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PMID: 21206914 Published · epublish English Journal Article Research Support, N.I.H., Extramural

Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus.

PloS one ·Vol. 5 ·No. 12 ·2010-12-29 ·Pages e15115

Pyo CW, Guethlein LA, Vu Q, Wang R, Abi-Rached L, Norman PJ, Marsh SG, Miller JS, Parham P, Geraghty DE

Abstract

The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ~6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ~1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region.

MeSH Terms
Alleles Amino Acid Motifs Centromere/ultrastructure Gene Library Genetic Variation Haplotypes Humans Immunoglobulins/chemistry Phylogeny Receptors, KIR/genetics Recombination, Genetic Sequence Analysis, DNA Telomere/ultrastructure
Chemicals
Immunoglobulins Receptors, KIR
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pyo Chul-Woo
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Guethlein Lisbeth A
Vu Quyen
Wang Ruihan
Abi-Rached Laurent
Norman Paul J
Marsh Steven G E
Miller Jeffrey S
Parham Peter
Geraghty Daniel E
References (72)
72 references, click to expand
  1. Cutting edge: expansion of the KIR locus by unequal crossing over.
    J Immunol. 2003 Sep 1;171(5):2192-5 PMID: 12928362
  2. Closing gaps in the human genome with fosmid resources generated from multiple individuals.
    Nat Genet. 2008 Jan;40(1):96-101 PMID: 18157130
  3. Multiple copies of KIR 3DL/S1 and KIR 2DL4 genes identified in a number of individuals.
    Hum Immunol. 2003 Jul;64(7):729-32 PMID: 12826375
  4. Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression.
    Immunogenetics. 2002 Nov;54(8):543-50 PMID: 12439616
  5. HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes.
    Immunogenetics. 2006 May;58(4):241-51 PMID: 16570139
  6. MHC class I molecules and KIRs in human history, health and survival.
    Nat Rev Immunol. 2005 Mar;5(3):201-14 PMID: 15719024
  7. SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex.
    Immunogenetics. 2004 Jul;56(4):225-37 PMID: 15185041
  8. Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations.
    Genes Immun. 2002 Apr;3(2):86-95 PMID: 11960306
  9. The genomic context of natural killer receptor extended gene families.
    Immunol Rev. 2001 Jun;181:20-38 PMID: 11513141
  10. Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis.
    J Exp Med. 2001 May 21;193(10):1159-67 PMID: 11369787
  11. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS.
    Nat Genet. 2002 Aug;31(4):429-34 PMID: 12134147
  12. Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype.
    J Immunol. 2002 Mar 1;168(5):2307-15 PMID: 11859120
  13. KIR in type 1 diabetes: disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects.
    Diabetes. 2003 Oct;52(10):2639-42 PMID: 14514651
  14. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.
    Science. 2004 Aug 6;305(5685):872-4 PMID: 15297676
  15. Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family.
    Crit Rev Immunol. 2002;22(5-6):463-82 PMID: 12803322
  16. Genetics of the immune response: identifying immune variation within the MHC and throughout the genome.
    Immunol Rev. 2002 Dec;190:69-85 PMID: 12493007
  17. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data.
    Bioinformatics. 2009 Jun 1;25(11):1451-2 PMID: 19346325
  18. Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands.
    Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18692-7 PMID: 19837691
  19. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform.
    Nucleic Acids Res. 2002 Jul 15;30(14):3059-66 PMID: 12136088
  20. Plasticity in the organization and sequences of human KIR/ILT gene families.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4778-83 PMID: 10781084
