- Diego Garzón-Ospina ORCID:orcid.org/0000-0003-3829-67191,2,3 &
- Sindy P. Buitrago ORCID:orcid.org/0000-0002-9872-56611,2,3
352Accesses
7Citations
Abstract
Immunoglobulin G (IgG) is one of the five antibody classes produced in mammals as part of the humoral responses accountable for protecting the organisms from infection. Its antibody heavy chain constant region is encoded by the Ig heavy-chain gamma gene (IGHG). In humans, there are fourIGHG genes which encode the four subclasses, each with a specialized effector function. Although four subclasses of IgG proteins have also been reported in macaques, this does not appear to be the rule for all primates. In Platyrrhini, IgG has been stated to be encoded by a single-copy gene. To date, it remains unknown how theIGHG has expanded or contracted in the primate order; consequently, we have analyzed data from 38 primate genome sequences to identifyIGHG genes and describe the evolution ofIGHG genes in primate order.IGHG belongs to a multigene family that evolves by the birth–death evolutionary model in primates. Whereas Strepsirrhini and Platyrrhini have a single-copy gene, in Catarrhini, it has expanded to several paralogs in their genomes; some deleted and others pseudogenized. Furthermore, episodic positive selection may have promoted a species-specific IgG effector function. We propose that IgG evolved to reach an optimal number of copies per genome to adapt their humoral immune responses to different environmental conditions. This study has implications for biomedical trials using non-human primates.
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The datasets supporting this article’s results are available in Mendeley Data,https://doi.org/10.17632/r6vh2rfnts.1.
Abbreviations
- Alpa :
Alouatta palliate
- Aona :
Aotus nancymaae
- Atge :
Ateles geoffroyi
- Caja :
Callithrix jacchus
- Ceal :
Cebus albifrons
- Ceca :
Cebus capucinus
- Ceat :
Cercocebus atys
- Erpa :
Erythrocebus patas
- Eufl :
Eulemur flavifrons
- Eufu :
Eulemur fulvus
- Euma :
Eulemur macaco
- Gogo :
Gorilla gorilla
- Hosa :
Homo sapiens
- Inin :
Indri indri
- Mafu :
Macaca fuscata
- Mamu :
Macaca mulatta
- Mane :
Macaca, nemestrina
- Masp :
Mandrillus sphinx
- Migr :
Microcebus griseorufus
- Mimi :
Microcebus mittermeieri
- Mimu :
Microcebus murines
- Mira :
Microcebus ravelobensis
- Mita :
Microcebus tavaratra
- Miza :
Mirza zaza
- Nala :
Nasalis larvatus
- Patr :
Pan troglodytes
- Pipi :
Pithecia pithecia
- Pldo :
Plecturocebus donacophilus
- Poab :
Pongo abelii
- Prsi :
Prolemur simus
- Prco :
Propithecus coquereli
- Pyne :
Pygathrix nemaeus
- Rhro :
Rhinopithecus roxellana
- Saim :
Saguinus imperator
- Sabo :
Saimiri boliviensis
- Saap :
Sapajus paella
- Thge :
Theropithecus gelada
- Trfr :
Trachypithecus francoisi
References
Abascal F, Zardoya R, Telford MJ (2010) TranslatorX: multiple alignment of nucleotide sequences guided by amino acid translations. Nucleic Acids Res 38:W7-13.https://doi.org/10.1093/nar/gkq291
Anisimova M, Nielsen R, Yang Z (2003) Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites. Genetics 164:1229–1236
Arenas M, Posada D (2010) Coalescent simulation of intracodon recombination. Genetics 184:429–437.https://doi.org/10.1534/genetics.109.109736
Arenas M, Posada D (2014) The influence of recombination on the estimation of selection from coding sequence alignments. In: Fares MA (ed) Natural selection: methods and applications. CRC Press/Taylor & Francis, Boca Raton
Asada Y, Kawamoto Y, Shotaki T, Terao K (2002) Molecular evolution of IgG subclass among nonhuman primates: implication of differences in antigenic determinants among apes. Primates 43:343–349.https://doi.org/10.1007/BF02629608
Birdsall HH (2015) 5—adaptive immunity: antibodies and immunodeficiencies. In: Bennett JE, Dolin R, Blaser MJ (eds) Mandell, douglas, and bennett’s principles and practice of infectious diseases, 8th edn. Content Repository Only!, Philadelphia
