Quantifying selection against synonymous mutations in HIV-1 env evolution

Zanini, Fabio and Neher, Richard A.. (2013) Quantifying selection against synonymous mutations in HIV-1 env evolution. Journal of virology, 87 (21). pp. 11843-11850.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/53990/

Downloads: Statistics Overview


Intrapatient evolution of human immunodeficiency virus type 1 (HIV-1) is driven by the adaptive immune system resulting in rapid change of HIV-1 proteins. When cytotoxic CD8(+) T cells or neutralizing antibodies target a new epitope, the virus often escapes via nonsynonymous mutations that impair recognition. Synonymous mutations do not affect this interplay and are often assumed to be neutral. We test this assumption by tracking synonymous mutations in longitudinal intrapatient data from the C2-V5 part of the env gene. We find that most synonymous variants are lost even though they often reach high frequencies in the viral population, suggesting a cost to the virus. Using published data from SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) assays, we find that synonymous mutations that disrupt base pairs in RNA stems flanking the variable loops of gp120 are more likely to be lost than other synonymous changes: these RNA hairpins might be important for HIV-1. Computational modeling indicates that, to be consistent with the data, a large fraction of synonymous mutations in this genomic region need to be deleterious with a cost on the order of 0.002 per day. This weak selection against synonymous substitutions does not result in a strong pattern of conservation in cross-sectional data but slows down the rate of evolution considerably. Our findings are consistent with the notion that large-scale patterns of RNA structure are functionally relevant, whereas the precise base pairing pattern is not.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Computational Modeling of Biological Processes (Neher)
UniBasel Contributors:Neher, Richard
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Microbiology
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:18 Sep 2019 07:29
Deposited On:30 Nov 2017 12:49

Repository Staff Only: item control page