Long-term balancing selection at the West Nile virus resistance gene, Oas1b, maintains transspecific polymorphisms in the house mouse

William Ferguson, Shira Dvora, Juliana Gallo, Annie Orth, Stephane Boissinot

    Research output: Contribution to journalArticle

    Abstract

    Oligoadenylate synthetases (OASs) are interferon-inducible enzymes that participate in the first line of defense against a wide range of viral infection. Recent studies have determined that Oas1b, a member of the OAS gene family in the house mouse (Mus musculus), provides specific protection against flavivirus infection (e.g., West Nile virus, dengue fever virus, and yellow fever virus). We characterized the nucleotide sequence variation in coding and noncoding regions of the Oas1b gene for a large number of wild-derived strains of M. musculus and related species. Our sequence analyses determined that this gene is one of the most polymorphic genes ever described in any mammal. The level of variation in noncoding regions of Oas1b is an order of magnitude higher than the level reported for other regions of the mouse genome and is significantly different from the level of intraspecific variation expected under neutrality. Furthermore, a phylogenetic analysis of intronic sequences demonstrated that Oas1b alleles are ancient and that their divergence predates several speciation events, resulting in transspecific polymorphisms. The amino acid sequence of Oas1b is also extremely variable, with 1 out of 7 amino acid positions being polymorphic within M. musculus. Oas1b alleles are comparatively more divergent at synonymous positions than most autosomal genes and the ratio of nonsynonymous to synonymous substitution is remarkably high, suggesting that positive selection has been acting on Oas1b. The ancestry of Oas1b polymorphisms and the high level of amino acid polymorphisms strongly suggest that the allelic variation at Oas1b has been maintained in mouse populations by long-term balancing selection.

    Original languageEnglish (US)
    Pages (from-to)1609-1618
    Number of pages10
    JournalMolecular Biology and Evolution
    Volume25
    Issue number8
    DOIs
    StatePublished - Aug 1 2008

    Fingerprint

    West Nile virus
    Mus musculus
    polymorphism
    genetic polymorphism
    gene
    amino acid
    Genes
    ligases
    genes
    Ligases
    allele
    virus
    Yellow fever virus
    Sequence Analysis
    yellow fever
    dengue fever
    Flavivirus Infections
    alleles
    Flavivirus
    Alleles

    Keywords

    • Balancing selection
    • Flavivirus
    • Mus musculus
    • Oas1b
    • West Nile virus

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Molecular Biology
    • Genetics

    Cite this

    Long-term balancing selection at the West Nile virus resistance gene, Oas1b, maintains transspecific polymorphisms in the house mouse. / Ferguson, William; Dvora, Shira; Gallo, Juliana; Orth, Annie; Boissinot, Stephane.

    In: Molecular Biology and Evolution, Vol. 25, No. 8, 01.08.2008, p. 1609-1618.

    Research output: Contribution to journalArticle

    Ferguson, William ; Dvora, Shira ; Gallo, Juliana ; Orth, Annie ; Boissinot, Stephane. / Long-term balancing selection at the West Nile virus resistance gene, Oas1b, maintains transspecific polymorphisms in the house mouse. In: Molecular Biology and Evolution. 2008 ; Vol. 25, No. 8. pp. 1609-1618.
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