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PloS one2013; 8(5); e64736; doi: 10.1371/journal.pone.0064736

Natural killer cell receptor genes in the family Equidae: not only Ly49.

Abstract: 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.
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Publication Date: 2013-05-28 PubMed ID: 23724088PubMed Central: PMC3665701DOI: 10.1371/journal.pone.0064736Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines the variable nature and evolution of natural killer cell receptor (NKR) genes, with a particular focus on the family Equidae, which includes horses, asses and zebras. The studies reveal the presence of at least five highly conserved polymorphic Ly49 genes throughout this family. Additionally, a previously undetected functional KIR receptor protein molecule is suggested. The progression of these NKR genes across Perissodactyla could provide an insightful model for the study of evolutionary biology.

Natural Killer Cell Receptor Genes

  • Natural Killer (NK) cells are crucial to the immune system. They can recognize and respond to changes in cells through two main types of receptors: Killer cell immunoglobulin-like receptors (KIR) and killer cell lectin-like Ly49 receptors.
  • The genes encoding these receptors differ significantly across mammals, depending on the species. Some species have “single-copy low polymorphic NKR genes,” while others have “highly polymorphic multigene families.” This variability and rapid evolution are at the core of the study.

Ly49 Genes in Equidae

  • This research confirms what was previously believed about the presence of multiple Ly49-like genes in the horse. Furthermore, it expands upon this previous knowledge by showing that this is common throughout the entire family Equidae, consisting of horses, asses, and zebras.
  • At least five highly conserved polymorphic Ly49 genes have been detected in these species, confirming a broader expansion of Ly49 genes within the Equidae family than previously understood.

Functional KIR Genes in Equidae

  • While functional KIR genes were not previously observed in horses, this study suggests a potential functional KIR receptor protein molecule throughout all Equidae. The genomic organization and mRNA expression of this KIR3DL sequence suggests it could be functional, despite containing a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain.
  • No evidence of positive selection in the KIR3DL gene was detected. This signifies that this gene does not confer an observable evolutionary advantage or disadvantage to the species.

Implication and Significance

  • The results of this study indicate differences in NKR gene evolution within the order Perissodactyla, which includes both the Rhinocerotidae and Tapiridae families in addition to Equidae.
  • The research highlights how the order Perissodactyla and specifically its family Equidae, with expanded Ly49 genes and a potentially functional KIR gene, potentially represent a useful model for studying the evolutionary biology of NKR genes.

Cite This Article

APA
Futas J, Horin P. (2013). Natural killer cell receptor genes in the family Equidae: not only Ly49. PLoS One, 8(5), e64736. https://doi.org/10.1371/journal.pone.0064736

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 5
Pages: e64736
PII: e64736

Researcher Affiliations

Futas, Jan
  • Departmen of Animal Genetics, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic.
Horin, Petr

    MeSH Terms

    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • Chromosomes, Mammalian / genetics
    • Computer Simulation
    • Gene Frequency / genetics
    • Gene Fusion
    • Genome / genetics
    • Horses / genetics
    • Molecular Sequence Data
    • NK Cell Lectin-Like Receptor Subfamily A / genetics
    • Phylogeny
    • Polymorphism, Single Nucleotide / genetics
    • Receptors, Natural Killer Cell / chemistry
    • Receptors, Natural Killer Cell / genetics
    • Receptors, Natural Killer Cell / metabolism
    • Sequence Homology, Amino Acid

    Conflict of Interest Statement

    The authors have declared that no competing interests exist.

