Parameters of mutation in yeast

Estimating parameters of mutations is an important avenue of research in evolutionary biology.  Our interest lies in both underlying mutation rate and spectrum and in the effects of these mutations.  in particular, we wish to estimate the genome-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 adaptation, the speed of Muller's ratchet, the level of inbreeding depression, the evolution of senescence, and many other evolutionary phenomena (see Lynch et al. 1999 for review).  Several years ago, we performed a 2000 (asexual) generation, mutation-accumulation experiment 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.  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.  Currently, in collaboration with Mark Siegal and Dmitri Petrov, we are sequencing the MA lines to estimate the spectrum of mutations and we are also determining the molecular basis of the lethal and highly deleterious mutations that have accumulated in some lines. 

Trade-offs across life history components in yeast

Genetic trade-offs across life history traits can constrain adaptation. Such trade-offs will manifest as negative genetic correlations, which can be caused by negative pleiotropy. In our MA lines, we have looked for evidence for pleiotropy among accumulated mutations and find that for most, there is no evidence.  However, the MA lines that have zero fitness (i.e. lethality) for any one fitness component do show evidence for pleiotropy among accumulated mutations.  For one MA line, pleiotropy was negative, and we are currently following up on this result.

The evolution of chromosomal architecture

We are currently using both analytical models and simulations to address the evolution of chromosomal architecture.  We are particularly interested in the evolution of the distribution of different types of genes along chromosomes. We are currently collaborating with Mike McEachern in a study to examine the chromosomal region near the telomere. In our lab, we are performing simulations while Mike’s lab is doing experiments to elucidate the evolution of the region.  

The Hall Lab

The University of Georgia

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