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Open Access Research article

Attenuation of virulence in an apicomplexan hemoparasite results in reduced genome diversity at the population level

Audrey OT Lau1*, Ananth Kalyanaraman2, Ignacio Echaide3, Guy H Palmer1, Russell Bock4, Monica J Pedroni1, Meenakshi Rameshkumar2, Mariano B Ferreira3, Taryn I Fletcher45 and Terry F McElwain1

Author Affiliations

1 Programs in Genomics and Vector-borne Diseases, Department of Veterinary Microbiology & Pathology and Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA

2 School of Electrical Engineering and Computer Science, Washington State University, Pullman WA 99164-2752, USA

3 Instituto Nacional Tecnologia Agropecuaria, 2300 Rafaela, Santa Fe, Argentina

4 Tick Fever Centre, Biosecurity, Department of Primary Industries and Fisheries, 280 Grindle Road, Wacol, Qld. 4076, Australia

5 Department of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK

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BMC Genomics 2011, 12:410  doi:10.1186/1471-2164-12-410

Published: 12 August 2011

Abstract

Background

Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background.

Results

Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains.

Conclusions

This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus.