Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.
The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic dri...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2006
|
| _version_ | 1826294814735335424 |
|---|---|
| author | Edwards, C Holmes, E Pybus, O Wilson, D Viscidi, R Abrams, E Phillips, R Drummond, A |
| author_facet | Edwards, C Holmes, E Pybus, O Wilson, D Viscidi, R Abrams, E Phillips, R Drummond, A |
| author_sort | Edwards, C |
| collection | OXFORD |
| description | The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation. |
| first_indexed | 2024-03-07T03:51:29Z |
| format | Journal article |
| id | oxford-uuid:c16b49f4-0b5e-4e0b-83d5-431a7ab8c6e5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:51:29Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:c16b49f4-0b5e-4e0b-83d5-431a7ab8c6e52022-03-27T06:01:25ZEvolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c16b49f4-0b5e-4e0b-83d5-431a7ab8c6e5EnglishSymplectic Elements at Oxford2006Edwards, CHolmes, EPybus, OWilson, DViscidi, RAbrams, EPhillips, RDrummond, AThe evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation. |
| spellingShingle | Edwards, C Holmes, E Pybus, O Wilson, D Viscidi, R Abrams, E Phillips, R Drummond, A Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection. |
| title | Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection. |
| title_full | Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection. |
| title_fullStr | Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection. |
| title_full_unstemmed | Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection. |
| title_short | Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection. |
| title_sort | evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection |
| work_keys_str_mv | AT edwardsc evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT holmese evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT pybuso evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT wilsond evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT viscidir evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT abramse evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT phillipsr evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection AT drummonda evolutionofthehumanimmunodeficiencyvirusenvelopegeneisdominatedbypurifyingselection |