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Adaptive evolution of bacterial metabolic networks by horizontal gene transfer

Nature Genetics volume 37, pages 1372–1375 (2005)Cite this article

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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References

  1. Schmidt, S., Sunyaev, S., Bork, P. & Dandekar, T. Metabolites: a helping hand for pathway evolution? Trends Biochem. Sci. 28, 336–341 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Lawrence, J.G. & Hendrickson, H. Lateral gene transfer: when will adolescence end? Mol. Microbiol. 50, 739–749 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Lerat, E., Daubin, V., Ochman, H. & Moran, N.A. Evolutionary origins of genomic repertoires in bacteria. PLoS Biol. 3, e130 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Teichmann, S.A. et al. The evolution and structural anatomy of the small molecule metabolic pathways in Escherichia coli. J. Mol. Biol. 311, 693–708 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Rison, S.C., Teichmann, S.A. & Thornton, J.M. Homology, pathway distance and chromosomal localization of the small molecule metabolism enzymes in Escherichia coli. J. Mol. Biol. 318, 911–932 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Alves, R., Chaleil, R.A. & Sternberg, M.J. Evolution of enzymes in metabolism: a network perspective. J. Mol. Biol. 320, 751–770 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Reed, J.L., Vo, T.D., Schilling, C.H. & Palsson, B.O. An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biol. 4, R54 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lawrence, J.G., Hartl, D.L. & Ochman, H. Molecular considerations in the evolution of bacterial genes. J. Mol. Evol. 33, 241–250 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Ochman, H. & Groisman, E.A. The origin and evolution of species differences in Escherichia coli and Salmonella typhimurium. EXS 69, 479–493 (1994).

    CAS  PubMed  Google Scholar 

  10. Snel, B., Bork, P. & Huynen, M.A. Genomes in flux: the evolution of archaeal and proteobacterial gene content. Genome Res. 12, 17–25 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Mirkin, B.G., Fenner, T.I., Galperin, M.Y. & Koonin, E.V. Algorithms for computing parsimonious evolutionary scenarios for genome evolution, the last universal common ancestor and dominance of horizontal gene transfer in the evolution of prokaryotes. BMC Evol. Biol. 3, 2 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Boussau, B., Karlberg, E.O., Frank, A.C., Legault, B.A. & Andersson, S.G. Computational inference of scenarios for alpha-proteobacterial genome evolution. Proc. Natl. Acad. Sci. USA 101, 9722–9727 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lawrence, J.G. & Ochman, H. Molecular archaeology of the Escherichia coli genome. Proc. Natl. Acad. Sci. USA 95, 9413–9417 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Keseler, I.M. et al. EcoCyc: a comprehensive database resource for Escherichia coli. Nucleic Acids Res. 33, D334–D337 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Papp, B., Pál, C. & Hurst, L.D. Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast. Nature 429, 661–664 (2004).

    Article  CAS  PubMed  Google Scholar 

  16. Hooper, S.D. & Berg, O.G. On the nature of gene innovation: duplication patterns in microbial genomes. Mol. Biol. Evol. 20, 945–954 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Gerdes, S.Y. et al. Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J. Bacteriol. 185, 5673–5684 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Thatcher, J.W., Shaw, J.M. & Dickinson, W.J. Marginal fitness contributions of nonessential genes in yeast. Proc. Natl. Acad. Sci. USA 95, 253–257 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Price, N.D., Reed, J.L. & Palsson, B.O. Genome-scale models of microbial cells: evaluating the consequences of constraints. Nat. Rev. Microbiol. 2, 886–897 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Segre, D., Vitkup, D. & Church, G.M. Analysis of optimality in natural and perturbed metabolic networks. Proc. Natl. Acad. Sci. USA 99, 15112–15117 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Reed, J.L. & Palsson, B.O. Genome-scale in silico models of E. coli have multiple equivalent phenotypic states: assessment of correlated reaction subsets that comprise network states. Genome Res. 14, 1797–1805 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Taoka, M. et al. Only a small subset of the horizontally transferred chromosomal genes in Escherichia coli are translated into proteins. Mol. Cell. Proteomics 3, 780–787 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Burgard, A.P., Nikolaev, E.V., Schilling, C.H. & Maranas, C.D. Flux coupling analysis of genome-scale metabolic network reconstructions. Genome Res. 14, 301–312 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Snel, B. & Huynen, M.A. Quantifying modularity in the evolution of biomolecular systems. Genome Res. 14, 391–397 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Salgado, H. et al. RegulonDB (version 4.0): transcriptional regulation, operon organization and growth conditions in Escherichia coli K-12. Nucleic Acids Res. 32, D303–D306 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jain, R., Rivera, M.C. & Lake, J.A. Horizontal gene transfer among genomes: the complexity hypothesis. Proc. Natl. Acad. Sci. USA 96, 3801–3806 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Almaas, E., Kovacs, B., Vicsek, T., Oltvai, Z.N. & Barabasi, A.L. Global organization of metabolic fluxes in the bacterium Escherichia coli. Nature 427, 839–843 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. von Mering, C. et al. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 33, D433–D437 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Forster, J., Famili, I., Fu, P., Palsson, B.O. & Nielsen, J. Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res. 13, 244–253 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kellis, M., Birren, B.W. & Lander, E.S. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428, 617–624 (2004).

    Article  CAS  PubMed  Google Scholar 

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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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Authors and Affiliations

  1. European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, D-69012, Germany

    Csaba Pál & Martin J Lercher

  2. MTA, Theoretical Biology and Ecology Research Group, Eötvös Loránd University, Budapest, H-1117, Hungary

    Csaba Pál & Balázs Papp

  3. Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK

    Balázs Papp

  4. Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK

    Martin J Lercher

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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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