    References

    This article includes 41 references
    1. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S. Innate or adaptive immunity? The example of natural killer cells.. Science 2011 Jan 7;331(6013):44-9.
      pmc: PMC3089969pubmed: 21212348doi: 10.1126/science.1198687google scholar: lookup
    2. Parham P, Norman PJ, Abi-Rached L, Guethlein LA. Variable NK cell receptors exemplified by human KIR3DL1/S1.. J Immunol 2011 Jul 1;187(1):11-9.
      pmc: PMC3223120pubmed: 21690332doi: 10.4049/jimmunol.0902332google scholar: lookup
    3. Hao L, Klein J, Nei M. Heterogeneous but conserved natural killer receptor gene complexes in four major orders of mammals.. Proc Natl Acad Sci U S A 2006 Feb 28;103(9):3192-7.
      pmc: PMC1413923pubmed: 16492762doi: 10.1073/pnas.0511280103google scholar: lookup
    4. Kelley J, Walter L, Trowsdale J. Comparative genomics of natural killer cell receptor gene clusters.. PLoS Genet 2005 Aug;1(2):129-39.
      pmc: PMC1193534pubmed: 16132082doi: 10.1371/journal.pgen.0010027google scholar: lookup
    5. Guethlein LA, Abi-Rached L, Hammond JA, Parham P. The expanded cattle KIR genes are orthologous to the conserved single-copy KIR3DX1 gene of primates.. Immunogenetics 2007 Jun;59(6):517-22.
      pubmed: 17450355doi: 10.1007/s00251-007-0214-xgoogle scholar: lookup
    6. Hao L, Nei M. Genomic organization and evolutionary analysis of Ly49 genes encoding the rodent natural killer cell receptors: rapid evolution by repeated gene duplication.. Immunogenetics 2004 Aug;56(5):343-54.
      pubmed: 15316687doi: 10.1007/s00251-004-0703-0google scholar: lookup
    7. Mager DL, McQueen KL, Wee V, Freeman JD. Evolution of natural killer cell receptors: coexistence of functional Ly49 and KIR genes in baboons.. Curr Biol 2001 Apr 17;11(8):626-30.
      pubmed: 11369209doi: 10.1016/s0960-9822(01)00148-8google scholar: lookup
    8. Guethlein LA, Flodin LR, Adams EJ, Parham P. 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 2002 Jul 1;169(1):220-9.
      pubmed: 12077248doi: 10.4049/jimmunol.169.1.220google scholar: lookup
    9. Westgaard IH, Berg SF, Orstavik S, Fossum S, Dissen E. Identification of a human member of the Ly-49 multigene family.. Eur J Immunol 1998 Jun;28(6):1839-46.
      pubmed: 9645365doi: 10.1002/(sici)1521-4141(199806)28:06<1839::aid-immu1839>3.0.co;2-egoogle scholar: lookup
    10. Dobromylskyj MJ, Connelley T, Hammond JA, Ellis SA. Cattle Ly49 is polymorphic.. Immunogenetics 2009 Dec;61(11-12):789-95.
      pubmed: 19911177doi: 10.1007/s00251-009-0406-7google scholar: lookup
    11. Dobromylskyj M, Ellis S. Complexity in cattle KIR genes: transcription and genome analysis.. Immunogenetics 2007 Jun;59(6):463-72.
      pubmed: 17450354doi: 10.1007/s00251-007-0215-9google scholar: lookup
    12. Sambrook JG, Sehra H, Coggill P, Humphray S, Palmer S, Sims S, Takamatsu HH, Wileman T, Archibald AL, Beck S. Identification of a single killer immunoglobulin-like receptor (KIR) gene in the porcine leukocyte receptor complex on chromosome 6q.. Immunogenetics 2006 Jun;58(5-6):481-6.
      pubmed: 16738944doi: 10.1007/s00251-006-0110-9google scholar: lookup
    13. Hammond JA, Guethlein LA, Abi-Rached L, Moesta AK, Parham P. Evolution and survival of marine carnivores did not require a diversity of killer cell Ig-like receptors or Ly49 NK cell receptors.. J Immunol 2009 Mar 15;182(6):3618-27.
