Modeling HIV-1 drug resistance as episodic directional selection
Date
2011-05
Authors
Murrell, Ben
De Oliveira, Tulio
Seebregts, Chris
Pond, Sergei L. Kosakovsky
Scheffler, Konrad
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS Computational Biology
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. Whilemethods 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 (MEDSand) 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.
Description
The original publication is available at www.ploscompbiol.org
Keywords
HIV infections, Drug resistance
Citation
Murrell, B. et al. 2012. Modeling HIV-1 drug resistance as episodic directional selection. PLoS Computational Biology, 8(5):1-10. doi:10.1371/journal.pcbi.1002507.