Journal of Molecular Evolution

, Volume 42, Issue 5, pp 537–542

Phylogenetic analysis of the isopenicillin-N-synthetase horizontal gene transfer

  • Celia Buades
  • Andrés Moya


A phylogenetic study of the isopenicillin-N-synthetase (IPNS) gene sequence from prokaryotic and lower eukaryotic producers of β-lactam antibiotics by means of a maximum-likelihood approach has been carried out. After performing an extensive search, rather than invoking a global molecular clock, the results obtained are best explained by a model with three rates of evolution. Grouped in decreasing order, these correspond toA. nidulans and then to the rest of the eukaryotes and prokaryotes, respectively. The estimated branching date between prokaryotic and fungal IPNS sequences (852 ±106 MY) strongly supports the hypothesis that the IPNS gene was horizontally transferred from bacterial β-lactam producers to filamentous fungi.

Key words

Horizontal gene transfer β-lactam producers Maximum likelihood Molecular clock 


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  1. Akaike H (1974) A new look at the statistical model identification. Inst Electrical Electronics IEEE Trans Autom Contr AC-19:716–723Google Scholar
  2. Cohen G, Shiffman D, Mavarech M, Aharonowitz Y (1990) Microbial isopenicillin N synthase genes: structure, function, diversity and evolution. Trends Biotechnol 8:105–111CrossRefPubMedGoogle Scholar
  3. Coque JJR, Martín JF, Calzada JG, Liras P (1991a) The cephamycin biosynthetic genepcbAB, encoding a large multidomain peptide synthetase, andpcbC ofNocardia lactamdurans are clustered together in an organization different from the same genes inA. chrysogenum andP. chrysogenum. Mol Microbial 5:1125–1133Google Scholar
  4. Coque JJR, Liras P, Laiz L, Martín IF (1991b) A gene encoding lisyne 6-aminotransferase, which forms the β-lactam precursor α-aminoadipic acid, is located in the cluster of cephamycin biosynthetic genes inNocardia lactamdurans. J Bacteriol 173:6258–6264Google Scholar
  5. Dyer BD, Obar RA (1994) Tracing the history of eukaryotic cells. Columbia University Press, New YorkGoogle Scholar
  6. Elander RP (1983) Strain improvement and preservation of β-lactam producing microorganisms. In: Demain AL, Solomon NA (eds) Antibiotic containing the β-lactam structure I. Springer, Berlin, p 97Google Scholar
  7. Felsenstein J (1990) PHYLIP manual. Version 3.3. University of California Press, BerkeleyGoogle Scholar
  8. Fitch WM (1970) Distinguishing homologous from analogous proteins. Syst Zool 19:99–113PubMedGoogle Scholar
  9. Gray GS, Fitch WM (1983) Evolution of antibiotic resistance genes: the DNA sequence of a kanamycin resistance gene fromStaphylococcus aureus. Mol Biol Evol 1:57–66PubMedGoogle Scholar
  10. Hasegawa M, Kishino H, Yano T (1985) Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol 22:160–174PubMedGoogle Scholar
  11. Higgins DG, Sharp PM (1989) Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biol Sci 5:151–153PubMedGoogle Scholar
  12. Hori H, Osawa S (1987) Origin and evolution of organisms as deduced from 5S ribosomal RNA sequences. Mol Biol Evol 4:445–472PubMedGoogle Scholar
  13. Jensen SE (1986) Biosynthesis of cephalosporins. Crit Rev Biotechnol 3:277–301Google Scholar
  14. Kidwell M (1993) Lateral transfer in natural populations of eukaryotes. Annu Rev Genet 27:235–256CrossRefPubMedGoogle Scholar
  15. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  16. Kishino H, Hasegawa M (1990) Converting distances to time: an application to human evolution. Methods Enzymol 183:550–570PubMedGoogle Scholar
  17. Landan G, Cohen G, Aharonowitz Y, Shuali Y, Graur D, Shiffman D (1990) Evolution of isopenicillin N synthase may have involved horizontal gene transfer. Mol Biol Evol 7:399–406PubMedGoogle Scholar
  18. Lawrence JG, Hard DL (1992) Inference of horizontal genetic transfer from molecular data: an approach using bootstrap. Genetics 131:753–760PubMedGoogle Scholar
  19. Miller JR, Ingolia TD (1989) Cloning and characterization of betalactam biosynthetic genes. Mol Microbiol 3:689–695PubMedGoogle Scholar
  20. Peñalva MA, Moya A, Dopazo J, Ramón D (1990) Sequences of isopenicillin N syntherase genes suggest horizontal gene transfer from prokaryotes to eukaryotes. Proc R Soc Lond [Biol] 241:161–169Google Scholar
  21. Ram′n D, Carramolino L, Patiño C, Sánchez F, Peñalva MA (1987) Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the β-lactam ring inAspergillus nidulans. Gene 57:171–181Google Scholar
  22. Roach PL, Clifton IJ, Füilöp V, Harlos K, Barton GJ, Hajdu J, Anderson I, Schofield CJ, Baldwin JE. (1995) Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature 375:700–704CrossRefPubMedGoogle Scholar
  23. Smith DJ, Burnham MKR, Bull JH, Hodgson JE, Ward JM, Browne P, Brown L, Barton B, Earl AJ, Turner G (1990a) β-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes. EMBO J 9:741–747Google Scholar
  24. Smith DJ, Burnham MKR, Edwards J, Earl AJ, Turner G (1990b) Cloning and heterologous expression of the penicillin biosynthetic gene cluster fromP. chrysogenum. BioTechnology 8:39–41Google Scholar
  25. Smith DJ, Earl AJ, Turner G (1990c) The multifunctional peptide synthetase performing the first step of penicillin biosynthesis inP. chrysogenum is a 421.073 dalton protein similar toBacillus brevis peptide antibiotic synthetases. EMBO J 9:2743–2750Google Scholar
  26. Smith MW, Feng DF, Doolittle RF (1992) Evolution by adquisition: the case for horizontal gene transfers. Trends Biochem Sci 17:489–493CrossRefPubMedGoogle Scholar
  27. Syvanen M (1994) Horizontal gene transfer: evidence and possible consequences. Annu Rev Genet 28:237–261PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc 1996

Authors and Affiliations

  • Celia Buades
    • 1
  • Andrés Moya
    • 1
  1. 1.Departamento de Genética, Facultad de Biología and Servicio de BioinfonnáticaUniversidad de ValenciaBurjassot, ValenciaSpain

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