      pmc: PMC2754575pubmed: 19265140doi: 10.4049/jimmunol.0803026google scholar: lookup
    14. Gagnier L, Wilhelm BT, Mager DL. Ly49 genes in non-rodent mammals.. Immunogenetics 2003 May;55(2):109-15.
      pubmed: 12712264doi: 10.1007/s00251-003-0558-9google scholar: lookup
    15. Andersson L. How selective sweeps in domestic animals provide new insight into biological mechanisms.. J Intern Med 2012 Jan;271(1):1-14.
      pubmed: 21895806doi: 10.1111/j.1365-2796.2011.02450.xgoogle scholar: lookup
    16. Price SA, Bininda-Emonds ORP. A comprehensive phylogeny of extant horses, rhinos and tapirs (Perissodactyla) through data combination.. Zool Reihe 85: 277–292.
    17. Janova E, Matiasovic J, Vahala J, Vodicka R, Van Dyk E, Horin P. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.. Immunogenetics 2009 Jul;61(7):513-27.
      pubmed: 19557406doi: 10.1007/s00251-009-0380-0google scholar: lookup
    18. Trifonov VA, Musilova P, Kulemsina AI. Chromosome evolution in Perissodactyla.. Cytogenet Genome Res 2012;137(2-4):208-17.
      pubmed: 22813844doi: 10.1159/000339900google scholar: lookup
    19. Nergadze SG, Lupotto M, Pellanda P, Santagostino M, Vitelli V, Giulotto E. Mitochondrial DNA insertions in the nuclear horse genome.. Anim Genet 2010 Dec;41 Suppl 2:176-85.
      pubmed: 21070293doi: 10.1111/j.1365-2052.2010.02130.xgoogle scholar: lookup
    20. Takahashi T, Yawata M, Raudsepp T, Lear TL, Chowdhary BP, Antczak DF, Kasahara M. Natural killer cell receptors in the horse: evidence for the existence of multiple transcribed LY49 genes.. Eur J Immunol 2004 Mar;34(3):773-784.
      pubmed: 14991607doi: 10.1002/eji.200324695google scholar: lookup
    21. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction.. BMC Bioinformatics 2012 Jun 18;13:134.
      pmc: PMC3412702pubmed: 22708584doi: 10.1186/1471-2105-13-134google scholar: lookup
    22. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
      pmc: PMC3785132pubmed: 19892987doi: 10.1126/science.1178158google scholar: lookup
    23. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT.. Nucl Acids Symp Ser 41: 95–98.
    24. Zizzadoro C, Belloli C, Badino P, Ormas P. A rapid and simple method for the separation of pure lymphocytes from horse blood.. Vet Immunol Immunopathol 2002 Oct 8;89(1-2):99-104.
      pubmed: 12208055doi: 10.1016/s0165-2427(02)00185-xgoogle scholar: lookup
    25. Librado P, Rozas J. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data.. Bioinformatics 2009 Jun 1;25(11):1451-2.
      pubmed: 19346325doi: 10.1093/bioinformatics/btp187google scholar: lookup
    26. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.. Mol Biol Evol 2011 Oct;28(10):2731-9.
      pmc: PMC3203626pubmed: 21546353doi: 10.1093/molbev/msr121google scholar: lookup
    27. Mayor C, Brudno M, Schwartz JR, Poliakov A, Rubin EM, Frazer KA, Pachter LS, Dubchak I. VISTA : visualizing global DNA sequence alignments of arbitrary length.. Bioinformatics 2000 Nov;16(11):1046-7.
      pubmed: 11159318doi: 10.1093/bioinformatics/16.11.1046google scholar: lookup
    28. Vivian JP, Duncan RC, Berry R, O'Connor GM, Reid HH, Beddoe T, Gras S, Saunders PM, Olshina MA, Widjaja JM, Harpur CM, Lin J, Maloveste SM, Price DA, Lafont BA, McVicar DW, Clements CS, Brooks AG, Rossjohn J. Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B.. Nature 2011 Oct 23;479(7373):401-5.
