Population and quantitative genetics of regulatory networks

I evolved boolean regulatory networks in a computer simulation. I varied mu tation, recombination, the size of the network, and the number of connectio ns per node. I measured the performance of networks and the heritability an d epistasis of genetic effects. Networks of intermediate connectivity perfo rmed best. The distinction between metabolic and quantitative genetic addit ivity explained some of the variation in performance. Metabolic additivity describes the interaction between changes in a single network, whereas quan titative genetic additivity measures the consistency of phenotypic effect c aused by gene substitution in randomly chosen members of the population. I analysed metabolic additivity by the distribution of epistatic effects of p airs of mutations in individual networks. I measured quantitative genetic a dditivity by heritability. Highly connected networks had greater metabolic additivity for perturbations to individual networks, but had lower additivi ty when measured by the average effect of a gene substitution (heritability ). The lower heritability of highly connected nets appeared to reduce the e ffectiveness of recombination in searching evolutionary space. (C) 1999 Aca demic Press.