Abstract
Horizontal gene transfer is one of the main mechanisms contributing to microbial genome diversification1,2,3. To clarify the overall picture of interspecific gene flow among prokaryotes, we developed a new method for detecting horizontally transferred genes and their possible donors by Bayesian inference with training models for nucleotide composition. Our method gives the average posterior probability (horizontal transfer index) for each gene sequence, with a low horizontal transfer index indicating recent horizontal transfer. We found that 14% of open reading frames in 116 prokaryotic complete genomes were subjected to recent horizontal transfer. Based on this data set, we quantitatively determined that the biological functions of horizontally transferred genes, except mobile element genes, are biased to three categories: cell surface, DNA binding and pathogenicity-related functions. Thus, the transferability of genes seems to depend heavily on their functions.
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References
de la Cruz, F. & Davies, J. Horizontal gene transfer and the origin of species: lessons from bacteria. Trends Microbiol. 8, 128â133 (2000).
Ochman, H., Lawrence, J.G. & Groisman, E.A. Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299â304 (2000).
Lawrence, J.G. Gene transfer in bacteria: speciation without species? Theor. Popul. Biol. 61, 449â460 (2002).
Charlebois, R.L., Beiko, R.G. & Ragan, M.A. Microbial phylogenomics: Branching out. Nature 421, 217 (2003).
Kurland, C.G., Canback, B. & Berg, O.G. Horizontal gene transfer: a critical view. Proc. Natl. Acad. Sci. USA 100, 9658â9662 (2003).
Gogarten, J.P., Doolittle, W.F. & Lawrence, J.G. Prokaryotic evolution in light of gene transfer. Mol. Biol. Evol. 19, 2226â2238 (2002).
Rivera, M.C., Jain, R., Moore, J.E. & Lake, J.A. Genomic evidence for two functionally distinct gene classes. Proc. Natl. Acad. Sci. USA 95, 6239â6244 (1998).
Yap, W.H., Zhang, Z. & Wang, Y. Distinct types of rRNA operons exist in the genome of the actinomycete Thermomonospora chromogena and evidence for horizontal transfer of an entire rRNA operon. J. Bacteriol. 181, 5201â5209 (1999).
Hacker, J. & Kaper, J.B. Pathogenicity islands and the evolution of microbes. Annu. Rev. Microbiol. 54, 641â679 (2000).
Tettelin, H. et al. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809â1815 (2000).
Kroll, J.S., Wilks, K.E., Farrant, J.L. & Langford, P.R. Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer of chromosomal genes between major human pathogens. Proc. Natl. Acad. Sci. USA 95, 12381â12385 (1998).
Davis, J., Smith, A.L., Hughes, W.R. & Golomb, M. Evolution of an autotransporter: domain shuffling and lateral transfer from pathogenic Haemophilus to Neisseria. J. Bacteriol. 183, 4626â4635 (2001).
Amábile-Cuevas, C.F. & Chicurel, M.E. Bacterial plasmids and gene flux. Cell 70, 189â199 (1992).
Lawrence, J.G. & Ochman, H. Amelioration of bacterial genomes: rates of change and exchange. J. Mol. Evol. 44, 383â397 (1997).
Peterson, J.D., Umayam, L.A., Dickinson, T., Hickey, E.K. & White, O. The Comprehensive Microbial Resource. Nucleic Acids Res. 29, 123â125 (2001).
Finlay, B.B. & Falkow, S. Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61, 136â169 (1997).
Sauer, F.G. et al. Bacterial pili: molecular mechanisms of pathogenesis. Curr. Opin. Microbiol. 3, 65â72 (2000).
Borodovsky, M. & McIninch, J.D. GENMARK: Parallel gene recognition for both DNA strands. Computers Chem. 17, 123â133 (1993).
Borodovsky, M. et al. Detection of new genes in a bacterial genome using Markov models for three gene classes. Nucleic Acids Res. 23, 3554â3562 (1995).
Wang, B. Limitations of compositional approach to identifying horizontally transferred genes. J. Mol. Evol. 53, 244â250 (2001).
Genereux, D.P. & Logsdon, J.M. Jr. Much ado about bacteria-to-vertebrate lateral gene transfer. Trends. Genet. 19, 191â195 (2003).
Karlin, S., Mrázek, J. & Campbell, A.M. Codon usages in different gene classes of the Escherichia coli genome. Mol. Microbiol. 29, 1341â1355 (1998).
Sharp, P.M. & Li, W.H. The codon Adaptation Indexâa measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 15, 1281â1295 (1987).
Hacker, J., Blum-Oehler, G., Mühldorfer, I. & Tschäpe, H. Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol. Microbiol. 23, 1089â1097 (1997).
Pearson, W.R. & Lipman, D.J. Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. USA 85, 2444â2448 (1988).
Thompson, J.D., Higgins, D.G. & Gibson, T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673â4680 (1994).
Saitou, N. & Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406â425 (1987).
Acknowledgements
We thank N. Tsuboi for coding the horizontally transferred gene detection programs; N. Nishinomiya, M. Matsuo and R. Yamaguchi for technical assistance; and K. Ikeo, J.S. Hwang and R. Barrero for their comments and suggestions. T.I. and T.G. were supported in part by grants from the New Energy and Industrial Technology Development Organization and the Ministry of Economy, Technology, and Industry of Japan. T.I., T.G. and H.M. were supported by grants from the Ministry of Education, Sports, Culture, Science and Technology of Japan.
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Supplementary information
Supplementary Fig. 1
Relationship between the total number of examined ORFs and the proportion of HT genes in a genome. (PDF 60 kb)
Supplementary Table 1
Sensitivities and selectivities of HT detection methods. (PDF 2 kb)
Supplementary Table 2
Possible pathogenicity islands detected in this study. (PDF 9 kb)
Supplementary Table 3
Subroles containing frequently transferred genes. (PDF 6 kb)
Supplementary Table 4
Species having an abundance of regulatory function HT genes. (PDF 2 kb)
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Nakamura, Y., Itoh, T., Matsuda, H. et al. Biased biological functions of horizontally transferred genes in prokaryotic genomes. Nat Genet 36, 760â766 (2004). https://doi.org/10.1038/ng1381
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DOI: https://doi.org/10.1038/ng1381
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