SHORT COMMUNICATION IL26 gene inactivation in Equidae M. Shakhsi-Niaei* † , M. Dr€ ogem€ uller*, V. Jagannathan*, V. Gerber ‡ and T. Leeb* *Vetsuisse Faculty, Institute of Genetics, University of Bern, Bremgartenstrasse 109a, 3001, Bern, Switzerland. † Genetics Group, Science Faculty, University of Shahrekord, Rahbar Boulevard, Shahrekord, Iran. ‡ Vetsuisse Faculty, Swiss Institute of Equine Medicine, University of Bern and ALP-Haras, L€ anggassstrasse 124, 3001, Bern, Switzerland. Summary Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution. Keywords donkey, evolution, horse, IL26, immune system, interleukin, Przewalski horse. Interleukin 26 (IL26) – previously called AK155 – was discovered after transformation of T lymphocytes with herpesvirus saimiri (Knappe et al. 2000), but the gene is more broadly expressed subsequent to antigen-specific stimulation of Th17 cells. Single nucleotide polymorphisms (SNPs) within the IL26 gene are associated with an increased risk of certain autoimmune diseases, and such SNPs may provide useful as genetic markers for multiple sclerosis and rheumatoid arthritis. Furthermore, expression levels of IL26 may reflect inflammation in autoimmune diseases (Donnelly et al. 2010). IL26 has a sequence homology of about 25% with IL10 and belongs to the IL10 cytokine family, which also comprises IL10, IL19, IL20, IL22, IL24, IL28, IL29, as well as the interferons and interferon-like molecules (Kotenko 2002; Renauld 2003; Commins et al. 2008). Interestingly, and despite its sequence homology with IL10, IL26 binds to a different cell surface receptor composed of the IL20R1 and IL10R2 chains (Donnelly et al. 2010). IL26 shows an overlapping but not identical expression profile with IFNG and also IL22 (Wilson et al. 2007; Manel et al. 2008; P ene et al. 2008; Wan et al. 2011; Collins et al. 2012). The IL10 family genes are located in two clusters on two separate chromosomes in the human genome. The genes encoding for IL10, IL19, IL20 and IL24 lie on chromosome 1q32, whereas the genes for IL22, IL26 and IFNG all reside on human chromosome 12q15 (Fickenscher & Pirzer 2004). The human IL26 gene is composed of five exons that are separated by four introns. Despite the low amino acid sequence similarity of the human IL26 protein to that of non-mammalian species, such as zebrafish or frogs (17–30%), the IL26 gene is conserved in most vertebrate species with a known exception in the mouse (Fickenscher & Pirzer 2004; Donnelly et al. 2010). Initially, we searched for the IL26 gene within the available genomic assemblies of different vertebrates. For species with an annotated IL26 gene, we used its mRNA and protein annotations for comparison. For other species without any available annotation or annotations not containing the evolutionary conserved five exons, we used the human IL26 mRNA sequence (NM_018402) and the SPIDEY mRNA to genomics alignment tool (Wheelan et al. 2001) to predict the exon annotations. Address for correspondence T. Leeb, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland. E-mail: tosso.leeb@vetsuisse.unibe.ch EMBL Accession numbers: HF564635, HF564636, HF564637, HF564638, HF564639. Accepted for publication 08 May 2013 doi: 10.1111/age.12069 770 © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics, 44, 770–772