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Adaptive evolution of bacterial metabolic networks by horizontal gene transfer

Abstract

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.

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Figure 1: Comparison of duplicate genes in the metabolic networks of yeast (S. cerevisiae)29 and E. coli.
Figure 2
Figure 3: Proteins at the periphery of the metabolic network are much more likely to have undergone horizontal gene transfer into the E. coli lineage since its split from the Vibrio lineage.

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Acknowledgements

We thank P. Bork, L. Hurst and S. McWeeney for suggestions on previous versions of the manuscript; C. von Mering for discussions and providing early access to the updated STRING database; and E. Nikolaev for discussions on flux coupling analysis. C.P. and B.P. are supported by the Hungarian Scientific Research Fund. B.P. is a Fellow of the Human Frontier Science Program. C.P. acknowledges support by an EMBO Long-Term Fellowship. M.J.L. acknowledges support by the Deutsche Forschungsgemeinschaft.

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Correspondence to Martin J Lercher.

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Supplementary information

Supplementary Fig. 1

Phylogenetic tree of 56 proteobacterial species. (PDF 19 kb)

Supplementary Fig. 2

Virus- and transposon-related functions of transferred genes. (PDF 77 kb)

Supplementary Fig. 3

Dependence of GC and codon usage bias on transfer age. (PDF 71 kb)

Supplementary Table 1

Transfer numbers on each phylogenetic branch. (PDF 24 kb)

Supplementary Table 2

Supplementary results. (PDF 29 kb)

Supplementary Table 3

Growth conditions and biomass composition for FBA. (PDF 24 kb)

Supplementary Methods (PDF 38 kb)

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Pál, C., Papp, B. & Lercher, M. Adaptive evolution of bacterial metabolic networks by horizontal gene transfer. Nat Genet 37, 1372–1375 (2005). https://doi.org/10.1038/ng1686

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