Genomic and comparative analysis of the T cell receptor gamma locus in two Equus species.
Abstract: The genus is the only extant genus of the Equidae family, which belongs to Perissodactyla, an order of mammals characterized by an odd number of toes (odd-toes ungulates). Taking advantage of the latest release of the genome assembly, we studied, for the first time in two organisms belonging to the genus, the horse () and the donkey (), the T cell receptor gamma (TRG) locus encoding the gamma chain of the γδ T cell receptor. Forty-five Variable (TRGV) genes belonging to the seven IMGT-NC validated mammalian TRGV subgroups, 25 Joining (TRGJ) and 17 Constant (TRGC) genes organized in 17 V-J-(J)-C cassettes, in tandem on about 1100 Kb, characterize the horse TRG locus, making the horse TRG locus the one with the greatest extension and with a significantly higher number of genes than the orthologous loci of the other mammalian species. A clonotype analysis of an RNA-seq transcriptomic dataset derived from spleen of an adult healthy horse, using the complete set of the horse TRGJ germline gene sequences as a probe, revealed that, in addition to the most prominent V-J rearrangements within each cassette, there is a relevant proportion of trans-cassette V-J recombination, whereby the same TRGV genes can recombine with different TRGJ genes spliced to the corresponding TRGC genes. This recombinant event strongly contributes to the diversity of the γ chain repertoire. In the donkey TRG locus, 34 TRGV, 21 TRGJ and 14 TRGC genes distributed in 14 V-J-(J)-C cassettes were found in a region of approximately 860 kb. Although the donkey's TRG is smaller than that of the horse, in genus, this is still the second largest locus so far found in any mammalian species. Finally, the comparative analysis highlighted differences in size and gene content between the horse and donkey TRG loci, despite belonging to the same genus, indicating a good level of diversification within . These data is in agreement with the evolutionary idea of the existence of a recent common ancestor in rapid evolution, for which a mutation rate between horses and donkeys is more comparable to that between species belonging to different genera rather than to species of the same genus.
Copyright © 2023 Massari, Giannico, Paolillo, Pala, Jambrenghi and Antonacci.
Publication Date: 2023-09-15 PubMed ID: 37781375PubMed Central: PMC10540303DOI: 10.3389/fimmu.2023.1264949Google Scholar: Lookup
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Summary
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The research explores the T cell receptor gamma (TRG) locus, responsible for encoding the gamma chain of the γδ T cell receptor, in two species of the Equus genus: horses and donkeys. The horses’ TRG locus has the greatest extension and significantly more genes than other mammals, contributing to the diversity of the γ chain repertoire. However, despite being of the same genus, the TRG loci of horses and donkeys showed noticeable differences in size and gene content.
Investigation of the T Cell Receptor Gamma Locus in the Horse and Donkey Genomes
- The research used the most recent genome assembly to study the T cell receptor gamma (TRG) locus in both horses and donkeys, an exploration that has never been done before. Frequently referred to as odd-toed ungulates, these species are part of the Equidae family and are characterized by an odd number of toes.
- In horses, the TRG locus spans around 1100 kilobases (Kb) and includes 45 Variable (TRGV), 25 Joining (TRGJ), and 17 Constant (TRGC) genes. These genes are sorted into 17 V-J-(J)-C cassettes. The size and gene content of the horse TRG locus make it the most extensive among other mammals’ orthologous loci.
- Analysis of transcriptomic data from the spleen of an adult horse showed a significant proportion of trans-cassette V-J recombination events, in which the same TRGV genes combine with varying TRGJ genes spliced to corresponding TRGC genes, contributing to the diversity of the γ chain repertoire.
Differences in the TRG Loci of Horses and Donkeys
- The TRG locus in the donkey’s genome is smaller than that of the horse, spanning approximately 860 kb. This locus encompasses 34 TRGV, 21 TRGJ, and 14 TRGC genes sorted into 14 V-J-(J)-C cassettes.
- While the donkey’s TRG locus is smaller, it remains the second-largest locus discovered in any mammalian species within the Equus genus.
Comparative Analysis Between Horse and Donkey TRG Loci
- Despite belonging to the same Equus genus, the TRG loci of horses and donkeys have noticeable differences in size and gene content.
- The difference suggests a high level of diversification within the Equus genus, in line with evolutionary hypothesis postulating a recent common ancestor rapidly evolving between horses and donkeys.
- This rapid evolution implies the mutation rate between horses and donkeys is more akin to that between species from different genera, not species within the same genus.
Cite This Article
APA
(2023).
Genomic and comparative analysis of the T cell receptor gamma locus in two Equus species.
