Influence of pathway topology and functional class on the molecular evolution of human metabolic genes.

For both ontology-based and compound-based classification, we find significant differences among different functional classes in the evolutionary rates dN , and dN/dS (with dS close to significance).

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When we compare the evolutionary rates of these classes through a KW test we find highly significant differences with a clear gradient of selective constraints in which central routes of the core metabolism are more constrained (lower dN and dN/dS ) than the ones in the second layer which, in turn, are more constrained than those of the more peripheral layer ( Fig 2 and S3 Fig ).

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