Year: 2012
Type: article
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.
Source: PLoS Computational Biology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: G1781340182, G1812340134, Identifying Selection Pressures on Viral Genomes, Africa Centre for Health and Population Studies: Core Support, G33819333, Primary Infection Resource Consortium (PIRC), G5466456334, BIOMATHEMATICAL ANALYSIS OF VIRAL DYNAMICS AND EVOLUTION, G5918387183, G6226294872, G666894910, Determinants of HIV Transmission, G9000031394, G9000062723, G9000250648
OpenAlex ID: W2121979869