Adaptive evolution of interferon-gamma in Glire lineage and evidence for a recent selective sweep in Mus. m. domesticus.
Interferon-gamma 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 musculus-type 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.
Levi-Acobas
F
F
Département de Virologie, Institut Pasteur, Paris, France.
Mars
L T
LT
Orth
A
A
Bureau
J-F
JF
Bonhomme
F
F
D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics* / Q000276:immunology; D000818:Animals; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D011110:Polymorphism, Genetic
D007371:Interferon-gamma