Brusco A, Cinque F, Saviozzi S, Boccazzi C, DeMarchi M, Carbonara AO (1997) The G4 gene is duplicated in 44% of human immunoglobulin heavy chain constant region haplotypes. Hum Genet 100:84–89.https://doi.org/10.1007/s004390050470
Brusco A, Carbonara AO, Crovella S, Bottaro A (1998) Primate immunoglobulin heavy chain constant gamma genes: an hypothesis of their evolution. Hum Evol 13:49–56.https://doi.org/10.1007/BF02439368
Crowley AR, Ackerman ME (2019) Mind the gap: how interspecies variability in igg and its receptors may complicate comparisons of human and non-human primate effector function. Front Immunol 10:697.https://doi.org/10.3389/fimmu.2019.00697
Darriba D, Taboada GL, Doallo R, Posada D (2011) ProtTest 3: fast selection of best-fit models of protein evolution. Bioinformatics 27:1164–1165.https://doi.org/10.1093/bioinformatics/btr088
Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:214
Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acid Res 32(5):1792–1797.https://doi.org/10.1093/nar/gkh340
El-Gebali S, Mistry J, Bateman A, Eddy SR, Luciani A, Potter SC, Qureshi M, Richardson LJ, Salazar GA, Smart A, Sonnhammer ELL, Hirsh L, Paladin L, Piovesan D, Tosatto SCE, Finn RD (2019) The Pfam protein families database in 2019. Nucleic Acids Res 47:D427–D432.https://doi.org/10.1093/nar/gky995
Esteves MB, Binaghi RA (1972) Antigenic similarities among mammalian immunoglobulins. Immunology 23:137–145
Fay JC, Wu CI (2003) Sequence divergence, functional constraint, and selection in protein evolution. Annu Rev Genomics Hum Genet 4:213–235.https://doi.org/10.1146/annurev.genom.4.020303.162528
Flanagan JG, Rabbitts TH (1982) Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes. Nature 300:709–713.https://doi.org/10.1038/300709a0
Garzon-Ospina D, Buitrago SP (2020) Igh locus structure and evolution in Platyrrhines: new insights from a genomic perspective. Immunogenetics 72:165–179.https://doi.org/10.1007/s00251-019-01151-8
Garzon-Ospina D, Cadavid LF, Patarroyo MA (2010) Differential expansion of the merozoite surface protein (msp)-7 gene family inPlasmodium species under a birth-and-death model of evolution. Mol Phylogenet Evol 55:399–408.https://doi.org/10.1016/j.ympev.2010.02.017
Gu X (2003) Functional divergence in protein (family) sequence evolution. Genetica 118:133–141
Hood JM, Huang HV, Hood L (1980) A computer simulation of evolutionary forces controlling the size of a multigene family. J Mol Evol 15:181–196.https://doi.org/10.1007/BF01732947
Huelsenbeck JP, Ronquist F, Nielsen R, Bollback JP (2001) Bayesian inference of phylogeny and its impact on evolutionary biology. Science 294:2310–2314.https://doi.org/10.1126/science.1065889
Hughes AL, Nei M (1990) Evolutionary relationships of class II major-histocompatibility-complex genes in mammals. Mol Biol Evol 7:491–514.https://doi.org/10.1093/oxfordjournals.molbev.a040622
Idusogie EE, Wong PY, Presta LG, Gazzano-Santoro H, Totpal K, Ultsch M, Mulkerrin MG (2001) Engineered antibodies with increased activity to recruit complement. J Immunol 166:2571–2575.https://doi.org/10.4049/jimmunol.166.4.2571
Irani V, Guy AJ, Andrew D, Beeson JG, Ramsland PA, Richards JS (2015) Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases. Mol Immunol 67:171–182.https://doi.org/10.1016/j.molimm.2015.03.255
Jacobsen FW, Padaki R, Morris AE, Aldrich TL, Armitage RJ, Allen MJ, Lavallee JC, Arora T (2011) Molecular and functional characterization of cynomolgus monkey IgG subclasses. J Immunol 186:341–349.https://doi.org/10.4049/jimmunol.1001685
Kondrashov FA, Kondrashov AS (2006) Role of selection in fixation of gene duplications. J Theor Biol 239:141–151.https://doi.org/10.1016/j.jtbi.2005.08.033
Kondrashov FA, Rogozin IB, Wolf YI, Koonin EV (2002) Selection in the evolution of gene duplications. Genome Biol.https://doi.org/10.1186/gb-2002-3-2-research0008
Kosakovsky Pond SL, Frost SD (2005) Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22:1208–1222.https://doi.org/10.1093/molbev/msi105
Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SD (2006) Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23:1891–901
Krakauer DC, Nowak MA (1999) Evolutionary preservation of redundant duplicated genes. Semin Cell Dev Biol 10:555–559.https://doi.org/10.1006/scdb.1999.0337
Kumar S, Stecher G, Suleski M, Hedges SB (2017) timetree: a resource for timelines, timetrees, and divergence times. Mol Biol Evol 34:1812–1819.https://doi.org/10.1093/molbev/msx116
Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290:1151–1155.https://doi.org/10.1126/science.290.5494.1151
Messier W, Stewart CB (1997) Episodic adaptive evolution of primate lysozymes. Nature 385:151–154.https://doi.org/10.1038/385151a0
Miller MA, PW, Schwartz T (2010) Creating the CIPRES Science Gateway for inference of large phylogenetic trees. Proceedings of the Gateway Computing Environments Workshop (GCE). New Orleans, LA.p. 1–8
Miller MA, Schwartz T, Pickett BE, He S, Klem EB, Scheuermann RH, Passarotti M, Kaufman S, O’Leary MA (2015) A RESTful API for access to phylogenetic tools via the CIPRES science gateway. Evol Bioinform Online 11:43–48.https://doi.org/10.4137/EBO.S21501
Mishra R, Panda SK, Sahoo PK, Mishra S, Satapathy AK (2019) Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis. Cell Immunol 341:103927.https://doi.org/10.1016/j.cellimm.2019.103927
Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Kosakovsky Pond SL (2012) Detecting individual sites subject to episodic diversifying selection. PLoS Genet 8:e1002764.https://doi.org/10.1371/journal.pgen.1002764
Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL, Scheffler K (2013) FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol Biol Evol 30:1196–1205.https://doi.org/10.1093/molbev/mst030
Napodano C, Marino M, Stefanile A, Pocino K, Scatena R, Gulli F, Rapaccini GL, Delli Noci S, Capozio G, Rigante D, Basile U (2020) Immunological role of IgG subclasses. Immunol Invest.https://doi.org/10.1080/08820139.2020.1775643
Nei M, Rooney AP (2005) Concerted and birth-and-death evolution of multigene families. Annu Rev Genet 39:121–152.https://doi.org/10.1146/annurev.genet.39.073003.112240
Nei M, Gu X, Sitnikova T (1997) Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci USA 94:7799–7806.https://doi.org/10.1073/pnas.94.15.7799
Newcomb RD, Campbell PM, Ollis DL, Cheah E, Russell RJ, Oakeshott JG (1997) A single amino acid substitution converts a carboxylesterase to an organophosphorus hydrolase and confers insecticide resistance on a blowfly. Proc Natl Acad Sci USA 94:7464–7468.https://doi.org/10.1073/pnas.94.14.7464
Nguyen DC, Sanghvi R, Scinicariello F, Pulit-Penaloza J, Hill N, Attanasio R (2014) Cynomolgus and pigtail macaque IgG subclasses: characterization ofIGHG genes and computational analysis of IgG/Fc receptor binding affinity. Immunogenetics 66:361–377.https://doi.org/10.1007/s00251-014-0775-4
Nicholas K, Nicholas H (1997) GeneDoc: A tool for editing and annotating multiple sequence alignments. EMBNEW.NEWS 4:14.http://nrbsc.org/gfx/genedoc/
Nimmerjahn F, Ravetch JV (2005) Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310:1510–1512.https://doi.org/10.1126/science.1118948
Olivieri DN, Gambon Deza F (2018) Immunoglobulin genes in primates. Mol Immunol 101:353–363.https://doi.org/10.1016/j.molimm.2018.07.020
Ota T, Nei M (1994) Divergent evolution and evolution by the birth-and-death process in the immunoglobulin VH gene family. Mol Biol Evol 11:469–482.https://doi.org/10.1093/oxfordjournals.molbev.a040127
Parra-Montano JD, Mateus-Rincon KC, Aranguren-Borras JV, Medrano-Robayo M, Figueredo-Lopez A, Gonzalez-Amaya LM, Vega-Valderrama JD, Gonzalez-Bautista LF, Becerra-Embus AL, Aponte-Rubio Y, Alfonso-Gonzalez H, Buitrago SP, Garzon-Ospina D (2022) IgG subclasses in New World Monkeys: an issue for debate? Immunogenetics.https://doi.org/10.1007/s00251-022-01266-5