      pmc: PMC3723390pubmed: 22020283doi: 10.1038/nature10517google scholar: lookup
    29. Brinkmeyer-Langford CL, Murphy WJ, Childers CP, Skow LC. A conserved segmental duplication within ELA.. Anim Genet 2010 Dec;41 Suppl 2:186-95.
      pubmed: 21070294doi: 10.1111/j.1365-2052.2010.02137.xgoogle scholar: lookup
    30. Tallmadge RL, Lear TL, Antczak DF. Genomic characterization of MHC class I genes of the horse.. Immunogenetics 2005 Nov;57(10):763-74.
      pubmed: 16220348doi: 10.1007/s00251-005-0034-9google scholar: lookup
    31. Tallmadge RL, Campbell JA, Miller DC, Antczak DF. Analysis of MHC class I genes across horse MHC haplotypes.. Immunogenetics 2010 Mar;62(3):159-72.
      pmc: PMC2872545pubmed: 20099063doi: 10.1007/s00251-009-0420-9google scholar: lookup
    32. Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology.. Am J Reprod Immunol 2010 Oct;64(4):231-44.
      pubmed: 20618178doi: 10.1111/j.1600-0897.2010.00895.xgoogle scholar: lookup
    33. Vagnoni KE, Schram BR, Ginther OJ, Lunn DP. Susceptibility of equine chorionic girdle cells to lymphokine-activated killer cell activity.. Am J Reprod Immunol 1996 Sep;36(3):184-90.
      pubmed: 8874715doi: 10.1111/j.1600-0897.1996.tb00160.xgoogle scholar: lookup
    34. Noronha LE, Huggler KE, de Mestre AM, Miller DC, Antczak DF. Molecular evidence for natural killer-like cells in equine endometrial cups.. Placenta 2012 May;33(5):379-86.
      pmc: PMC3319276pubmed: 22357194doi: 10.1016/j.placenta.2012.01.018google scholar: lookup
    35. Brown D, Trowsdale J, Allen R. The LILR family: modulators of innate and adaptive immune pathways in health and disease.. Tissue Antigens 2004 Sep;64(3):215-25.
      pubmed: 15304001doi: 10.1111/j.0001-2815.2004.00290.xgoogle scholar: lookup
    36. Hogan L, Bhuju S, Jones DC, Laing K, Trowsdale J, Butcher P, Singh M, Vordermeier M, Allen RL. Characterisation of bovine leukocyte Ig-like receptors.. PLoS One 2012;7(4):e34291.
      pmc: PMC3317502pubmed: 22485161doi: 10.1371/journal.pone.0034291google scholar: lookup
    37. Oakenfull EA, Clegg JB. Phylogenetic relationships within the genus Equus and the evolution of alpha and theta globin genes.. J Mol Evol 1998 Dec;47(6):772-83.
      pubmed: 9847419doi: 10.1007/pl00006436google scholar: lookup
    38. McCue ME, Bannasch DL, Petersen JL, Gurr J, Bailey E, Binns MM, Distl O, Guérin G, Hasegawa T, Hill EW, Leeb T, Lindgren G, Penedo MC, Røed KH, Ryder OA, Swinburne JE, Tozaki T, Valberg SJ, Vaudin M, Lindblad-Toh K, Wade CM, Mickelson JR. A high density SNP array for the domestic horse and extant Perissodactyla: utility for association mapping, genetic diversity, and phylogeny studies.. PLoS Genet 2012 Jan;8(1):e1002451.
      pmc: PMC3257288pubmed: 22253606doi: 10.1371/journal.pgen.1002451google scholar: lookup
    39. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees.. Mol Biol Evol 1987 Jul;4(4):406-25.
      pubmed: 3447015doi: 10.1093/oxfordjournals.molbev.a040454google scholar: lookup
    40. Felsenstein J. CONFIDENCE LIMITS ON PHYLOGENIES: AN APPROACH USING THE BOOTSTRAP.. Evolution 1985 Jul;39(4):783-791.
      pubmed: 28561359doi: 10.1111/j.1558-5646.1985.tb00420.xgoogle scholar: lookup
    41. Nei M, Kumar S. Molecular Evolution and Phylogenetics.. .

