Definition of the cattle killer cell Ig-like receptor gene family: comparison with aurochs and human counterparts.
Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig-like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle.
The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, United Kingdom;
Nicholas D
ND
Sanderson
Department of Structural Biology, Stanford University, Stanford, CA 94035; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94035;
Paul J
PJ
Norman
Department of Structural Biology, Stanford University, Stanford, CA 94035; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94035;
Lisbeth A
LA
Guethlein
The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, United Kingdom;
Shirley A
SA
Ellis
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27695;
Christina
C
Williams
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27695; Center for Comparative Medicine and Translational Research, Raleigh, NC 27539; Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599;
Matthew
M
Breen
Animal Genomics Laboratory, School of Agriculture and Food Science, College of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland;
Steven D E
SD
Park
Animal Genomics Laboratory, School of Agriculture and Food Science, College of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland;
David A
DA
Magee
Stanford Genome Technology Center, Palo Alto, CA 94304;
Farbod
F
Babrzadeh
Bioscience Information Technology Services, Biotechnology and Biological Sciences Research Council, Swindon SN2 1UH, United Kingdom;
Andrew
A
Warry
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, United Kingdom;
Mick
M
Watson
Smurfit Institute of Genetics, Trinity College, Dublin 2, Ireland; and.
Daniel G
DG
Bradley
Animal Genomics Laboratory, School of Agriculture and Food Science, College of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
David E
DE
MacHugh
Department of Structural Biology, Stanford University, Stanford, CA 94035; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94035;
Peter
P
Parham
The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, United Kingdom; john.hammond@pirbright.ac.uk.
John A
JA
Hammond
D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D015723:Gene Library; D056426:Genetic Loci; D016678:Genome; D006239:Haplotypes; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D010641:Phenotype; D010802:Phylogeny; D017452:Receptors, IgG / Q000378:metabolism; D054340:Receptors, KIR / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D016615:Telomere
D007136:Immunoglobulins; D017452:Receptors, IgG; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell