Hymenopteran insects are infamous for their sting, and their ability to cause severe anaphylaxis and in some cases death. This allergic reaction is a result of allergens present in the venom. Hymenopterans have many common venom allergens, the most widespread of which include phospholipase A1, phospholipase A2, acid phosphatase, hyaluronidase, serine protease and antigen 5. While there have been studies that look at the phylogenetic histories of allergens within closely related species, to our knowledge, this is the first study using evolutionary analyses to compare across Hymenoptera the types of selection that are occurring on allergens. This research examined the publicly available sequences of six different groups of allergens and found that allergens had diverged and formed closely related clades which share greater sequence similarities. We also analysed the patterns of selection and found that they are predominately under the influence of negative selection.
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Basheer AR, El-Asmar MF, Soslau G (1995) Characterization of a potent platelet aggregation inducer from Cerastes cerastes (Egyptian sand viper) venom. Biochimica et Biophysica Acta (BBA) (Protein Struct Mol Enzymol) 1250(1):97–109
Bateman A, O’Donovan C, Magrane M, Alpi E, Antunes R, Bely B et al (2018) UniProt: the universal protein knowledgebase. Nucleic Acids Res 45:D1
Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL (2006) GenBank. Nucleic Acids Res 34(Database issue):D16–D20
Bilò MB (2011) Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment. Allergy 66(Suppl 9):35–37
Bircher AJ (2005) Systemic immediate allergic reactions to arthropod stings and bites. Dermatology 210(2):119–127
Brust A, Sunagar K, Undheim EAB, Vetter I, Yang DC, Yang DC et al (2013) Differential evolution and neofunctionalization of snake venom metalloprotease domains. Mol Cell Proteomics 12(3):651–663
Casewell NR, Wagstaff SC, Harrison RA, Renjifo C, Wuster W (2011) Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes. Mol Biol Evol 28(9):2637–2649
Casewell NR, Huttley GA, Wüster W (2012) Dynamic evolution of venom proteins in squamate reptiles. Nat Commun 3(1):1066–1066
Dunlop JA, Selden PA (2009) Calibrating the chelicerate clock: a paleontological reply to Jeyaprakash and Hoy. Exp Appl Acarol 48(3):183–197
Dutertre S, Jin A-H, Vetter I, Hamilton B, Sunagar K, Lavergne V et al (2014) Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun 5:3521–3521
Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32(5):1792–1797
Fry BG, Roelants K, Champagne DE, Scheib H, Tyndall JDA, King GF et al (2009) The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genomics Hum Genet 10:483–511
Grimaldi DA, Engel MS (2005) Evolution of the insects. Cambridge University Press, Cambridge
Harrison RA, Ibison F, Wilbraham D, Wagstaff SC (2007) Identification of cDNAs encoding viper venom hyaluronidases: cross-generic sequence conservation of full-length and unusually short variant transcripts. Gene 392(1–2):22–33
Henriksen A, King TP, Mirza O, Monsalve RlI, Meno Kr, Ipsen H et al (2001) Major venom allergen of yellow jackets, Ves v 5: structural characterization of a pathogenesis-related protein superfamily. Proteins Struct Funct Genet 45(4):438–448
Hoffman DR (2006) Hymenoptera venom allergens. Clin Rev Allergy Immunol 30(2):109–128
Hoffman DR (2008) Structural biology of allergens from stinging and biting insects. Curr Opin Allergy Clin Immunol 8(4):338–342
Jouiaei M, Sunagar K, Gross AF, Scheib H, Alewood PF, Moran Y, Fry BG (2015) Evolution of an ancient venom: recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone. Mol Biol Evol 32:1598–1610
Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10(6):845–858
King TP, Wittkowski KM (2011) Hyaluronidase and hyaluronan in insect venom allergy. Int Arch Allergy Immunol 156(2):205–211
Larsson A (2014) AliView: a fast and lightweight alignment viewer and editor for large datasets. Bioinformatics 30(22):3276–3278
Lynch VJ (2007) Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A 2 genes. BMC Evol Biol 7(1):2–2
