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Phylogenetic analysis of population-based and deep sequencing data to identify coevolving sites in the nef gene of HIV-1.

https://arctichealth.org/en/permalink/ahliterature147008
Source
Mol Biol Evol. 2010 Apr;27(4):819-32
Publication Type
Article
Date
Apr-2010
Author
Art F Y Poon
Luke C Swenson
Winnie W Y Dong
Wenjie Deng
Sergei L Kosakovsky Pond
Zabrina L Brumme
James I Mullins
Douglas D Richman
P Richard Harrigan
Simon D W Frost
Author Affiliation
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada. apoon@cfenet.ubc.ca
Source
Mol Biol Evol. 2010 Apr;27(4):819-32
Date
Apr-2010
Language
English
Publication Type
Article
Keywords
Amino Acid Sequence
British Columbia
Cohort Studies
Evolution, Molecular
HIV Infections - virology
HIV-1 - genetics
Humans
Molecular Sequence Data
Phylogeny
Sequence Alignment
Sequence Analysis, RNA - methods
nef Gene Products, Human Immunodeficiency Virus - chemistry - genetics
Abstract
Rapidly evolving viruses such as HIV-1 display extensive sequence variation in response to host-specific selection, while simultaneously maintaining functions that are critical to replication and infectivity. This apparent conflict between diversifying and purifying selection may be resolved by an abundance of epistatic interactions such that the same functional requirements can be met by highly divergent sequences. We investigate this hypothesis by conducting an extensive characterization of sequence variation in the HIV-1 nef gene that encodes a highly variable multifunctional protein. Population-based sequences were obtained from 686 patients enrolled in the HOMER cohort in British Columbia, Canada, from which the distribution of nonsynonymous substitutions in the phylogeny was reconstructed by maximum likelihood. We used a phylogenetic comparative method on these data to identify putative epistatic interactions between residues. Two interactions (Y120/Q125 and N157/S169) were chosen to further investigate within-host evolution using HIV-1 RNA extractions from plasma samples from eight patients. Clonal sequencing confirmed strong linkage between polymorphisms at these sites in every case. We used massively parallel pyrosequencing (MPP) to reconstruct within-host evolution in these patients. Experimental error associated with MPP was quantified by performing replicates at two different stages of the protocol, which were pooled prior to analysis to reduce this source of variation. Phylogenetic reconstruction from these data revealed correlated substitutions at Y120/Q125 or N157/S169 repeated across multiple lineages in every host, indicating convergent within-host evolution shaped by epistatic interactions.
Notes
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PubMed ID
19955476 View in PubMed
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