Roles of metabolites and inter-species conservation. To quantify the relation between roles and conservation, we calculate the loss rate plost(R) of each metabolite (see Methods). Each thin line in the graph corresponds to a comparison between two species. Because we are interested in metabolites that are present in some species but missing in others, metabolic networks of species within the same superkingdom—bacteria, eukaryotes and archaea—are usually too similar to provide statistically sound information, especially for roles containing only a few metabolites. Therefore, we consider in our analysis only pairs of species that belong to different superkingdoms. The thick line is the average over all pairs of species. The loss rate plost(R) is maximum for ultra-peripheral (R1) nodes and minimum for connector hubs (R6). Provincial hubs (R5) have a significantly and consistently higher plost(R) than non-hub connectors (R3), even though the within-module degree and the total degree of provincial hubs is larger. Note that, out of the total 48 pair comparisons, only in two cases is plost(R) lower for provincial hubs than for non-hub connectors, whereas the opposite is true in 44 cases. a, b, Results obtained for the MZ database (a) and the complete KEGG database (b).