Perutz MF (1984) Species adaptation in a protein molecule. Adv Protein Chem 36:213–244.https://doi.org/10.1016/s0065-3233(08)60298-3
Posada D (2008) jModelTest: phylogenetic model averaging. Mol Biol Evol 25:1253–1256.https://doi.org/10.1093/molbev/msn083
Rambaut A, Drummond AJ, Xie D, Baele G, Suchard MA (2018) Posterior summarization in bayesian phylogenetics using tracer 1.7. Syst Biol 67:901–904.https://doi.org/10.1093/sysbio/syy032
Ramesh A, Darko S, Hua A, Overman G, Ransier A, Francica JR, Trama A, Tomaras GD, Haynes BF, Douek DC, Kepler TB (2017) Structure and diversity of the rhesus macaque immunoglobulin loci through multiple de novo genome assemblies. Front Immunol 8:1407.https://doi.org/10.3389/fimmu.2017.01407
Schroeder HW Jr, Cavacini L (2010) Structure and function of immunoglobulins. J Allergy Clin Immunol 125:S41-52.https://doi.org/10.1016/j.jaci.2009.09.046
Schur PH (1987) IgG subclasses—a review. Ann Allergy 58(89–96):99
Senger K, Hackney J, Payandeh J, Zarrin AA (2015) Antibody isotype switching in vertebrates. Results Probl Cell Differ 57:295–324.https://doi.org/10.1007/978-3-319-20819-0_13
Sjostrand J, Sennblad B, Arvestad L, Lagergren J (2012) DLRS: gene tree evolution in light of a species tree. Bioinformatics 28:2994–2995.https://doi.org/10.1093/bioinformatics/bts548
Sjostrand J, Tofigh A, Daubin V, Arvestad L, Sennblad B, Lagergren J (2014) A Bayesian method for analyzing lateral gene transfer. Syst Biol 63:409–420.https://doi.org/10.1093/sysbio/syu007
Smith MD, Wertheim JO, Weaver S, Murrell B, Scheffler K, Kosakovsky Pond SL (2015) Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection. Mol Biol Evol 32:1342–1353.https://doi.org/10.1093/molbev/msv022
Solovyev VV (2007) Statistical approaches in Eukaryotic gene prediction. In: Balding D, Cannings C, Bishop M (eds) Handbook of statistical genetics, 3rd edn. Wiley-Interscience, p 1616
Stephens SG (1951) Possible significances of duplication in evolution. Adv Genet 4:247–265.https://doi.org/10.1016/s0065-2660(08)60237-0
Su C, Nei M (2001) Evolutionary dynamics of the T-cell receptor VB gene family as inferred from the human and mouse genomic sequences. Mol Biol Evol 18:503–513.https://doi.org/10.1093/oxfordjournals.molbev.a003829
Suchard MA, Lemey P, Baele G, Ayres DL, Drummond AJ, Rambaut A (2018) Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol.https://doi.org/10.1093/ve/vey016
Sun Y, Liu Z, Ren L, Wei Z, Wang P, Li N, Zhao Y (2012) Immunoglobulin genes and diversity: what we have learned from domestic animals. J Anim Sci Biotechnol 3:18.https://doi.org/10.1186/2049-1891-3-18
Takahashi N, Ueda S, Obata M, Nikaido T, Nakai S, Honjo T (1982) Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Cell 29:671–679.https://doi.org/10.1016/0092-8674(82)90183-0
Tamura K, Battistuzzi FU, Billing-Ross P, Murillo O, Filipski A, Kumar S (2012) Estimating divergence times in large molecular phylogenies. Proc Natl Acad Sci USA 109:19333–19338.https://doi.org/10.1073/pnas.1213199109
Tamura K, Tao Q, Kumar S (2018) Theoretical foundation of the reltime method for estimating divergence times from variable evolutionary rates. Mol Biol Evol 35:1770–1782.https://doi.org/10.1093/molbev/msy044
Tamura K, Stecher G, Kumar S (2021) MEGA11: molecular evolutionary genetics analysis version 11. Mol Biol Evol 38:3022–3027.https://doi.org/10.1093/molbev/msab120
Tao Q, Tamura K, Mello B, Kumar S (2020) Reliable confidence intervals for reltime estimates of evolutionary divergence times. Mol Biol Evol 37:280–290.https://doi.org/10.1093/molbev/msz236
Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520.https://doi.org/10.3389/fimmu.2014.00520
Warncke M, Calzascia T, Coulot M, Balke N, Touil R, Kolbinger F, Heusser C (2012) Different adaptations of IgG effector function in human and nonhuman primates and implications for therapeutic antibody treatment. J Immunol 188:4405–4411.https://doi.org/10.4049/jimmunol.1200090
