Resolving genetic linkage reveals patterns of selection in HIV-1 evolution Article Swipe
Muhammad Saqib Sohail
,
Raymond H. Y. Louie
,
Matthew R. McKay
,
John P. Barton
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1101/711861
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1101/711861
Identifying the genetic drivers of adaptation is a necessary step in understanding the dynamics of rapidly evolving pathogens and cancer. However, signals of selection are obscured by the complex, stochastic nature of evolution. Pervasive effects of genetic linkage, including genetic hitchhiking and clonal interference between beneficial mutants, challenge our ability to distinguish the selective effect of individual mutations. Here we describe a method to infer selection from genetic time series data that systematically resolves the confounding effects of genetic linkage. We applied our method to investigate patterns of selection in intrahost human immunodeficiency virus (HIV)-1 evolution, including a case in an individual who develops broadly neutralizing antibodies (bnAbs). Most variants that arise are observed to have negligible effects on inferred selection at other sites, but a small minority of highly influential variants have strong and far-reaching effects. In particular, we found that accounting for linkage is crucial for estimating selection due to clonal interference between escape mutants and other variants that sweep rapidly through the population. We observed only modest selection for antibody escape, in contrast with strong selection for escape from CD8+ T cell responses. Weak selection for escape from antibody responses may facilitate bnAb development by diversifying the viral population. Our results provide a quantitative description of the evolution of HIV-1 in response to host immunity, including selection on the viral population that accompanies bnAb development. More broadly, our analysis argues for the importance of resolving linkage effects in studies of natural selection.
Related Topics
Concepts
Biology
Selection (genetic algorithm)
Population
Evolutionary biology
Negative selection
Viral evolution
Natural selection
Background selection
Genetics
Adaptation (eye)
Gene
Allele
Genome
Computer science
Demography
Neuroscience
Artificial intelligence
Sociology
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/711861
- https://www.biorxiv.org/content/biorxiv/early/2019/08/06/711861.full.pdf
- OA Status
- green
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2963201839
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2963201839Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/711861Digital Object Identifier
- Title
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Resolving genetic linkage reveals patterns of selection in HIV-1 evolutionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2019Year of publication
- Publication date
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2019-07-23Full publication date if available
- Authors
-
Muhammad Saqib Sohail, Raymond H. Y. Louie, Matthew R. McKay, John P. BartonList of authors in order
- Landing page
-
https://doi.org/10.1101/711861Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2019/08/06/711861.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2019/08/06/711861.full.pdfDirect OA link when available
- Concepts
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Biology, Selection (genetic algorithm), Population, Evolutionary biology, Negative selection, Viral evolution, Natural selection, Background selection, Genetics, Adaptation (eye), Gene, Allele, Genome, Computer science, Demography, Neuroscience, Artificial intelligence, SociologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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46Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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