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Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes
The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1–V5) of the surface envelope glycoprotein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change in these regions. However, the rate an...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642732/ https://www.ncbi.nlm.nih.gov/pubmed/31341641 http://dx.doi.org/10.1093/ve/vez022 |
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author | Palmer, John Poon, Art F Y |
author_facet | Palmer, John Poon, Art F Y |
author_sort | Palmer, John |
collection | PubMed |
description | The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1–V5) of the surface envelope glycoprotein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change in these regions. However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences. Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M. We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis. We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries). By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection. Rate estimates ranged from [Formula: see text] to [Formula: see text] indels/nt/year and varied significantly among variable regions and subtypes. Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference. We also found that V1, V2, and V4 tended to accumulate significantly longer indels. Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions. These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1. |
format | Online Article Text |
id | pubmed-6642732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-66427322019-07-24 Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes Palmer, John Poon, Art F Y Virus Evol Research Article The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1–V5) of the surface envelope glycoprotein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change in these regions. However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences. Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M. We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis. We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries). By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection. Rate estimates ranged from [Formula: see text] to [Formula: see text] indels/nt/year and varied significantly among variable regions and subtypes. Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference. We also found that V1, V2, and V4 tended to accumulate significantly longer indels. Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions. These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1. Oxford University Press 2019-07-21 /pmc/articles/PMC6642732/ /pubmed/31341641 http://dx.doi.org/10.1093/ve/vez022 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article Palmer, John Poon, Art F Y Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes |
title | Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes |
title_full | Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes |
title_fullStr | Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes |
title_full_unstemmed | Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes |
title_short | Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes |
title_sort | phylogenetic measures of indel rate variation among the hiv-1 group m subtypes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642732/ https://www.ncbi.nlm.nih.gov/pubmed/31341641 http://dx.doi.org/10.1093/ve/vez022 |
work_keys_str_mv | AT palmerjohn phylogeneticmeasuresofindelratevariationamongthehiv1groupmsubtypes AT poonartfy phylogeneticmeasuresofindelratevariationamongthehiv1groupmsubtypes |