A model of directional selection applied to the evolution of drug resistance in HIV-1.

A model of directional selection applied to the evolution of drug resistance in HIV-1. Research Abstract Details 

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A model of directional selection applied to the evolution of drug resistance in HIV-1. Abstract Text:

Cathal Seoighe,Farahnaz Ketwaroo,Visva Pillay,Konrad Scheffler,Natasha Wood,Rodger Duffet,Marketa Zvelebil,Neil Martinson,James McIntyre,Lynn Morris,Winston Hide,

Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

A model of directional selection applied to the evolution of drug resistance in HIV-1. Publishing Authors By Initials

C Seoighe,F Ketwaroo,V Pillay,K Scheffler,N Wood,R Duffet,M Zvelebil,N Martinson,J McIntyre,L Morris,W Hide,

For similar genetic phenomena: variation (genetics) research abstracts see: genetic phenomena: variation (genetics) research

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A model of directional selection applied to the evolution of drug resistance in HIV-1. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular biology and evolution

VOLUME: 24

Page Numbers: 1025-31

Journal Abbreviation: Mol. Biol. Evol.

ISSN: 0737-4038

DAY: 1

MONTH: 02

YEAR: 2007

A model of directional selection applied to the evolution of drug resistance in HIV-1. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8501455

A model of directional selection applied to the evolution of drug resistance in HIV-1. Keywords Mesh Terms:

KEYWORDS: Variation (Genetics)

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: A model of directional selection applied to the evolution of drug resistance in HIV-1. Information

Substance Name: Nevirapine

Registry Number: 129618-40-2

Grant and Affiliation Information for A model of directional selection applied to the evolution of drug resistance in HIV-1.

AFFILIATION: Computational Biology Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, South Africa. cathal.seoighe@uct.ac.za

Country: United States

AGENCY: United States FIC

GRANT: 5D43 TW006993

ACRONYM: TW

MEDLINETA: Mol Biol Evol

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