Using phenotypic plasticity to understand the structure and evolution of the genotype-phenotype map.

Deciphering the genotype-phenotype map necessitates relating variation at the genetic level to variation at the phenotypic level. This endeavour is inherently limited by the availability of standing genetic variation, the rate of spontaneous mutation to novo genetic variants, and possible biases associated with induced mutagenesis. An interesting alternative is to instead rely on the environment as a source of variation. Many phenotypic traits change plastically in response to the environment, and these changes are generally underlain by changes in gene expression. Relating gene expression plasticity to the phenotypic plasticity of more integrated organismal traits thus provides useful information about which genes influence the development and expression of which traits, even in the absence of genetic variation. We here appraise the prospects and limits of such an environment-for-gene substitution for investigating the genotype-phenotype map. We review models of gene regulatory networks, and discuss the different ways in which they can incorporate the environment to mechanistically model phenotypic plasticity and its evolution. We suggest that substantial progress can be made in deciphering this genotype-environment-phenotype map, by connecting theory on gene regulatory network to empirical patterns of gene co-expression, and by more explicitly relating gene expression to the expression and development of phenotypes, both theoretically and empirically.