Deleterious mutations can have a strong influence on the outcome of evolution. The nature of this influence depends on how mutations combine together to affect fitness. "Negative epistasis" occurs when a new deleterious mutation causes the greatest loss in fitness in a genome that already contains many deleterious mutations. Negative epistasis is a key ingredient for some of the leading hypothe...

Sex dimorphism in recombination is widespread on both sex chromosomes and autosomes. Various hypotheses have been proposed to explain these dimorphisms. Yet no theoretical model has been explored to determine how heterochiasmy--the autosomal dimorphism--could evolve. The model presented here shows three circumstances in which heterochiasmy is likely to evolve: (i) a male-female difference in ha...

BACKGROUND Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. METHODOLOGY We develop a general model for testing high-order epistatic interactions for a complex disease i...

Genetic interactions in fitness are studied by using modifier theory. The effects on fitness of two linked genes are perturbed by alleles at a third linked locus that controls the extent of epistasis in fitness between the first two. This epistasis is determined by a symmetric interaction matrix, and it is shown that a modifier allele that increases epistasis will invade when the linkage betwee...

An optimization problem is often represented with a set of variables, and the interaction between the variables is referred to as epistasis. In this paper, we propose two new measures of epistasis: internal epistasis and external epistasis. Then we show that they can quantify the decomposability of a problem, which has a theoretical meaning about how strongly the problem is independently optimi...

The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process. Using a multitype branching process, the fixation probability of a single non-mutator emerging in a large asexual mutator population is analytically calculated here. The mutato...