Adaptive evolution of bacterial metabolic networks by horizontal gene transfer

Numerous studies have considered the emergence of metabolic pathways1, but the modes of recent evolution of metabolic networks are poorly understood. Here, we integrate comparative genomics with flux balance analysis to examine (i) the contribution of different genetic mechanisms to network growth in bacteria, (ii) the selective forces driving network evolution and (iii) the integration of new nodes into the network. Most changes to the metabolic network of Escherichia coli in the past 100 million years are due to horizontal gene transfer, with little contribution from gene duplicates. Networks grow by acquiring genes involved in the transport and catalysis of external nutrients, driven by adaptations to changing environments. Accordingly, horizontally transferred genes are integrated at the periphery of the network, whereas central parts remain evolutionarily stable. Genes encoding physiologically coupled reactions are often transferred together, frequently in operons. Thus, bacterial metabolic networks evolve by direct uptake of peripheral reactions in response to changed environments.