title: Two Orangutan Species Have Evolved DifferentKIRAlleles and Haplotypes.
abstract: The immune and reproductive functions of human NK cells are regulated by interactions of the C1 and C2 epitopes of HLA-C with C1-specific and C2-specific lineage III killer cell Ig-like receptors (KIR). This rapidly evolving and diverse system of ligands and receptors is restricted to humans and great apes. In this context, the orangutan has particular relevance because it represents an evolutionary intermediate, one having the C1 epitope and corresponding KIR but lacking the C2 epitope. Through a combination of direct sequencing,KIRgenotyping, and data mining from the Great Ape Genome Project, we characterized theKIRalleles and haplotypes for panels of 10 Bornean orangutans and 19 Sumatran orangutans. The orangutanKIRhaplotypes have between 5 and 10KIRgenes. The seven orangutan lineage IIIKIRgenes all locate to the centromeric region of theKIRlocus, whereas their human counterparts also populate the telomeric region. One lineage IIIKIRgene is Bornean specific, one is Sumatran specific, and five are shared. Of 12KIRgene-content haplotypes, 5 are Bornean specific, 5 are Sumatran specific, and 2 are shared. The haplotypes have different combinations of genes encoding activating and inhibitory C1 receptors that can be of higher or lower affinity. All haplotypes encode an inhibitory C1 receptor, but only some haplotypes encode an activating C1 receptor. Of 130KIRalleles, 55 are Bornean specific, 65 are Sumatran specific, and 10 are shared.
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305.|Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.
authors.forename: Lisbeth A
authors.identifier: 0000-0002-1301-8301
authors.initials: LA
authors.lastname: Guethlein
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305.|Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.
authors.forename: Paul J
authors.identifier: 0000-0001-8370-7703
authors.initials: PJ
authors.lastname: Norman
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.
authors.forename: Corinne M C
authors.initials: CM
authors.lastname: Heijmans
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.
authors.forename: Natasja G
authors.initials: NG
authors.lastname: de Groot
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305.|Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.
authors.forename: Hugo G
authors.identifier: 0000-0003-1488-7194
authors.initials: HG
authors.lastname: Hilton
authors.affiliation: Stanford Genome Technology Center, Palo Alto, CA 94304; and.
authors.forename: Farbod
authors.initials: F
authors.lastname: Babrzadeh
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305.|Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abi-Rached
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.|Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Bontrop
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305; peropa@stanford.edu.|Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
mesh_terms: D000483:Alleles; D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D019143:Evolution, Molecular; D006239:Haplotypes; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D057079:Pongo / Q000235:genetics* / Q000276:immunology*; D054340:Receptors, KIR / Q000235:genetics*; D013045:Species Specificity
chemical_list: D054340:Receptors, KIR