Epistasis Blog

From the Computational Genetics Laboratory at Dartmouth Medical School (www.epistasis.org)

Tuesday, May 22, 2007

Genetic Programming Theory and Practice V

I just returned from the annual Genetic Programming Theory and Practice (GPTP) workshop hosted by the Center for the Study of Complex Systems at the University of Michigan (my alma mater). This is the second time I have been invited to attend and present a paper at GPTP and I can honestly say it is my favorite scientific conference. The goal is to bring GP theorists together with those on the front lines of solving complex problems for an exchange of ideas. The workshop this year focused on a number of issues including building more complexity into GP algorithms. That is, can we develop GP algorithms that more closely mirror the complexity of real biological systems? This line of discussion was motivated by the keynote presentation by Dr. Wolfgang Banzaf from Memorial University in Canada. Dr. Banzaf presented ideas from his recent Nature Reviews Genetics paper that I mentioned here previously. I presented our work on SyMod and our recent paper in Human Heredity on Symbolic Modeling.

Monday, May 07, 2007

New Epistasis Papers

Several new papers in the April Nature Genetics explore epistasis in model systems.

Jasnos L, Korona R. Epistatic buffering of fitness loss in yeast double deletion strains. Nat Genet. 2007 Apr;39(4):550-4. [PubMed]

Interactions between deleterious mutations have been insufficiently studied, despite the fact that their strength and direction are critical for understanding the evolution of genetic recombination and the buildup of mutational load in populations. We compiled a list of 758 yeast gene deletions causing growth defects (from the Munich Information Center for Protein Sequences database and ref. 7). Using BY4741 and BY4742 single-deletion strains, we carried out 639 random crosses and assayed growth curves of the resulting progeny. We show that the maximum growth rate averaged over strains lacking deletions and those with double deletions is higher than that of strains with single deletions, indicating a positive epistatic effect. This tendency is shared by genes belonging to a variety of functional classes. Based on our data and former theoretical work, we suggest that epistasis is likely to diminish the negative effects of mutations when the ability to produce biomass at high rates contributes significantly to fitness.

Martin G, Elena SF, Lenormand T. Distributions of epistasis in microbes fit predictions from a fitness landscape model. Nat Genet. 2007 Apr;39(4):555-60. [PubMed]

How do the fitness effects of several mutations combine? Despite its simplicity, this question is central to the understanding of multilocus evolution. Epistasis (the interaction between alleles at different loci), especially epistasis for fitness traits such as reproduction and survival, influences evolutionary predictions "almost whenever multilocus genetics matters". Yet very few models have sought to predict epistasis, and none has been empirically tested. Here we show that the distribution of epistasis can be predicted from the distribution of single mutation effects, based on a simple fitness landscape model. We show that this prediction closely matches the empirical measures of epistasis that have been obtained for Escherichia coli and the RNA virus vesicular stomatitis virus. Our results suggest that a simple fitness landscape model may be sufficient to quantitatively capture the complex nature of gene interactions. This model may offer a simple and widely applicable alternative to complex metabolic network models, in particular for making evolutionary predictions.