Mirza O, Henriksen A, Ipsen H, Larsen JN, Wissenbach M, Spangfort MD, Gajhede M (2000) Dominant epitopes and allergic cross-reactivity: complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1. J Immunol (Baltimore Md: 1950) 165(1):331–338
Murayama N, Saguchi Ki, Mentele R, Assakura MT, Ohi H, Fujita Y et al (2003) The unusual high molecular mass of Bothrops protease A, a trypsin-like serine peptidase from the venom of Bothrops jararaca, is due to its high carbohydrate content. Biochimica et biophysica acta 1652(1):1–6
Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Pond K, S. L (2012) Detecting individual sites subject to episodic diversifying selection. PLoS Genet 8(7):e1002764
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(5):1196–1205
Palma MS (2013) Handbook of biologically active peptides, 2nd edn. Elsevier, New York
Park E, Hwang D-S, Lee J-S, Song J-I, Seo T-K, Won Y-J (2012) Estimation of divergence times in cnidarian evolution based on mitochondrial protein-coding genes and the fossil record. Mol Phylogenet Evol 62(1):329–345
Peters RS, Krogmann L, Mayer C, Donath A, Gunkel S, Meusemann K et al (2017) Evolutionary history of the Hymenoptera. Curr Biol 27(7):1013–1018
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera: a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612
Pond SK, Muse SV (2005) Site-to-site variation of synonymous substitution rates. Mol Biol Evol 22(12):2375–2385
Radauer C, Bublin M, Wagner S, Mari A, Breiteneder H (2008) Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J Allergy Clin Immunol 121(4):847–852.e847
Ronquist F, Teslenko M, van der Mark P, Ayres DL, Darling A, Höhna S et al (2012) MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space. Syst Biol 61(3):539–542
Ruder T, Sunagar K, Undheim EAB, Ali SA, Wai T-C, Low DHW et al (2013) Molecular phylogeny and evolution of the proteins encoded by coleoid (cuttlefish, octopus, and squid) posterior venom glands. J Mol Evol 76(4):192–204
Schmidt JO (2009) Defensive behavior, Elsevier, New York, pp 252–257
Sunagar K, Moran Y (2015) The rise and fall of an evolutionary innovation: contrasting strategies of venom evolution in ancient and young animals. PLoS Genet 11(10):e1005596
Sunagar K, Johnson WE, O’Brien SJ, Vasconcelos V, Antunes A (2012) Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction. Mol Biol Evol 29(7):1807–1822
Sunagar K, Fry BG, Jackson TNW, Casewell NR, Undheim EAB, Vidal N et al (2013a) Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf. PLoS ONE 8(11):e81827–e81827
Sunagar K, Jackson TNW, Undheim EAB, Ali SA, Antunes A, Fry BG (2013b) Three-fingered RAVERs: rapid accumulation of variations in exposed residues of snake venom toxins. Toxins 5(11):2172–2208
Sunagar K, Undheim EAB, Chan AHC, Koludarov I, Muñoz-Gómez SA, Antunes A, Fry BG (2013c) Evolution stings: the origin and diversification of scorpion toxin peptide scaffolds. Toxins 5(12):2456–2487
Sunagar K, Undheim EaB, Scheib H, Gren ECK, Cochran C, Person CE et al (2014) Intraspecific venom variation in the medically significant Southern Pacific Rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary implications. J Proteomics 99:68–83
Suzuki N, Yamazaki Y, Fujimoto Z, Morita T, Mizuno H (2005) Crystallization and preliminary X-ray diffraction analyses of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels. Acta Crystallogr F 61(Pt 8):750–752
Tsai I-H, Tsai H-Y, Wang Y-M, Tun P, Warrell DA (2007) Venom phospholipases of Russell’s vipers from Myanmar and eastern India—Cloning, characterization and phylogeographic analysis. Biochimica et Biophysica Acta (BBA) (Proteins Proteomics) 1774(8):1020–1028
Yamazaki Y, Brown RL, Morita T (2002) Purification and cloning of toxins from elapid venoms that target cyclic nucleotide-gated ion channels. Biochemistry 41(38):11331–11337
KB and DB were supported by University of Queensland PhD scholarships. This work was also supported by the Department of Science and Technology (DST) INSPIRE Faculty Award (DST/INSPIRE/04/2017/000071) to KS and the DBT-IISc Partnership Program.
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Baumann, K., Dashevsky, D., Sunagar, K. et al. Scratching the Surface of an Itch: Molecular Evolution of Aculeata Venom Allergens. J Mol Evol 86, 484–500 (2018). https://doi.org/10.1007/s00239-018-9860-x
- Venom evolution