    Citations

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    1. Dornburg A, Mallik R, Wang Z, Bernal MA, Thompson B, Bruford EA, Nebert DW, Vasiliou V, Yohe LR, Yoder JA, Townsend JP. Placing human gene families into their evolutionary context. Hum Genomics 2022 Nov 11;16(1):56.
      doi: 10.1186/s40246-022-00429-5pubmed: 36369063google scholar: lookup
    2. Plasil M, Futas J, Jelinek A, Burger PA, Horin P. Comparative Genomics of the Major Histocompatibility Complex (MHC) of Felids. Front Genet 2022;13:829891.
      doi: 10.3389/fgene.2022.829891pubmed: 35309138google scholar: lookup
    3. Klumplerova M, Splichalova P, Oppelt J, Futas J, Kohutova A, Musilova P, Kubickova S, Vodicka R, Orlando L, Horin P. Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae. BMC Genomics 2020 Sep 30;21(1):677.
      doi: 10.1186/s12864-020-07089-6pubmed: 32998693google scholar: lookup
    4. Todd ET, Thomson PC, Hamilton NA, Ang RA, Lindgren G, Viklund Å, Eriksson S, Mikko S, Strand E, Velie BD. A genome-wide scan for candidate lethal variants in Thoroughbred horses. Sci Rep 2020 Aug 4;10(1):13153.
      doi: 10.1038/s41598-020-68946-8pubmed: 32753654google scholar: lookup
    5. Stejskalova K, Janova E, Horecky C, Horecka E, Vaclavek P, Hubalek Z, Relling K, Cvanova M, D'Amico G, Mihalca AD, Modry D, Knoll A, Horin P. Associations between the presence of specific antibodies to the West Nile Virus infection and candidate genes in Romanian horses from the Danube delta. Mol Biol Rep 2019 Aug;46(4):4453-4461.
      doi: 10.1007/s11033-019-04900-wpubmed: 31175514google scholar: lookup
    6. Schwartz JC, Gibson MS, Heimeier D, Koren S, Phillippy AM, Bickhart DM, Smith TP, Medrano JF, Hammond JA. The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation. Immunogenetics 2017 Apr;69(4):255-269.
      doi: 10.1007/s00251-017-0973-ypubmed: 28180967google scholar: lookup
    7. Carrillo-Bustamante P, Keşmir C, de Boer RJ. The evolution of natural killer cell receptors. Immunogenetics 2016 Jan;68(1):3-18.
      doi: 10.1007/s00251-015-0869-7pubmed: 26392015google scholar: lookup
    8. Guethlein LA, Norman PJ, Hilton HG, Parham P. Co-evolution of MHC class I and variable NK cell receptors in placental mammals. Immunol Rev 2015 Sep;267(1):259-82.
      doi: 10.1111/imr.12326pubmed: 26284483google scholar: lookup
    9. Sanderson ND, Norman PJ, Guethlein LA, Ellis SA, Williams C, Breen M, Park SD, Magee DA, Babrzadeh F, Warry A, Watson M, Bradley DG, MacHugh DE, Parham P, Hammond JA. Definition of the cattle killer cell Ig-like receptor gene family: comparison with aurochs and human counterparts. J Immunol 2014 Dec 15;193(12):6016-30.
      doi: 10.4049/jimmunol.1401980pubmed: 25398326google scholar: lookup
    10. Stejskalova K, Vychodilova L, Janova E, Oppelt J, Horin P. Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds. Vet Med Sci 2025 Mar;11(2):e70230.
      doi: 10.1002/vms3.70230pubmed: 39918481google scholar: lookup
    11. Futas J, Jelinek AL, Burger PA, Horin P. Comparative genomics of the Natural Killer Complex in carnivores. Front Immunol 2024;15:1459122.
      doi: 10.3389/fimmu.2024.1459122pubmed: 39421739google scholar: lookup
    12. Stejskalova K, Janova E, Splichalova P, Futas J, Oppelt J, Vodicka R, Horin P. Twelve toll-like receptor (TLR) genes in the family Equidae - comparative genomics, selection and evolution. Vet Res Commun 2024 Apr;48(2):725-741.
      doi: 10.1007/s11259-023-10245-4pubmed: 37874499google scholar: lookup
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