Format

Send to

Choose Destination
PLoS Comput Biol. 2012;8(5):e1002507. doi: 10.1371/journal.pcbi.1002507. Epub 2012 May 10.

Modeling HIV-1 drug resistance as episodic directional selection.

Author information

1
Biomedical Informatics Research Division, eHealth Research and Innovation Platform, Medical Research Council, Tygerberg, South Africa.

Abstract

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

PMID:
22589711
PMCID:
PMC3349733
DOI:
10.1371/journal.pcbi.1002507
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center