  21. Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to psoriasis vulgaris.
    J Invest Dermatol. 2004 May;122(5):1133-6 PMID: 15140215
  22. Recognition of HLA-G by the NK cell receptor KIR2DL4 is not essential for human reproduction.
    Eur J Immunol. 2003 Mar;33(3):639-44 PMID: 12616484
  23. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping.
    Annu Rev Genomics Hum Genet. 2008;9:403-33 PMID: 18593304
  24. Natural selection drives recurrent formation of activating killer cell immunoglobulin-like receptor and Ly49 from inhibitory homologues.
    J Exp Med. 2005 Apr 18;201(8):1319-32 PMID: 15837816
  25. High KIR diversity in Amerindians is maintained using few gene-content haplotypes.
    Immunogenetics. 2006 Jun;58(5-6):474-80 PMID: 16738943
  26. Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes.
    Genomics. 2006 May;87(5):561-71 PMID: 16434165
  27. Paleontological evidence to date the tree of life.
    Mol Biol Evol. 2007 Jan;24(1):26-53 PMID: 17047029
  28. Targeted, haplotype-resolved resequencing of long segments of the human genome.
    Genomics. 2005 Dec;86(6):759-66 PMID: 16249066
  29. Nomenclature for factors of the HLA system, 2004.
    Tissue Antigens. 2005 Apr;65(4):301-69 PMID: 15787720
  30. Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific.
    Eur J Immunol. 2004 Jun;34(6):1673-9 PMID: 15162437
  31. Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B.
    J Immunol. 2007 Jan 1;178(1):33-7 PMID: 17182537
  32. Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris.
    Hum Immunol. 2004 Jul;65(7):758-66 PMID: 15310528
  33. Divergent and convergent evolution of NK-cell receptors.
    Trends Immunol. 2001 Jan;22(1):52-7 PMID: 11286693
  34. PAML 4: phylogenetic analysis by maximum likelihood.
    Mol Biol Evol. 2007 Aug;24(8):1586-91 PMID: 17483113
  35. Immunology of placentation in eutherian mammals.
    Nat Rev Immunol. 2006 Aug;6(8):584-94 PMID: 16868549
  36. Cutting edge: susceptibility to psoriatic arthritis: influence of activating killer Ig-like receptor genes in the absence of specific HLA-C alleles.
    J Immunol. 2002 Sep 15;169(6):2818-22 PMID: 12218090
  37. The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense.
    Annu Rev Genomics Hum Genet. 2006;7:277-300 PMID: 16824023
  38. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia.
    Blood. 2009 Jan 15;113(3):726-32 PMID: 18945962
  39. Probability of finding HLA-mismatched related or unrelated marrow or cord blood donors.
    Hum Immunol. 2000 Aug;61(8):834-40 PMID: 10980395
  40. Regulation of inhibitory and activating killer-cell Ig-like receptor expression occurs in T cells after termination of TCR rearrangements.
    J Immunol. 2001 Feb 15;166(4):2487-94 PMID: 11160309
  41. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants.
    Science. 2002 Mar 15;295(5562):2097-100 PMID: 11896281
  42. The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated.
    Eur J Immunol. 2005 Jan;35(1):16-24 PMID: 15580659
  43. Single haplotype analysis demonstrates rapid evolution of the killer immunoglobulin-like receptor (KIR) loci in primates.
    Genome Res. 2005 Jan;15(1):25-35 PMID: 15632087
  44. Some human KIR haplotypes contain two KIR2DL5 genes: KIR2DL5A and KIR2DL5B.
    Immunogenetics. 2002 Aug;54(5):314-9 PMID: 12185535
  45. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.
    J Exp Med. 2004 Oct 18;200(8):957-65 PMID: 15477349
  46. Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes.
    Genes Immun. 2008 Jul;9(5):431-7 PMID: 18480828
  47. Natural killer cells remember: an evolutionary bridge between innate and adaptive immunity?
    Eur J Immunol. 2009 Aug;39(8):2059-64 PMID: 19637199
  48. Multiple sequence alignment with Clustal X.
    Trends Biochem Sci. 1998 Oct;23(10):403-5 PMID: 9810230
