directional epistasis

Pavlicev M, Le Rouzic A, Cheverud JM, Wagner GP & Hansen TF 2010 Directionality of epistasis in a murine intercross population. Genetics, in press.
doi:10.1534/genetics.110.118356

  • directional epistasis describes a situation in which epistasis consistently increases or decreases the effect of allele substitutions
  • thereby affecting the amount of additive genetic variance available for selection in a given direction
  • epistasis is present when the effect of a genetic substitution depends on the genotypes at other loci
  • at the population level, this means that average allelic effects change as allele frequencies at other loci change, and thus that gene effects can evolve
  • the evolutionary significance of epistasis has been recognized mainly in relation to the allele-frequency changes that are caused by genetic drift
  • whereas the epistatic effects under directional selection have been treated only recently
  • technically, the effects of epistatic interaction can be considered as having two aspects
  • the architecture itself
  • i.e., the existence of a nonadditive component, the so-called functional aspect
  • the effect of allele frequency on genetic variance
  • i.e., the statistical aspect
  • the traditional population-genetic approach to selection response initially emphasized additive genetic variance and treated any variance unexplained by the additive effects, including variance due to interactions within or between loci, as residual variance
  • later this model was extended to account for epistasis
  • the interaction component of this residual variance is dependent on population allele frequencies at the interacting loci
  • Falconer (1960) described the effect of allele frequencies on the statistical measure of average allelic effect
  • Cheverud and Routman (1995) explored the analogous effect at the two-locus level, leading to distinction between allele-frequency-dependent statistical epistasis (contributing to epistatic variance) on population level, and allele-frequency-independent physiological (or functional) epistasis on the individual level
  • physiological epistasis describes the genetic architecture of a given phenotype defining the potential for epistatic effects
  • statistical epistasis describes the realization of individual-level epistatic effects in terms of allele-frequency-dependent genetic variance components
  • several authors have worked out tools to estimate gene interaction effects at the individual level independently of the allele frequencies to distinguish between the physiological and statistical epistasis
  • Hansen and Wagner (2001a) introduced the notion of directionality of epistasis to emphasize the importance of the pattern of epistatic architecture for the system's evolvability
  • directionality measures the consistency of epistatic effects on additive variance for a specific locus and trait across the genome, given a defined reference genotype
  • it describes whether epistasis tends to enhance or diminish the additive effects of interacting loci on a trait in a specified phenotypic direction
  • the directionality of epistasis can be a major determinant of evolution on time scales beyond a few generations
  • positive directional epistasis increases additive variance and the response to positive selection relative to that predicted by the additive genetic effects alone
  • negative directional epistasis tends to decrease the response to selection in that same phenotypic direction
  • an absence of epistatic directionality occurs when positive and negative directional epistatic effects cancel out on average