Network Architecture and Mutational Sensitivity of the C. elegans Metabolome

Abstract

A fundamental issue in evolutionary systems biology is understanding the relationship between the topological architecture of a biological network, such as a metabolic network, and the evolution of the network. The rate at which an element in a metabolic network accumulates genetic variation via new mutations depends on both the size of the mutational target it presents and its robustness to mutational perturbation. Quantifying the relationship between topological properties of network elements and the mutability of those elements will facilitate understanding the variation in and evolution of networks at the level of populations and higher taxa.\n\nWe report an investigation into the relationship between two topological properties of 29 metabolites in the C. elegans metabolic network and the sensitivity of those metabolites to the cumulative effects of spontaneous mutation. The relationship between several measures of network centrality and sensitivity to mutation is weak, but point estimates of the correlation between network centrality and mutational variance are positive, with only one exception. There is a marginally significant correlation between core number and mutational heritability. There is a small but significant negative correlation between the shortest path length between a pair of metabolites and the mutational correlation between those metabolites.\n\nPositive association between the centrality of a metabolite and its mutational heritability is consistent with centrally-positioned metabolites presenting a larger mutational target than peripheral ones, and is inconsistent with centrality conferring mutational robustness, at least in toto. The weakness of the correlation between shortest path length and the mutational correlation between pairs of metabolites suggests that network locality is an important but not overwhelming factor governing mutational pleiotropy. These findings provide necessary background against which the effects of other evolutionary forces, most importantly natural selection, can be interpreted.