Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes.

Departmen of Animal Genetics University of Veterinary and Pharmaceutical Sciences Brno Brno Czech Republic

Zobrazit více v PubMed

Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, et al. (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331: 44–49. PubMed PMC

Parham P, Norman PJ, Abi-Rached L, Guethlein LA (2011) Variable NK cell receptors exemplified by human KIR3DL1/S1. J Immunol 187: 11–19. PubMed PMC

Hao L, Klein J, Nei M (2006) Heterogeneous but conserved natural killer receptor gene complexes in four major orders of mammals. Proc Natl Acad Sci U S A 103: 3192–3197. PubMed PMC

Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of natural killer cell receptor gene clusters. PLoS Genet 1: e27. PubMed PMC

Guethlein LA, Abi-Rached L, Hammond JA, Parham P (2007) The expanded cattle KIR genes are orthologous to the conserved single-copy KIR3DX1 gene of primates. Immunogenetics 59: 517–522. PubMed

Hao L, Nei M (2004) Genomic organization and evolutionary analysis of Ly49 genes encoding the rodent natural killer cell receptors: Rapid evolution by repeated gene duplication. Immunogenetics 56: 343–354. PubMed

Mager DL, McQueen KL, Wee V, Freeman JD (2001) Evolution of natural killer cell receptors: Coexistence of functional Ly49 and KIR genes in baboons. Curr Biol 11: 626–630. PubMed

Guethlein LA, Flodin LR, Adams EJ, Parham P (2002) NK cell receptors of the orangutan (Pongo pygmaeus): A pivotal species for tracking the coevolution of killer cell Ig-like receptors with MHC-C. J Immunol 169: 220–229. PubMed

Westgaard IH, Berg SF, Orstavik S, Fossum S, Dissen E (1998) Identification of a human member of the Ly-49 multigene family. Eur J Immunol 28: 1839–1846. PubMed

Dobromylskyj MJ, Connelley T, Hammond JA, Ellis SA (2009) Cattle Ly49 is polymorphic. Immunogenetics 61: 789–795. PubMed

Dobromylskyj M, Ellis S (2007) Complexity in cattle KIR genes: transcription and genome analysis. Immunogenetics 59: 463–472. PubMed

Sambrook JG, Sehra H, Coggill P, Humphray S, Palmer S, et al. (2006) Identification of a single killer immunoglobulin-like receptor (KIR) gene in the porcine leukocyte receptor complex on chromosome 6q. Immunogenetics 58: 481–486. PubMed

Hammond JA, Guethlein LA, Abi-Rached L, Moesta AK, Parham P (2009) Evolution and survival of marine carnivores did not require a diversity of killer cell Ig-like receptors or Ly49 NK cell receptors. J Immunol 182: 3618–3627. PubMed PMC

Gagnier L, Wilhelm BT, Mager DL (2003) Ly49 genes in non-rodent mammals. Immunogenetics 55: 109–115. PubMed

Andersson L (2012) How selective sweeps in domestic animals provide new insight into biological mechanisms. J Intern Med 271: 1–14. PubMed

Price SA, Bininda-Emonds ORP (2009) A comprehensive phylogeny of extant horses, rhinos and tapirs (Perissodactyla) through data combination. Zool Reihe 85: 277–292.

Janova E, Matiasovic J, Vahala J, Vodicka R, Van Dyk E, et al. (2009) Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae. Immunogenetics 61: 513–527. PubMed

Trifonov VA, Musilova P, Kulemsina AI (2012) Chromosome evolution in Perissodactyla. Cytogenet Genome Res 137: 208–217. PubMed

Nergadze SG, Lupotto M, Pellanda P, Santagostino M, Vitelli V, et al. (2010) Mitochondrial DNA insertions in the nuclear horse genome. Animal Genetics 41: 176–185. PubMed

Takahashi T, Yawata M, Raudsepp T, Lear TL, Bhanu P, et al. (2004) Natural killer cell receptors in the horse: evidence for the existence of multiple transcribed LY49 genes. Eur J Immunol 34: 773–784. PubMed

Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, et al. (2012) Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics 13: 134. PubMed PMC

Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, et al. (2009) Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 326: 865–867. PubMed PMC

Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41: 95–98.

