Comprehensive sequence analysis of the human IL23A gene defines new variation content and high rate of evolutionary conservation.
A newly described heterodimeric cytokine, interleukin-23 (IL-23) is emerging as a key player in both the innate and the adaptive T helper (Th)17 driven immune response as well as an initiator of several autoimmune diseases. The rate-limiting element of IL-23 production is believed to be driven by expression of the unique p19 subunit encoded by IL23A. We set out to perform comprehensive DNA sequencing of this previously under-studied gene in 96 individuals from two evolutionary distinct human population groups, Southern African Bantu and European. We observed a total of 33 different DNA variants within these two groups, 22 (67%) of which are currently not reported in any available database. We further demonstrate both inter-population and intra-species sequence conservation within the coding and known regulatory regions of IL23A, supporting a critical physiological role for IL-23. We conclude that IL23A may have undergone positive selection pressure directed towards conservation, suggesting that functional genetic variants within IL23A will have a significant impact on the host immune response.
Cancer Genetics Group, Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
Elizabeth A
EA
Tindall
Vanessa M
VM
Hayes
D001483:Base Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA
C508840:IL23A protein, human; D053760:Interleukin-23 Subunit p19