Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs
HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The ra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/9/1689 |
| _version_ | 1827681084273328128 |
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| author | Arshan Nasir Mira Dimitrijevic Ethan Romero-Severson Thomas Leitner |
| author_facet | Arshan Nasir Mira Dimitrijevic Ethan Romero-Severson Thomas Leitner |
| author_sort | Arshan Nasir |
| collection | DOAJ |
| description | HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10<sup>−3</sup> to 4.72 × 10<sup>−3</sup> in <i>env</i> and 2.3-fold from 0.95 × 10<sup>−3</sup> to 2.18 × 10<sup>−3</sup> substitutions site<sup>−1</sup> year<sup>−1</sup> in <i>pol</i>. Within the subtype, 3-fold rate variation was observed in <i>env</i> in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages. |
| first_indexed | 2024-03-10T07:08:20Z |
| format | Article |
| id | doaj.art-18cb930cb3ba4758b8e1366eea875a29 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T07:08:20Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj.art-18cb930cb3ba4758b8e1366eea875a292023-11-22T15:36:28ZengMDPI AGViruses1999-49152021-08-01139168910.3390/v13091689Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFsArshan Nasir0Mira Dimitrijevic1Ethan Romero-Severson2Thomas Leitner3Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USATheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USATheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USATheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USAHIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10<sup>−3</sup> to 4.72 × 10<sup>−3</sup> in <i>env</i> and 2.3-fold from 0.95 × 10<sup>−3</sup> to 2.18 × 10<sup>−3</sup> substitutions site<sup>−1</sup> year<sup>−1</sup> in <i>pol</i>. Within the subtype, 3-fold rate variation was observed in <i>env</i> in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages.https://www.mdpi.com/1999-4915/13/9/1689HIV-1phylogeneticsevolutionary ratesubtypes |
| spellingShingle | Arshan Nasir Mira Dimitrijevic Ethan Romero-Severson Thomas Leitner Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs Viruses HIV-1 phylogenetics evolutionary rate subtypes |
| title | Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs |
| title_full | Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs |
| title_fullStr | Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs |
| title_full_unstemmed | Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs |
| title_short | Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs |
| title_sort | large evolutionary rate heterogeneity among and within hiv 1 subtypes and crfs |
| topic | HIV-1 phylogenetics evolutionary rate subtypes |
| url | https://www.mdpi.com/1999-4915/13/9/1689 |
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