbreeding (Roze and Lenormand 2005). In this hypothesis, if double homozygotes exhibit very low fitness, relative to their expected fitness, then this effect can favor the evolution of modifiers that increase recombination.  Double homozyotes exhibit low expected fitness when dominance x dominance epistasis is large and negative.

We haved been using yeast to estimate epistasis among deletion mutations at six biosynthetic loci, all of which occur in different biosynthetic pathways. We have generated and scored four components of fitness for all possible combinations of deleterious mutations at the six biosynthetic. Our data allowed us to examine whether estimates of epistasis vary with the fitness component that is measured, whether patterns of multi-locus epistasis differ from that observed between pairs of loci, and whether there is an effect of the number of background mutations on the sign or magnitude of epistasis.  In addition, for every combination of two loci in a mutation-free background, we have also generated all heterozygous genotypes, so that we could partition diploid epistasis into additive x additive, additive x dominance and dominance x dominance epistasis. 

We found that in agreement with previous studies, epistasis is small and shows no bias to synergistic values for growth rate. Epistasis was not significantly different across fitness components indicating that, like haploid growth rate, small values of epistasis are observed for haploid mating efficiency, sporulation efficiency and diploid growth rate.  While the number of background mutations did have an effect on epistasis for mating efficiency and for haploid growth rate, the effect was not in a consistent direction. Dominance by dominance epistasis estimates obtained by partitioning diploid epistasis for growth rates were both positive and negative. With the caveat that our results are based on only six biosynthetic loci, epistasis for fitness is not supported as an explanation for the maintenance of sexual reproduction or the high rate of meiotic recombination in yeast.  

Our studies add to the growing body of work addressing the importance of epistasis for the evolution and maintennace of sexual reproducton.

 Mutation accumulation

Estimating parameters of mutations is an important avenue of research in evolutionary biology (see Lynch et al. 1999 for review).  These parameters include the genom-wide mutation rate (U), the distribution of mutational effects, and the frequency of beneficial mutations.  Values of these parameters have implications for the rate of adpatation, the speed of Muller's ratchet, the level of inbreeding depression, the evolution of senscence, and many other evolutionary phenomena. Several years ago, we performed a 2000 (asexual) generation, mutation-accumulation experiment to estimate parameters of spontaneous mutations affecting fitness in yeast . We measured the growth rate of 151 mutation-accumulation lines to estimate parameters of mutation (Joseph and Hall 2004, Hall et al. 2008).  We found that an unexpectedly high frequency of fitness altering mutations were beneficial.  Similarly to most other MA experiments in  microbes, in these studies we had used a single component, growth rate, to measure fitness.  In recent work, we have built upon our previous work by examining additional components of fitness including sporulation efficiency, spore viability and haploid growth rate.  We have found that these components of fitness also show a high frequency of beneficial mutations. We then examined whether MA lines show any evidence for pleiotropy among accumulated mutations and find that for most, there is none.  However, MA lines that have zero fitness (i.e. lethality) for any one fitness component do show evidence for pleiotropy among accumulated mutations.