The selective values of alleles in a molecular network model are context dependent.
Classical quantitative genetics has applied linear modeling to the problem of mapping genotypic to phenotypic variation. Much of this theory was developed prior to the availability of molecular biology. The current understanding of the mechanisms of gene expression indicates the importance of nonlinear effects resulting from gene interactions. We provide a bridge between genetics and gene network theories by relating key concepts from quantitative genetics to the parameters, variables, and performance functions of genetic networks. We illustrate this methodology by simulating the genetic switch controlling galactose metabolism in yeast and its response to selection for a population of individuals. Results indicate that genes have heterogeneous contributions to phenotypes and that additive and nonadditive effects are context dependent. Early cycles of selection suggest strong additive effects attributed to some genes. Later cycles suggest the presence of strong context-dependent nonadditive effects that are conditional on the outcomes of earlier selection cycles. A single favorable allele cannot be consistently identified for most loci. These results highlight the complications that can arise with the presence of nonlinear effects associated with genes acting in networks when selection is conducted on a population of individuals segregating for the genes contributing to the network.
Peccoud
Jean
J
Pioneer Hi-Bred International, Johnston, Iowa 50131-0552, USA. jean.peccoud@pioneer.com
Velden
Kent Vander
KV
Podlich
Dean
D
Winkler
Chris
C
Arthur
Lane
L
Cooper
Mark
M
D000483:Alleles; D003198:Computer Simulation; D005690:Galactose / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005828:Genetics, Population; D005838:Genotype; D008958:Models, Molecular; D017711:Nonlinear Dynamics; D010641:Phenotype; D012641:Selection, Genetic; D015003:Yeasts
D005690:Galactose