Front Immunol, 14, 1264949.
https://doi.org/10.3389/fimmu.2023.1264949 Publication
Researcher Affiliations
MeSH Terms
- Horses / genetics
- Animals
- Amino Acid Sequence
- Genome
- Receptors, Antigen, T-Cell, gamma-delta / genetics
- Genomics
- Equidae / genetics
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
This article includes 45 references
- Lefranc M-P. Immunoglobulin (IG) and T cell receptor genes (TR): IMGT® and the birth and rise of immunoinformatics. Front Immunol 2014 5:22.
- Lefranc M-P, Lefranc G. The T Cell Receptor FactsBook. San Diego, CA, USA: Academic Press Harcourt Science and Technology Company; (2001).
- Gellert M. Molecular analysis of V(D)J recombination. Annu Rev Genet 1992 26:425–46.
- Gellert M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu Rev Biochem 2002 71:101–32.
- Jung D, Alt FW. Unraveling V(D)J recombination: insights into gene regulation. Cell 2004 116(2):299–311.
- Antonacci R, Massari S, Linguiti G, Jambrenghi AC, Giannico F, Lefranc M-P. Evolution of the T-cell receptor (TR) Loci in the adaptive immune response: The tale of the TRG locus in mammals. Genes 2020 11(6).
- Lefranc M-P, Rabbitts TH. The human T-cell receptor gamma (TRG) genes. Trends Biochem Sci 1989 14(6):214–8.
- Lefranc M-P, Chuchana P, Dariavach P, Nguyen C, Huck S, Brockly F. Molecular mapping of the human T cell receptor gamma (TRG) genes and linkage of the variable and constant regions. Eur J Immunol 1989 19:989–94.
- Lefranc M-P, Lefranc G. IMGT®Homo sapiens IG and TR loci, gene order, CNV and haplotypes: New concepts as a paradigm for jawed vertebrates genome assemblies. Biomolecules 2022 12(3):381.
- Lefranc M-P, Rabbitts TH. Two tandemly organized human genes encoding the T-cell gamma constant-region sequences show multiple rearrangement in different T-cell types. Nature 1985 316:464–6.
- Lefranc M-P, Forster A, Rabbitts TH. Rearrangement of two distinct T-cell gamma-chain variable-region genes in human DNA. Nature 1986 319:420–2.
- Lefranc M-P, Forster A, Rabbitts TH. Genetic polymorphism and exon changes of the constant regions of the human T-cell rearranging gene gamma. Proc Natl Acad Sci USA 1986 83:9596–600.
- Huck S, Lefranc M-P. Rearrangements to the JP1, JP and JP2 segments in the human T-cell rearranging gamma gene (TRGgamma) locus. FEBS Lett 1987 224:291–6.
- Lefranc M-P, Forster A, Baer R, Stinson MA, Rabbitts TH. Diversity and rearrangement of the human T cell rearranging gamma genes: Nine germ-line variable genes belonging to two subgroups. Cell 1986 45(2):237–46.
- Forster A, Huck S, Ghanem N, Lefranc M-P, Rabbitts TH. New subgroups in the human T cell rearranging Vgamma gene locus. EMBO J 1987 6:1945–50.
- Huck S, Dariavach P, Lefranc M-P. Variable region genes in the human T-cell rearranging gamma (TRG) locus: V-J junction and homology with the mouse genes. EMBO J 1988 7:719–26.
- Zhang XM, Tonnelle C, Lefranc M-P, Huck S. T cell receptor gamma cDNA in human fetal liver and thymus: Variable regions of gamma chains are restricted to VgammaI or V9, due to the absence of splicing of the V10 and V11 leader intron. Eur J Immunol 1994 24:571–8.
- Zhang XM, Cathala G, Soua Z, Lefranc M-P, Huck S. The human T-cell receptor gamma variable pseudogene V10 is a distinctive marker of human speciation. Immunogenetics 1996 43:196–203.
- Ghanem N, Buresi C, Moisan J-P, Bensmana M, Chuchana P, Huck S. Deletion, insertion, and restriction site polymorphism of the T-cell receptor gamma variable locus in French, Lebanese, Tunisian and Black African populations. Immunogenetics 1989 30:350–60.
- Ghanem N, Soua Z, Zhang XG, Zijun M, Zhiwei Y, Lefranc G. Polymorphism of the T-cell receptor gamma variable and constant region genes in a Chinese population. Hum Genet 1991 86:450–6.
- Buresi C, Ghanem N, Huck S, Lefranc G, Lefranc M-P. Exon duplication and triplication in the human T-cell receptor gamma constant region genes and RFLP in French, Lebanese, Tunisian, and Black African populations. Immunogenetics 1989 29:161–72.