Zizzadoro C, Belloli C, Badino P, Ormas P (2002) A rapid and simple method for the separation of pure lymphocytes from horse blood. Vet Immunol Immunopathol 89: 99–104. PubMed

Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25: 1451–1452. PubMed

Tamura K, Peterson D, Peterson N, Stecher G, Nei M, et al. (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28: 2731–2739. PubMed PMC

Mayor C, Brudno M, Schwartz JR, Poliakov A, Rubin EM, et al. (2000) VISTA: visualizing global DNA sequence alignments of arbitrary length. Bioinformatics 16: 1046–1047. PubMed

Vivian JP, Duncan RC, Berry R, O’Connor GM, Reid HH, et al. (2011) Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B. Nature. 479: 401–405. PubMed PMC

Brinkmeyer-Langford CL, Murphy WJ, Childers CP, Skow LC (2010) A conserved segmental duplication within ELA. Anim Genet 41 Suppl 2186–195. PubMed

Tallmadge RL, Lear TL, Antczak DF (2005) Genomic characterization of MHC class I genes of the horse. Immunogenetics 57: 763–774. PubMed

Tallmadge RL, Campbell JA, Miller DC, Antczak DF (2010) Analysis of MHC class I genes across horse MHC haplotypes. Immunogenetics 62: 159–172. PubMed PMC

Noronha LE, Antczak DF (2010) Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. Am J Reprod Immunol 64: 231–244. PubMed

Vagnoni KE, Schram BR, Ginther OJ, Lunn DP (1996) Susceptibility of equine chorionic girdle cells to lymphokine-activated killer cell activity. Am J Reprod Immunol 36: 184–190. PubMed

Noronha LE, Huggler KE, de Mestre AM, Miller DC, Antczak DF (2012) Molecular evidence for natural killer-like cells in equine endometrial cups. Placenta 33: 379–386. PubMed PMC

Brown D, Trowsdale J, Allen R (2004) The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens 64: 215–225. PubMed

Hogan L, Bhuju S, Jones DC, Laing K, Trowsdale J, et al. (2012) Characterisation of bovine leukocyte Ig-like receptors. PLoS One 7: e34291. PubMed PMC

Oakenfull EA, Clegg JB (1998) Phylogenetic relationships within the genus Equus and the evolution of alpha and theta globin genes. J Mol Evol 47: 772–783. PubMed

McCue ME, Bannasch DL, Petersen JL, Gurr J, Bailey E, et al. (2012) A high density SNP array for the domestic horse and extant Perissodactyla: utility for association mapping, genetic diversity, and phylogeny studies. PLoS Genet 8: e1002451. PubMed PMC

Saitou N, Nei M (1987) The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406–425. PubMed

Felsenstein J (1985) Confidence limits on phylogenies: An approach using the bootstrap. Evolution 39: 783–791. PubMed

Nei M, Kumar S (2000) Molecular Evolution and Phylogenetics. Oxford: Oxford University Press. 333 p.

Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds

Comparative genomics of the Natural Killer Complex in carnivores

Twelve toll-like receptor (TLR) genes in the family Equidae - comparative genomics, selection and evolution

Comparative Genomics of the Major Histocompatibility Complex (MHC) of Felids

Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae

Associations between the presence of specific antibodies to the West Nile Virus infection and candidate genes in Romanian horses from the Danube delta

Zobrazit více v PubMed

GENBANK
KC315949, KC315950, KC315951, KC315952, KC315953, KC315954, KC315955, KC315956, KC315957, KC315958, KC315959