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Bioinformatics 2005 21(Suppl 3):iii39-iii44; doi:10.1093/bioinformatics/bti1203
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oxfordjournals.org

Within-host evolution of CD8+-TL epitopes encoded by overlapping and non-overlapping reading frames of simian immunodeficiency virus

Austin L. Hughes 1,*, Helen Piontkivska 1, Kendall C. Krebs 2, David H. O'Connor 2 and David I. Watkins 2

1Department of Biological Sciences, University of South Carolina Columbia, SC, USA
2Wisconsin Primate Research Center and Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, WI, USA

*To whom correspondence should be addressed at Department of Biological Sciences, University of South Carolina, Coker Life Sciences Building, 700 Sumter Street, Columbia SC 29208, USA.

Summary: In order to understand the impact of overlapping reading frames on natural selection by host CD8+ T lymphocytes (CD8+-TL), we analyzed the pattern of nucleotide substitution in simian immunodeficiency virus (SIV) genomes sampled from populations at time of death in 35 rhesus monkeys. Both the mean number of nonsynonymous nucleotide substitutions per nonsynonymous site (dN) and the mean number of synonymous nucleotide substitutions per synonymous site (dS) were elevated in overlap regions in comparison to non-overlap regions. Mean dN exceeded mean dS in CD8+-TL epitopes restricted by the host's class I major histocompatibility complex molecules. This pattern, which is indicative of positive Darwinian selection favoring amino acid changes in these epitopes, was seen in both overlap and non-overlap regions; but mean dN was particularly elevated in restricted CD8+-TL epitopes encoded in overlap regions. Amino acid changes from the inoculum were defined as parallel if the same amino acid change occurred at the same site independently in two or more monkeys, and a surprisingly high proportion (71.9%) of observed amino acid changes throughout the SIV genome occurred in parallel in different monkeys. The proportion of parallel changes in restricted epitopes encoded by overlapping reading frames was still higher (80%), supporting the hypothesis that the interaction of positive selection and overlapping reading frames enhances the probability of convergent or parallel amino acid change.

Contact: austin{at}biol.sc.edu

Received on May 10, 2005; accepted on August 16, 2005

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