- Massari S, Ciccarese S, Antonacci R. Structural and comparative analysis of the T cell receptor gamma (TRG) locus in Oryctolagus cuniculus. Immunogenetics 2012 64(10):773–9.
- Linguiti G, Antonacci R, Tasco G, Grande F, Casadio R, Massari S. Genomic and expression analyses of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) loci reveal a similar basic public γδ repertoire in dolphin and human. BMC Genomics 2016 17(1).
- Antonacci R, Linguiti G, Burger PA, Castelli V, Pala A, Fitak R. Comprehensive genomic analysis of the dromedary T cell receptor gamma (TRG) locus and identification of a functional TRGC5 cassette. Dev Comp Immunol 2020 106.
- Linguiti G, Giannico F, D’addabbo P, Pala A, Jambrenghi AC, Ciccarese S. The Organization of the Pig T-Cell Receptor γ (TRG) Locus Provides Insights into the Evolutionary Patterns of the TRG Genes across Cetartiodactyla. Genes 2022 13(2).
- Massari S, Lipsi MR, Vonghia G, Antonacci R, Ciccarese S. T-cell receptor TCRG1 and TCRG2 clusters map separately in two different regions of sheep chromosome 4. Chromosome Res 1998 6(5):419–20.
- Antonacci R, Vaccarelli G, Di Meo GP, Piccinni B, Miccoli MC, Cribiu EP. Molecular in situ hybridization analysis of sheep and goat BAC clones identifies the transcriptional orientation of T cell receptor gamma genes on chromosome 4 in bovids. Vet Res Commun 2007 31(8):977–83.
- Giannico F, Massari S, Caputi Jambrenghi A, Soriano A, Pala A, Linguiti G. The expansion of the TRB and TRG genes in domestic goats (Capra hircus) is characteristic of the ruminant species. BMC Genomics 2020 21(1).
- Massari S, Bellahcene F, Vaccarelli G, Carelli G, Mineccia M, Lefranc M-P. The deduced structure of the T cell receptor gamma locus in Canis lupus familiaris. Mol Immunol 2009 46(13):2728–36.
- Lefranc M-P. The mammalian T cell receptor gamma variable (TRGV) subgroups. IMGT Nomenclature (IMGT-NC) Report 200723. Berlin, Germany: ResearchGate; (2023).
- Lefranc M-P, Pommié C, Ruiz M, Giudicelli V, Foulquier E, Truong L. 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.
- Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 1987 4(4):406–25.
- Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 2018 35(6):1547–9.
- Stecher G, Tamura K, Kumar S. Molecular evolutionary genetics analysis (MEGA) for macOS. Mol Biol Evol 2020 37(4):1237–9.
- Nei M, Kumar S. Molecular Evolution and Phylogenetics. New York: Oxford University Press; (2000).
- Wang C, Li H, Guo Y, Huang J, Sun Y, Min J. Donkey genomes provide new insights into domestication and selection for coat color. Nat Commun 2020 11:6014.
- Trifonov VA, Musilova P, Kulemsina AI. Chromosome evolution in perissodactyla. Cytogenet Genome Res 2012 137(2-4):208–17.
- Orlando L, Ginolhac A, Zhang G, Froese D, Albrechtsen A, Stiller M. Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse. Nature 2013 499(7456):74–8.
- Cirilli O, Pandolfi L, Rook L, Bernor RL. Evolution of Old World Equus and origin of the zebra-ass clade. Sci Rep 2021 11(1).
- Bininda-Emonds OR, Cardillo M, Jones KE, MacPhee RD, Beck RM, Grenyer R. The delayed rise of presentday mammals. Nature 2007 446:507–12.
- Le Page L, Gillespie A, Schwartz JC, Prawits L-, Schlerka A, Farrell CP. Subpopulations of swine γδ T cells defined by TCRγ and WC1 gene expression. Dev Comp Immunol 2021 125.
- Giudicelli V, Chaume D, Lefranc M-P. IMGT/GENE-DB: A comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res 2005 33(DATABASE ISS.):D256–61.
- Zhang Z, Hernandez K, Savage J, Li S, Miller D, Agrawal S. Uniform genomic data analysis in the NCI Genomic Data Commons. Nat Commun 2021 12:1226.
- Edgar RC. MUSCLE: A multiple sequence alignment method with reduced time and space complexity. BMC Bioinform 2004 5.
- Lefranc M-P, Pommié C, Kaas Q, Duprat E, Bosc N, Guiraudou D. IMGT unique numbering for immunoglobulin and T cell receptor constant domains and ig superfamily c-like domains. Dev Comp Immunol 2005 29:185–203.
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