Weaver S, Shank SD, Spielman SJ, Li M, Muse SV, Kosakovsky Pond SL (2018) Datamonkey 2.0: a modern web application for characterizing selective and other evolutionary processes. Mol Biol Evol.https://doi.org/10.1093/molbev/msx335
Wertheim JO, Murrell B, Smith MD, Kosakovsky Pond SL, Scheffler K (2015) RELAX: detecting relaxed selection in a phylogenetic framework. Mol Biol Evol 32:820–832.https://doi.org/10.1093/molbev/msu400
Woof JM, Burton DR (2004) Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol 4:89–99.https://doi.org/10.1038/nri1266
Zhang J (2003) Evolution by gene duplication: an update. Trends Ecol Evol 18:292–298.https://doi.org/10.1016/S0169-5347(03)00033-8
Zhang J, Rosenberg HF, Nei M (1998) Positive Darwinian selection after gene duplication in primate ribonuclease genes. Proc Natl Acad Sci USA 95:3708–3713.https://doi.org/10.1073/pnas.95.7.3708
Acknowledgements
The authors wish to thank Gypsy Bonny Español for reviewing the manuscript.
Funding
This work was supported by the Fundación para la Promoción de la Investigación y la Tecnología [cooperation agreement #202111, 2021].
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Authors and Affiliations
PGAME-Population Genetics and Molecular Evolution, Fundación Scient, Tunja, Boyacá, Colombia
Diego Garzón-Ospina & Sindy P. Buitrago
GEBIMOL, School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia-UPTC, Tunja, Boyacá, Colombia
Diego Garzón-Ospina & Sindy P. Buitrago
GEO, School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia-UPTC, Tunja, Boyacá, Colombia
Diego Garzón-Ospina & Sindy P. Buitrago
- Diego Garzón-Ospina
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- Sindy P. Buitrago
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DG-O: Conceptualization, Investigation, Formal analysis, Methodology, Visualization, Writing—Original draft preparation, Acquiring funding. SPB: Investigation, Methodology, Visualization, Formal analysis, Writing—Reviewing and Editing.
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Correspondence toDiego Garzón-Ospina orSindy P. Buitrago.
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10329_2022_1019_MOESM3_ESM.tif
Supplementary file3 (TIF 1583 kb) Four major clades were identified clustering DNA sequences in agreement with primate phylogenetic relationships. The branching pattern shows posterior probabilities higher than > 0.95 (numbers on branches) supporting the topology. Purple clade cluster the StrepsirrhiniIGHG gene sequences; red clade put together Platyrrhini genes; yellow clade group Cercopithecoidea paralogs and the clade clusteringIGHG duplicates from Hominoidea are depicted in blue
10329_2022_1019_MOESM4_ESM.tif
Supplementary file4 (TIF 2059 kb) Four major clades were identified clustering amino acid sequences in agreement with primate phylogenetic relationships. The branching pattern shows posterior probabilities higher than > 0.95 (numbers on branches) supporting the topology. Purple clade cluster the Strepsirrhini IgG protein sequences; red clade put together Platyrrhini genes; yellow clade group Cercopithecoidea paralogs and the clade clusteringIGHG duplicates from Hominoidea are depicted in blue
10329_2022_1019_MOESM5_ESM.tif
Supplementary file5 (TIF 2270 kb) IgG tree inferred by evolving down the species tree. Numbers on branches are posterior probability values. Purple clade cluster the Strepsirrhini IgG protein sequences; red clade put together Platyrrhini genes; yellow clade group Cercopithecoidea paralogs and the clade clusteringIGHG duplicates from Hominoidea are depicted in blue. Both BY and DLTRS trees showed similar topologies using DNA or proteins sequences
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Garzón-Ospina, D., Buitrago, S.P. Immunoglobulin heavy constant gamma gene evolution is modulated by both the divergent and birth-and-death evolutionary models.Primates63, 611–625 (2022). https://doi.org/10.1007/s10329-022-01019-8
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