KIR typing in chimpanzees. Chimpanzee KIR

Chimpanzees are humans’ closest living relative, and both species share a common ancestor that lived approximately 5-6 million years ago. Based on their genetics and geographical distribution four subspecies of chimpanzees are recognized, namely Pan troglodytes verus, P.t. troglodytes, P.t. schweinfurthii, and P.t. ellioti. Killer cell immunoglobulin-like receptors (KIR) are expressed on NK cells and subsets of T-cells, and may interact with MHC class I molecules. All simian primate species express KIRs, and in each species unique KIR genes may be present. Humans and chimpanzees, however, share the orthologous gene KIR2DL5 and the framework genes 3DL3, DP, 2DL4 and the telomeric 3DL. A comparison of KIR transcriptome data in humans and rhesus macaques, revealed that next to allelic polymorphism, copy number variation, and stochastic expression profiles, alternative splicing adds an additional layer of complexity to the primate KIR system. So far, not much is known about chimpanzee KIR isoforms. We investigated the KIR transcriptome of Western chimpanzees (P.t.verus) by using Single Molecule, Real-Time (SMRT) sequencing on a Pacific Bioscience’s (PacBio) Sequel platform. The panel comprised founder animals and their offspring, which allowed the reconstruction of KIR haplotypes and the confirmation of new genes/alleles by segregation analyses. Within the panel, we confirmed 16 Patr-KIR alleles and discovered 12 new alleles. Moreover, abundant alternative splicing events are observed for chimpanzees KIR transcripts, and like in humans and rhesus macaques, this included exon skipping, insertions, and deletions. Posttranscriptional modification of KIR transcripts seems to be conserved in primates, and the structural and putative functional diversity generated by alternative splicing events might have important functional implications in health and disease.