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Journal of Virology, November 2006, p. 11124-11140, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01076-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Recombination and Selection in the Evolution of Picornaviruses and Other Mammalian Positive-Stranded RNA Viruses{triangledown}

Peter Simmonds*

Virus Evolution Group, Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom

Received 25 May 2006/ Accepted 29 August 2006

Picornaviridae are a large virus family causing widespread, often pathogenic infections in humans and other mammals. Picornaviruses are genetically and antigenically highly diverse, with evidence for complex evolutionary histories in which recombination plays a major part. To investigate the nature of recombination and selection processes underlying the evolution of serotypes within different picornavirus genera, large-scale analysis of recombination frequencies and sites, segregation by serotype within each genus, and sequence selection and composition was performed, and results were compared with those for other nonenveloped positive-stranded viruses (astroviruses and human noroviruses) and with flavivirus and alphavirus control groups. Enteroviruses, aphthoviruses, and teschoviruses showed phylogenetic segregation by serotype only in the structural region; lack of segregation elsewhere was attributable to extensive interserotype recombination. Nonsegregating viruses also showed several characteristic sequence divergence and composition differences between genome regions that were absent from segregating virus control groups, such as much greater amino acid sequence divergence in the structural region, markedly elevated ratios of nonsynonymous-to-synonymous substitutions, and differences in codon usage. These properties were shared with other picornavirus genera, such as the parechoviruses and erboviruses. The nonenveloped astroviruses and noroviruses similarly showed high frequencies of recombination, evidence for positive selection, and differential codon use in the capsid region, implying similar underlying evolutionary mechanisms and pressures driving serotype differentiation. This process was distinct from more-recent sequence evolution generating diversity within picornavirus serotypes, in which neutral or purifying selection was prominent. Overall, this study identifies common themes in the diversification process generating picornavirus serotypes that contribute to understanding of their evolution and pathogenicity.

* Mailing address: Virus Evolution Group, Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom. Phone: 44 0131 650 7927. Fax: 44 0131 650 6511. E-mail: Peter.Simmonds{at}ed.ac.uk.

{triangledown} Published ahead of print on 6 September 2006.

Journal of Virology, November 2006, p. 11124-11140, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01076-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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