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Infection and Immunity, August 2009, p. 3181-3187, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00348-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Generation of Antigenic Variants via Gene Conversion: Evidence for Recombination Fitness Selection at the Locus Level in Anaplasma marginale{triangledown}

James E. Futse, Kelly A. Brayton, Seth D. Nydam, and Guy H. Palmer*

Program in Vector-borne Diseases, Department of Veterinary Microbiology and Pathology, and School for Global Animal Health, Washington State University, Pullman, Washington 99164

Received 25 March 2009/ Returned for modification 30 April 2009/ Accepted 26 May 2009

Multiple bacterial and protozoal pathogens utilize gene conversion to generate antigenically variant surface proteins to evade immune clearance and establish persistent infection. Both the donor alleles that encode the variants following recombination into an expression site and the donor loci themselves are under evolutionary selection: the alleles that encode variants that are sufficiently antigenically unique yet retain growth fitness and the loci that allow efficient recombination. We examined allelic usage in generating Anaplasma marginale variants during in vivo infection in the mammalian reservoir host and identified preferential usage of specific alleles in the absence of immune selective pressure, consistent with certain individual alleles having a fitness advantage for in vivo growth. In contrast, the loci themselves appear to have been essentially equally selected for donor function in gene conversion with no significant effect of locus position relative to the expression site or origin of replication. This pattern of preferential allelic usage but lack of locus effect was observed independently for Msp2 and Msp3 variants, both generated by gene conversion. Furthermore, there was no locus effect observed when a single locus contained both msp2 and msp3 alleles in a tail-to-tail orientation flanked by a repeat. These experimental results support the hypothesis that predominance of specific variants reflects in vivo fitness as determined by the encoding allele, independent of locus structure and chromosomal position. Identification of highly fit variants provides targets for vaccines that will prevent the high-level bacteremia associated with acute disease.

* Corresponding author. Mailing address: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040. Phone: (509) 335-6033. Fax: (509) 335-8529. E-mail: gpalmer{at}vetmed.wsu.edu

{triangledown} Published ahead of print on 1 June 2009.

Editor: R. P. Morrison

Infection and Immunity, August 2009, p. 3181-3187, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00348-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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