Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus

BMC Genomics

W Ivan Morrison¹  Cassandra W Longhi²  Kathryn Degnan¹  Timothy K Connelley¹ 

[1] The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, Scotland, UK;The Moredun Group, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, Scotland EH26 0PZ, UK

关键词: Evolution;    Duplication;    TR;    TRA/TRD locus;    Bovine;   

Others  :  1092217
DOI  :  10.1186/1471-2164-15-994

 received in 2014-04-14, accepted in 2014-11-04,  发布年份 2014

【 摘 要 】

Background

The TRA/TRD locus contains the genes for V(D)J somatic rearrangement of TRA and TRD chains expressed by αβ and γδ T cells respectively. Previous studies have demonstrated that the bovine TRA/TRD locus contains an exceptionally large number of TRAV/TRDV genes. In this study we combine genomic and transcript analysis to provide insights into the evolutionary development of the bovine TRA/TRD locus and the remarkable TRAV/TRDV gene repertoire.

Results

Annotation of the UMD3.1 assembly identified 371 TRAV/TRDV genes (distributed in 42 subgroups), 3 TRDJ, 6 TRDD, 62 TRAJ and single TRAC and TRDC genes, most of which were located within a 3.5 Mb region of chromosome 10. Most of the TRAV/TRDV subgroups have multiple members and several have undergone dramatic expansion, most notably TRDV1 (60 genes). Wide variation in the proportion of pseudogenes within individual subgroups, suggest that differential ‘birth’ and ‘death’ rates have been used to form a functional bovine TRAV/TRDV repertoire which is phylogenetically distinct from that of humans and mice. The expansion of the bovine TRAV/TRDV gene repertoire has predominantly been achieved through a complex series of homology unit (regions of DNA containing multiple gene) replications. Frequent co-localisation within homology units of genes from subgroups with low and high pseudogene proportions suggest that replication of homology units driven by evolutionary selection for the former may have led to a ‘collateral’ expansion of the latter. Transcript analysis was used to define the TRAV/TRDV subgroups available for recombination of TRA and TRD chains and demonstrated preferential usage of different subgroups by the expressed TRA and TRD repertoires, indicating that TRA and TRD selection have had distinct impacts on the evolution of the TRAV/TRDV repertoire.

Conclusion

Both TRA and TRD selection have contributed to the evolution of the bovine TRAV/TRDV repertoire. However, our data suggest that due to homology unit duplication TRD selection for TRDV1 subgroup expansion may have substantially contributed to the genomic expansion of several TRAV subgroups. Such data demonstrate how integration of genomic and transcript data can provide a more nuanced appreciation of the evolutionary dynamics that have led to the dramatically expanded bovine TRAV/TRDV repertoire.

