Evidence of Balanced Diversity at the Chicken Interleukin 4 Receptor Alpha Chain Locus

Background: The comparative analysis of genome sequences emerging for several avian species with thefully sequenced chicken genome enables the genome-wide investigation of selective processes infunctionally important chicken genes. In particular, because of pathogenic challenges it is expected thatgenes involved in the chicken immune system are subject to particularly strong adaptive pressure.Signatures of selection detected by inter-species comparison may then be investigated at the populationlevel in global chicken populations to highlight potentially relevant functional polymorphisms.Results: Comparative evolutionary analysis of chicken (Gallus gallus) and zebra finch (Taeniopygia guttata)genes identified interleukin 4 receptor alpha-chain (IL-4Rα), a key cytokine receptor as a candidate with asignificant excess of substitutions at nonsynonymous sites, suggestive of adaptive evolution. Resequencingand detailed population genetic analysis of this gene in diverse village chickens from Asia and Africa,commercial broilers, and in outgroup species red jungle fowl (JF), grey JF, Ceylon JF, green JF, grey francolinand bamboo partridge, suggested elevated and balanced diversity across all populations at this gene, actingto preserve different high-frequency alleles at two nonsynonymous sites.Conclusion: Haplotype networks indicate that red JF is the primary contributor of diversity at chickenIL-4Rα: the signature of variation observed here may be due to the effects of domestication, admixtureand introgression, which produce high diversity. However, this gene is a key cytokine-binding receptor inthe immune system, so balancing selection related to the host response to pathogens cannot be excluded.