Relaxed selection and the evolution of RNA virus mucin-like pathogenicity factors
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Mucin-like regions contribute to pathogenicity in a variety of negative-stranded RNA viruses. These regions are characterized by a preponderance of O-linked glycosylation. They evolve exceptionally rapidly yet maintain their function as pathogenicity factors. Two hypotheses have been proposed to explain this evolutionary conundrum of phenotypic stability in the face of extreme genetic divergence: strong positive selection and relaxation of purifying selection. We determined the strength and direction of selection codon by codon across genes containing these regions and found that purifying selection is relaxed over the mucin-like regions relative to the genes in which they are found. This suggests that so long as these regions maintain sufficient O-linked glycosylation, they are free to evolve rapidly without loss of function as pathogenicity factors.
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Approaches estimating the number of sites under strong purifying selection in one region versus another and directly testing for differences in site-specific ! estimates are relevant primarily for comparing selective pressures across regions within a gene.
“Relaxed selection across sites in a gene has also been explored by estimating the number of sites under strong purifying selection in one region versus another (Wertheim and Worobey 2009) and by directly testing for differences in sitespecific !estimates (Pond et al. 2006); however, such approaches are relevant primarily for comparing selective pressures across regions within a gene.”
From RELAX: Detecting Relaxed Selection in a Phylogenetic Framework (2015) · cites this paper as Wertheim and Worobey 2009
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- [11]11. Sanchez, A., S. G. Trappier, B. W. Mahy, C. J. Peters, and S. T. Nichol. 1996. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc. Natl. Acad. Sci. USA 93: 3602-3607.
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RELAX: Detecting Relaxed Selection in a Phylogenetic Framework
Wertheim, J. O., Murrell, B., Smith, M. D., Kosakovsky Pond, S. L., & Scheffler, K. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msu400 · Cited by 778 · see citing works
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- Authors
- Wertheim, J. O., & Worobey, M.
- Affiliations
- University of Arizona (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2009-05
- Volume
- 83
- Issue
- 9
- Pages
- 4690-4694
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2668480
- OpenAlex
- W2170427845
- Cited by
- 20
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 0.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- David and Lucile Packard Foundation
- University of Arizona
- Division of Graduate Education
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- virulence factors, negative-strand RNA viruses, O-glycosylation, relaxed purifying selection, positive selection, codon substitution rates, viral evolution, phenotypic stability
- MeSH terms
- Mucins, RNA Viruses, Selection, Genetic, Reading Frames, Genome, Viral, Evolution, Molecular
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