Fisher's model and the genomics of adaptation: restricted pleiotropy, heterogenous mutation, and parallel evolution

Evolution. 2010 Nov;64(11):3213-31. doi: 10.1111/j.1558-5646.2010.01058.x.


Genetic theories of adaptation generally overlook the genes in which beneficial substitutions occur, and the likely variation in their mutational effects. We investigate the consequences of heterogeneous mutational effects among loci on the genetics of adaptation. We use a generalization of Fisher's geometrical model, which assumes multivariate Gaussian stabilizing selection on multiple characters. In our model, mutation has a distinct variance-covariance matrix of phenotypic effects for each locus. Consequently, the distribution of selection coefficients s varies across loci. We assume each locus can only affect a limited number of independent linear combinations of phenotypic traits (restricted pleiotropy), which differ among loci, an effect we term "orientation heterogeneity." Restricted pleiotropy can sharply reduce the overall proportion of beneficial mutations. Orientation heterogeneity has little impact on the shape of the genomic distribution, but can substantially increase the probability of parallel evolution (the repeated fixation of beneficial mutations at the same gene in independent populations), which is highest with low pleiotropy. We also consider variation in the degree of pleiotropy and in the mean s across loci. The latter impacts the genomic distribution of s, but has a much milder effect on parallel evolution. We discuss these results in the light of evolution experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution*
  • Cloning, Molecular
  • Computer Simulation
  • DNA Mutational Analysis
  • Evolution, Molecular
  • Genomics
  • Models, Genetic
  • Models, Statistical
  • Mutation*
  • Normal Distribution
  • Phenotype
  • Polymerase Chain Reaction