Dominance, Pleiotropy and Metabolic Structure

Peter D. Keightley ¹ and Henrik Kacser ¹

¹ Department of Genetics, University of Edinburgh, Edinburgh EH9 3JN, Scotland

It is a common observation that most mutants have similar dominance relations for all the characters they are known to affect. As a model of pleiotropic effects we investigate a branched pathway where the two outputs represent two characters whose variation is affected by changes in any of the genetically specified enzymes in the system. We consider the effects on the phenotype (fluxes or intermediate metabolites) of substitutions at one locus represented by enzyme activities of the two homozygotes (mutant and wild type) and that of the heterozygote. Dominance indices for the characters pleiotropically connected by the metabolic system are calculated. We show that if enzymes behave `linearly,' (first order), that is if saturation and feedback inhibition or other nonlinearities are absent, all fluxes and pools have identical dominance relations. The presence of such nonlinearity, however, leads to differences in dominance between different characters and we define the conditions where such differences can be important.

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