Wiring between close nodes in biological networks evolves more quickly than between distant nodes

Abstract

Protein-protein interaction networks and metabolic networks change across species as a result of a wide range of evolutionary processes; these processes result in the accumulation of network differences between species. The rate at which biological networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and incomplete nature of network data across species. We present an alternative approach to study network evolution using drug-drug interactions (DDIs) as a proxy for network topology. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying biological network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data on a high throughput study in gram-negative bacteria. In parallel, we mapped drugs with known targets in biological networks and calculated network distance, connectivity, and adjacency between targets. Our findings indicate that the targets of synergistic DDIs are closer in biological networks than other types of DDIs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer in biological networks evolve at a faster rate. Future studies of network evolution may use DDI data and phylogenetic comparative methods to gain larger-scale perspectives on the details of network evolution within and between species.