Adaptive evolution of interferon-γ in Glire lineage and evidence for a recent selective sweep in Mus. m. domesticus

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Abstract

Interferon-γ plays a key role in the immune response against intracellular pathogens. Its gene is located inside a cluster of cytokines from the interleukin-10 family. A comparison of the coding sequences in the mammalian Glire lineage indicates a possible action of positive Darwinian selection promoting rapid amino-acid changes in the branch leading to murine rodents represented by Mus and Rattus. Looking at genomic diversity of this gene inside the genus Mus, we could propose that a recent selective sweep has affected M. m. domesticus, this subspecies harbouring predominantly a single Ifng haplotype that differs from that of the other subspecies by a unique amino-acid difference in a key position of the molecule. The sweep seems to have affected a region of at most 50 kb as recombinants could be found at flanking conserved non-coding sequences. Functional differences were clearly apparent in cis-regulation of Ifng transcription between the domesticus and the musculustype haplotypes. As the presence of the musculus haplotype in a predominantly domesticus background seems to promote susceptibility to chronic infection by Theiler's virus, these findings open interesting avenues for documenting immune system gene co-evolution.

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