How to predict epistatic gene interactions

When combined, the effects of mutations in different genes often deviate from what would be expected by looking at them separately. Researchers at the University of Val￨ncia in Spain have shown that an organism's genomic complexity may predict these epistatic gene interactions. ¹ It is a "fascinating new synthesis of published experiments," writes Faculty of 1000 member Richard Lenski of Michigan State University, adding that it is "sure to stimulate empirical and theoretical research for years to come."

"In recent years, many experiments have used viruses, bacteria, fungi, and fruit flies to measure the strength and form of interactions among random mutations. Sanju￡n and Elena synthesize these studies and discover a quite remarkable pattern. Mutations in viruses tend to interact antagonistically, such that two deleterious mutations are less harmful together than predicted by summing their separate effects. In flies, this trend is reversed, with deleterious mutations tending toward synergistic interactions, so that the combined effect is worse than expected from their individual effects. The data as a whole suggest a remarkable scaling relationship of average epistasis with genome complexity. Understanding how interactions between mutations influence fitness is a growing area of research that has broad implications for our understanding of adaptation, speciation, the evolution of sexual reproduction, conservation of endangered species, and more."