Recombination Rate and Selection Strength in HIV Intra-patient Evolution
Abstract
The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Yet, little is known about the distribution of selection differentials between individual viruses and the impact of single polymorphisms on viral fitness. Here, we estimate the rate of recombination and the distribution of selection coefficients from time series sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be ρ = 1.4±0.6×10–5 recombinations per site and generation. Furthermore, we provide evidence that the selection coefficients of atmore »
- Authors:
-
- Univ. of California, Santa Barbara, CA (United States)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Science Foundation (NSF); USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1627196
- Grant/Contract Number:
- AC52-06NA25396; PHY05-51164; X9R8
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS Computational Biology (Online)
- Additional Journal Information:
- Journal Name: PLoS Computational Biology (Online); Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 1553-7358
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 97 MATHEMATICS AND COMPUTING; Biochemistry & Molecular Biology; Mathematical & Computational Biology
Citation Formats
Neher, Richard A., and Leitner, Thomas. Recombination Rate and Selection Strength in HIV Intra-patient Evolution. United States: N. p., 2010.
Web. doi:10.1371/journal.pcbi.1000660.
Neher, Richard A., & Leitner, Thomas. Recombination Rate and Selection Strength in HIV Intra-patient Evolution. United States. https://doi.org/10.1371/journal.pcbi.1000660
Neher, Richard A., and Leitner, Thomas. Fri .
"Recombination Rate and Selection Strength in HIV Intra-patient Evolution". United States. https://doi.org/10.1371/journal.pcbi.1000660. https://www.osti.gov/servlets/purl/1627196.
@article{osti_1627196,
title = {Recombination Rate and Selection Strength in HIV Intra-patient Evolution},
author = {Neher, Richard A. and Leitner, Thomas},
abstractNote = {The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Yet, little is known about the distribution of selection differentials between individual viruses and the impact of single polymorphisms on viral fitness. Here, we estimate the rate of recombination and the distribution of selection coefficients from time series sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be ρ = 1.4±0.6×10–5 recombinations per site and generation. Furthermore, we provide evidence that the selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible as soon as data with higher time resolution and greater sample sizes are available.},
doi = {10.1371/journal.pcbi.1000660},
journal = {PLoS Computational Biology (Online)},
number = 1,
volume = 6,
place = {United States},
year = {Fri Jan 29 00:00:00 EST 2010},
month = {Fri Jan 29 00:00:00 EST 2010}
}
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Selection in ContextSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AF016760, AF016761, AF016762, AF016763, AF016764, AF016765, AF016766, AF016767, AF016768, AF016769, AF016770, AF016771, AF016772, AF016773, AF016774, AF016775, AF016776, AF016777, AF016778, AF016779, AF016780, AF016781, AF016782, AF016783, AF016784, AF016785, AF016786, AF016787, AF016788, AF016789, AF016790, AF016791, AF016792, AF016793, AF016794, AF016795, AF016796, AF016797, AF016798, AF016799, AF016800, AF016801, AF016802, AF016803, AF016804, AF016805, AF016806, AF016807, AF016808, AF016809, AF016810, AF016811, AF016812, AF016813, AF016814, AF016815, AF016816, AF016817, AF016818, AF016819, AF016820, AF016821, AF016822, AF016823, AF016824, AF016825 and AF089109, AF089708.
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