Modeling Genetic Architecture: A Multilinear Theory of Gene Interaction

The map from genotype to phenotype is an exceedingly complex function of central importance in biology. In this work we derive and analyze a mathematically tractable model of the genotype–phenotype map that allows for any order of gene interaction. By assuming that the alterations of the effect of a gene substitution due to changes in the genetic background can be described as a linear transformation, we show that the genotype–phenotype map is a sum of linear and multilinear terms of operationally defined “reference” effects at each locus. The “multilinear” model is used to study the effect of epistasis on quantitative genetic variation, on the response to selection, and on genetic canalization. It is shown how the model can be used to estimate the strength of “functional” epistasis from a variety of genetic experiments.