Genetic mechanisms of bacterial antigenic variation

H. S. Seifert, M. So

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations


The studies described above indicate that procaryotes have evolved a variety of mechanisms to vary their surface coats. N. gonorrhoeae primarily uses DNA transformation to effect pilus antigenic variation at the recombinational level. It also uses recombination (and perhaps also DNA transformation) to bring about P.II antigenic variation at the translational level. Finally, Borrelia organisms have evolved a plasmid recombination system to undergo VMP antigenic variation. To place procaryotic antigenic variation into proper perspective, we end this review with a brief consideration of the host immune system. Mammals have also evolved what could be considered an antigenic variation system, i.e., the generation of antibodies with different antigen-binding specificities. The arrangement of multiple copies of V, D, and J gene segments in the mammalian genome is reminiscent of the arrangement of silent pilin gene segments in the gonococcal chromosome. However, unlike pilin, P.II, and VMP expression, the generation of a functional expressing immunoglobulin gene does not involve expression sites. Instead, a complete immunoglobulin gene is created by recombinational joining of various gene segments, with concomitant deletion of intervening sequences. A system that appears to resemble the gonococcal pilin mechanism has been described for chicken immunoglobulin light chains. The light chain variants all are derived from a unique V-J rearrangement, with diversification occurring by gene conversion from other V gene copies to this single expressed gene within the Bursa of Fabricius. Four main processes appear to be responsible for the generation of antibody diversity in mammalian cells. The first, known as 'combinational diversity', is the joining of V and J gene segments in various combinations. Diversity could also be generated by imprecise joining at V-J, V-D, and D-J junctions. In addition, joining of the V(H)-D and D-J(H) segments could lead to insertion of one to several nucleotides at these junctions. Finally, sequence changes could occur in immunoglobulin gene segments by somatic mutation. Whether these four processes also contribute to antigenic variation in procaryotic systems is not known at present. Since both the procaryotic and eucaryotic systems operate at the recombinational level, it is possible that the first three processes which contribute to immunoglobulin diversity also play a role in procaryotic antigenic variation. As for somatic mutations, it is clear that antigenic drift contributes significantly to the generation of hemagglutinin and neuraminidase variants of the flu virus. It is therefore likely that this process also contributes to sequence variability of the pilin, P.II, and VMP genes. In addition, gene conversion is thought to contribute to the generation of somatic mutation in immunoglobulin genes. In summary, it is interesting to note that the systems of antigenic variation and immunoglobulin diversification have evolved in a similar and complementary fashion, with DNA recombination playing a central mechanistic role. It is highly likely that the two systems developed together, with each providing the evolutionary pressure needed by the other. Finally, the examples of antigenic variation covered in this review illustrate the fascinating and diverse ways microbes have found to regulate and alter gene expression.

Original languageEnglish (US)
Pages (from-to)327-336
Number of pages10
JournalMicrobiological Reviews
Issue number3
StatePublished - 1988

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology


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