【 授权许可】

   
2014 Connelley et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]McBlane JF, van Gent DC, Ramsden DA, Romeo C, Cuomo CA, Gellert M, Oettinger MA: Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell 1995, 83(3):387-395.
• [2]Davis MM, Bjorkman PJ: T-cell antigen receptor genes and T-cell recognition. Nature 1988, 334(6181):395-402.
• [3]Nikolich-Zugich J, Slifka MK, Messaoudi I: The many important facets of T-cell repertoire diversity. Nat Rev Immunol 2004, 4(2):123-132.
• [4]Rowen L, Koop BF, Hood L: The complete 685-kilobase DNA sequence of the human beta T cell receptor locus. Science 1996, 272(5269):1755-1762.
• [5]Osipovich O, Oltz EM: Regulation of antigen receptor gene assembly by genetic-epigenetic crosstalk. Semin Immunol 2010, 22(6):313-322.
• [6]Schlissel MS: Regulating antigen-receptor gene assembly. Nat Rev Immunol 2003, 3(11):890-899.
• [7]Glusman G, Rowen L, Lee I, Boysen C, Roach JC, Smit AF, Wang K, Koop BF, Hood L: Comparative genomics of the human and mouse T cell receptor loci. Immunity 2001, 15(3):337-349.
• [8]Connelley T, Aerts J, Law A, Morrison WI: Genomic analysis reveals extensive gene duplication within the bovine TRB locus. BMC Genomics 2009, 10:192. BioMed Central Full Text
• [9]Mineccia M, Massari S, Linguiti G, Ceci L, Ciccarese S, Antonacci R: New insight into the genomic structure of dog T cell receptor beta (TRB) locus inferred from expression analysis. Dev Comp Immunol 2012, 37(2):279-293.
• [10]Nei M, Gu X, Sitnikova T: Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci U S A 1997, 94(15):7799-7806.
• [11]Nei M, Rooney AP: Concerted and birth-and-death evolution of multigene families. Annu Rev Genet 2005, 39:121-152.
• [12]Su C, Nei M: Evolutionary dynamics of the T-cell receptor VB gene family as inferred from the human and mouse genomic sequences. Mol Biol Evol 2001, 18(4):503-513.
• [13]Lefranc M-P, Giudicelli V, Ginestoux C, Jabado-Michaloud J, Folch G, Bellahcene F, Wu Y, Gemrot E, Brochet X, Lane J, Regnier L, Ehrenmann F, Lefranc G, Duroux P: IMGT®, the international ImMunoGeneTics information system®. Nucl Acids Res 2009, 37:D1006-D1012.
• [14]Herzig CT, Lefranc MP, Baldwin CL: Annotation and classification of the bovine T cell receptor delta genes. BMC Genomics 2010, 11:100. BioMed Central Full Text
• [15]Reinink P, Van Rhijn I: The bovine T cell receptor alpha/delta locus contains over 400 V genes and encodes V genes without CDR2. Immunogenetics 2009, 61(7):541-549.
• [16]Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marçais G, Roberts M, Subramanian P, Yorke JA: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol 2009, 10(4):R42. BioMed Central Full Text
• [17]Herzig CT, Blumerman SL, Baldwin CL: Identification of three new bovine T-cell receptor delta variable gene subgroups expressed by peripheral blood T cells. Immunogenetics 2006, 58(9):746-757.
• [18]Blumerman SL, Herzig CT, Rogers AN, Telfer JC, Baldwin CL: Differential TCR gene usage between WC1- and WC1+ ruminant gammadelta T cell subpopulations including those responding to bacterial antigen. Immunogenetics 2006, 58(8):680-692.
• [19]Hein WR, Dudler L: TCR gamma delta + cells are prominent in normal bovine skin and express a diverse repertoire of antigen receptors. Immunology 1997, 91(1):58-64.
• [20]Ishiguro N, Aida Y, Shinagawa T, Shinagawa M: Molecular structures of cattle T-cell receptor gamma and delta chains predominantly expressed on peripheral blood lymphocytes. Immunogenetics 1993, 38(6):437-443.
• [21]Van Rhijn I, Spiering R, Smits M, van Blokland MT, de Weger R, van Eden W, Rutten VP, Koets AP: Highly diverse TCR delta chain repertoire in bovine tissues due to the use of up to four D segments per delta chain. Mol Immunol 2007, 44(12):3155-3161.
• [22]Ishiguro N, Tanaka A, Shinagawa M: Sequence analysis of bovine T-cell receptor alpha chain. Immunogenetics 1990, 31(1):57-60.
• [23]Lahmers KK, Norimine J, Abrahamsen MS, Palmer GH, Brown WC: The CD4+ T cell immunodominant Anaplasma marginale major surface protein 2 stimulates gammadelta T cell clones that express unique T cell receptors. J Leukoc Biol 2005, 77(2):199-208.
• [24]Quigley MF, Almeida JR, Price DA, Douek DC: Unbiased molecular analysis of T cell receptor expression using template-switch anchored RT-PCR. Curr Protoc Immunol 2011, Chapter 10:Unit10-Unit33.
• [25]Arden B, Clark SP, Kabelitz D, Mak TW: Mouse T-cell receptor variable gene segment families. Immunogenetics 1995, 42(6):501-530.
• [26]Arden B, Clark SP, Kabelitz D, Mak TW: Human T-cell receptor variable gene segment families. Immunogenetics 1995, 42(6):455-500.
• [27]Litman GW, Rast JP, Fugmann SD: The origins of vertebrate adaptive immunity. Nat Rev Immunol 2010, 10(8):543-553.