  49. Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference.
    Clin Immunol. 2009 Nov;133(2):171-8 PMID: 19481979
  50. Hidden talents of natural killers: NK cells in innate and adaptive immunity.
    EMBO Rep. 2009 Oct;10(10):1103-10 PMID: 19730434
  51. Killer Ig-like receptor haplotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets.
    J Immunol. 2002 Nov 1;169(9):5118-29 PMID: 12391228
  52. Human diversity in killer cell inhibitory receptor genes.
    Immunity. 1997 Dec;7(6):753-63 PMID: 9430221
  53. Evolutionary vignettes of natural killer cell receptors.
    Curr Opin Immunol. 2007 Oct;19(5):553-60 PMID: 17884420
  54. Activating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemias.
    Clin Exp Immunol. 2009 Sep;157(3):325-31 PMID: 19664139
  55. Regulation of NK cell responsiveness to achieve self-tolerance and maximal responses to diseased target cells.
    Immunol Rev. 2008 Aug;224:85-97 PMID: 18759922
  56. Genetic divergence of the rhesus macaque major histocompatibility complex.
    Genome Res. 2004 Aug;14(8):1501-15 PMID: 15289473
  57. PAML: a program package for phylogenetic analysis by maximum likelihood.
    Comput Appl Biosci. 1997 Oct;13(5):555-6 PMID: 9367129
  58. Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002.
    Immunogenetics. 2003 Jul;55(4):220-6 PMID: 12838378
  59. Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes.
    Immunogenetics. 2002 Jul;54(4):221-9 PMID: 12136333
  60. RDP2: recombination detection and analysis from sequence alignments.
    Bioinformatics. 2005 Jan 15;21(2):260-2 PMID: 15377507
  61. KIR2DL5 alleles mark certain combination of activating KIR genes.
    Genes Immun. 2008 Jul;9(5):470-80 PMID: 18509341
  62. Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes.
    Genome Res. 2009 May;19(5):757-69 PMID: 19411600
  63. Evolution of killer cell Ig-like receptor (KIR) genes: definition of an orangutan KIR haplotype reveals expansion of lineage III KIR associated with the emergence of MHC-C.
    J Immunol. 2007 Jul 1;179(1):491-504 PMID: 17579070
  64. Association of killer cell immunoglobulin-like receptors with scleroderma.
    Arthritis Rheum. 2004 May;50(5):1561-5 PMID: 15146426
  65. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes.
    Blood. 2005 Jun 15;105(12):4878-84 PMID: 15731175
  66. The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism.
    Immunol Rev. 2002 Dec;190:40-52 PMID: 12493005
  67. Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis.
    J Immunol. 2004 Oct 1;173(7):4273-6 PMID: 15383555
  68. Comparative genomic analysis, diversity and evolution of two KIR haplotypes A and B.
    Gene. 2004 Jun 23;335:121-31 PMID: 15194195
  69. KIR haplotypes defined by segregation analysis in 59 Centre d'Etude Polymorphisme Humain (CEPH) families.
    Immunogenetics. 2008 Dec;60(12):767-74 PMID: 18972110
  70. Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families.
    Hum Immunol. 2005 Feb;66(2):146-54 PMID: 15695000
  71. MEGA: a biologist-centric software for evolutionary analysis of DNA and protein sequences.
    Brief Bioinform. 2008 Jul;9(4):299-306 PMID: 18417537
  72. KIR haplotype content at the allele level in 77 Northern Irish families.
    Immunogenetics. 2007 Feb;59(2):145-58 PMID: 17200871
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0015115
Published
2010-12-29
Epub
2010-00-29
Pages
e15115
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3012066
Subset
IM
Grants
NCRR NIH HHS · R42 RR018669 · United States
NCI NIH HHS · CA111412 · United States
NCRR NIH HHS · R41 RR018669 · United States
NCRR NIH HHS · RR018669 · United States
NCI NIH HHS · P01 CA111412 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0015115 PMC Full Text View journal details
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