• [28]Richards MH, Nelson JL: The evolution of vertebrate antigen receptors: a phylogenetic approach. Mol Biol Evol 2000, 17(1):146-155.
• [29]Hedges SB, Dudley J, Kumar S: TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 2006, 22(23):2971-2972.
• [30]Bosc N, Lefranc MP: The mouse (Mus musculus) T cell receptor alpha (TRA) and delta (TRD) variable genes. Dev Comp Immunol 2003, 27(6–7):465-497.
• [31]Sitnikova T, Su C: Coevolution of immunoglobulin heavy- and light-chain variable-region gene families. Mol Biol Evol 1998, 15(6):617-625.
• [32]Lefranc MP: IMGT, the international ImMunoGeneTics database. Nucleic Acids Res 2001, 29(1):207-209.
• [33]Niku M, Liljavirta J, Durkin K, Schroderus E, Iivanainen A: The bovine genomic DNA sequence data reveal three IGHV subgroups, only one of which is functionally expressed. Dev Comp Immunol 2012, 37(3–4):457-461.
• [34]Ekman A, Niku M, Liljavirta J, Iivanainen A: Bos taurus genome sequence reveals the assortment of immunoglobulin and surrogate light chain genes in domestic cattle. BMC Immunol 2009, 10:22. BioMed Central Full Text
• [35]Antonacci R, Lanave C, Del Faro L, Vaccarelli G, Ciccarese S, Massari S: Artiodactyl emergence is accompanied by the birth of an extensive pool of diverse germline TRDV1 genes. Immunogenetics 2005, 57(3–4):254-266.
• [36]Pang DJ, Neves JF, Sumaria N, Pennington DJ: Understanding the complexity of gammadelta T-cell subsets in mouse and human. Immunology 2012, 136(3):283-290.
• [37]Kress E, Hedges JF, Jutila MA: Distinct gene expression in human Vdelta1 and Vdelta2 gammadelta T cells following non-TCR agonist stimulation. Mol Immunol 2006, 43(12):2002-2011.
• [38]Hoek A, Rutten VP, Kool J, Arkesteijn GJ, Bouwstra RJ, Van Rhijn I, Koets AP: Subpopulations of bovine WC1(+) gammadelta T cells rather than CD4(+)CD25(high) Foxp3(+) T cells act as immune regulatory cells ex vivo. Vet Res 2009, 40(1):6.
• [39]Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22(22):4673-4680.
• [40]Lefranc MP, Pommie C, Ruiz M, Giudicelli V, Foulquier E, Truong L, Thouvenin-Contet V, Lefranc G: IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol 2003, 27(1):55-77.
• [41]Akamatsu Y, Tsurushita N, Nagawa F, Matsuoka M, Okazaki K, Imai M, Sakano H: Essential residues in V(D)J recombination signals. J Immunol 1994, 153(10):4520-4529.
• [42]Hesse JE, Lieber MR, Mizuuchi K, Gellert M: V(D)J recombination: a functional definition of the joining signals. Genes Dev 1989, 3(7):1053-1061.
• [43]Schwartz S, Zhang Z, Frazer KA, Smit A, Riemer C, Bouck J, Gibbs R, Hardison R, Miller W: PipMaker–a web server for aligning two genomic DNA sequences. Genome Res 2000, 10(4):577-586.
• [44]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, 28(10):2731-2739.
• [45]Nei M, Kumar S: Molecular evolution and phylogenetics. Oxford, UK: Oxford University Press; 2000.
• [46]Lefranc MP: Nomenclature of the human T cell receptor genes. Curr Protoc Immunol 2001, Appendix 1:Appendix 1O.
• [47]Lai E, Concannon P, Hood L: Conserved organization of the human and murine T-cell receptor beta-gene families. Nature 1988, 331(6156):543-546.
• [48]Giese K, Kingsley C, Kirshner JR, Grosschedl R: Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. Genes Dev 1995, 9(8):995-1008.
• [49]Hernandez-Munain C, Roberts JL, Krangel MS: Cooperation among multiple transcription factors is required for access to minimal T-cell receptor alpha-enhancer chromatin in vivo. Mol Cell Biol 1998, 18(6):3223-3233.
• [50]Roberts JL, Lauzurica P, Krangel MS: Developmental regulation of VDJ recombination by the core fragment of the T cell receptor alpha enhancer. J Exp Med 1997, 185(1):131-140.
• [51]Balmelle N, Zamarreno N, Krangel MS, Hernandez-Munain C: Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer. J Immunol 2004, 173(8):5054-5063.
• [52]Hernandez-Munain C, Sleckman BP, Krangel MS: A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation. Immunity 1999, 10(6):723-733.
• [53]Spicuglia S, Payet D, Tripathi RK, Rameil P, Verthuy C, Imbert J, Ferrier P, Hempel WM: TCRalpha enhancer activation occurs via a conformational change of a pre-assembled nucleo-protein complex. EMBO J 2000, 19(9):2034-2045.
• [54]Redondo JM, Pfohl JL, Krangel MS: Identification of an essential site for transcriptional activation within the human T-cell receptor delta enhancer. Mol Cell Biol 1991, 11(11):5671-5680.
• [55]Hernandez-Munain C, Krangel MS: Distinct roles for c-Myb and core binding factor/polyoma enhancer-binding protein 2 in the assembly and function of a multiprotein complex on the TCR delta enhancer in vivo. J Immunol 2002, 169(8):4362-4369.