#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals


While the influence of positive selection in diversifying animal venoms is widely recognized, the role of purifying selection that conserves the amino acid sequence of venom components such as peptide toxins has never been considered. In addition to unraveling the unique strategies of evolution of toxin gene families in centipedes and spiders, which are amongst the first terrestrial venomous lineages, we highlight the significant role of purifying selection in shaping the composition of animal venoms. Analysis of numerous toxin families, spanning the breadth of the animal kingdom, has revealed a striking contrast between the evolution of venom in ancient and evolutionarily young animal groups. Our findings enable the postulation of a new theory of venom evolution. The proposed ‘two-speed’ mode of evolution of venom captures the fascinating evolutionary history and the dynamics of this complex biochemical cocktail.


Vyšlo v časopise: The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005596
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005596

Souhrn

While the influence of positive selection in diversifying animal venoms is widely recognized, the role of purifying selection that conserves the amino acid sequence of venom components such as peptide toxins has never been considered. In addition to unraveling the unique strategies of evolution of toxin gene families in centipedes and spiders, which are amongst the first terrestrial venomous lineages, we highlight the significant role of purifying selection in shaping the composition of animal venoms. Analysis of numerous toxin families, spanning the breadth of the animal kingdom, has revealed a striking contrast between the evolution of venom in ancient and evolutionarily young animal groups. Our findings enable the postulation of a new theory of venom evolution. The proposed ‘two-speed’ mode of evolution of venom captures the fascinating evolutionary history and the dynamics of this complex biochemical cocktail.


Zdroje

1. Vidal N, Rage J, Couloux A, Hedges SB. Snakes (Serpentes) in The Timetree of Life, Hedges S. B. and Kumar S., Eds. Oxford University Press. 2009:390–7.

2. Olivera BM. E.E. Just Lecture, 1996. Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology. Molecular biology of the cell. 1997;8(11):2101–9. 9362055; PubMed Central PMCID: PMC25694.

3. Duda TF Jr., Kohn AJ. Species-level phylogeography and evolutionary history of the hyperdiverse marine gastropod genus Conus. Mol Phylogenet Evol. 2005;34(2):257–72. doi: 10.1016/j.ympev.2004.09.012 15619440.

4. Chang D, Duda TF Jr. Extensive and continuous duplication facilitates rapid evolution and diversification of gene families. Mol Biol Evol. 2012;29(8):2019–29. doi: 10.1093/molbev/mss068 22337864.

5. Wong ES, Belov K. Venom evolution through gene duplications. Gene. 2012;496(1):1–7. Epub 2012/01/31. doi: 10.1016/j.gene.2012.01.009 22285376.

6. Sunagar K, Johnson WE, O'Brien SJ, Vasconcelos V, Antunes A. Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction. Mol Biol Evol. 2012;29(7):1807–22. doi: 10.1093/molbev/mss058 22319140.

7. Dutertre S, Jin AH, Vetter I, Hamilton B, Sunagar K, Lavergne V, et al. Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nature communications. 2014;5:3521. doi: 10.1038/ncomms4521 24662800; PubMed Central PMCID: PMC3973120.

8. Casewell NR, Wagstaff SC, Harrison RA, Renjifo C, Wuster W. Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes. Molecular biology and evolution. 2011;28(9):2637–49. doi: 10.1093/molbev/msr091 21478373.

9. Nakashima K, Ogawa T, Oda N, Hattori M, Sakaki Y, Kihara H, et al. Accelerated evolution of Trimeresurus flavoviridis venom gland phospholipase A2 isozymes. Proceedings of the National Academy of Sciences of the United States of America. 1993;90(13):5964–8. Epub 1993/07/01. 8327468; PubMed Central PMCID: PMCPmc46847.

10. Duda TF Jr., Palumbi SR. Molecular genetics of ecological diversification: duplication and rapid evolution of toxin genes of the venomous gastropod Conus. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(12):6820–3. Epub 1999/06/09. 10359796; PubMed Central PMCID: PMCPmc21999.

11. Waddington J, Rudkin DM, Dunlop JA. A new mid-Silurian aquatic scorpion-one step closer to land? Biology letters. 2015;11(1). Epub 2015/01/16. doi: 10.1098/rsbl.2014.0815 25589484.

12. Quintero-Hernández V, Jiménez-Vargas JM, Gurrola GB, Valdivia HH, Possani LD. Scorpion venom components that affect ion-channels function. Toxicon: official journal of the International Society on Toxinology. 2013;76(0):328–42. doi: http://dx.doi.org/10.1016/j.toxicon.2013.07.012

13. Erwin DH, Laflamme M, Tweedt SM, Sperling EA, Pisani D, Peterson KJ. The Cambrian conundrum: early divergence and later ecological success in the early history of animals. Science. 2011;334(6059):1091–7. Epub 2011/11/26. doi: 10.1126/science.1206375 22116879.

14. Park E, Hwang DS, Lee JS, Song JI, Seo TK, Won YJ. Estimation of divergence times in cnidarian evolution based on mitochondrial protein-coding genes and the fossil record. Molecular phylogenetics and evolution. 2012;62(1):329–45. Epub 2011/11/02. doi: 10.1016/j.ympev.2011.10.008 22040765.

15. Menon LR, McIlroy D, Brasier MD. Evidence for Cnidaria-like behavior in ca. 560 Ma Ediacaran Aspidella. Geology. 2013. doi: 10.1130/g34424.1

16. Sturmer W. A small coleoid cephalopod with soft parts from the lower Devonian discovered using radiography. Nature. 1985;318(6041):53–5.

17. Lo Bianco S. Notizie biologiche riguardanti specialmente il periodo di maturita sessuale degli animali del Golfo di Napoli. Mitth Zool Stat Neapel. 1888;8:385–440.

18. Ruder T, Sunagar K, Undheim EA, Ali SA, Wai TC, Low DH, et al. Molecular phylogeny and evolution of the proteins encoded by coleoid (cuttlefish, octopus, and squid) posterior venom glands. Journal of molecular evolution. 2013;76(4):192–204. doi: 10.1007/s00239-013-9552-5 23456102.

19. Ghiretti F. Toxicity of octopus saliva against crustacea. Annals of the New York Academy of Sciences. 1960;90:726–41. 13704937

20. Ghiretti F. Cephalotoxin: the crab-paralysing agent of the posterior salivary glands of cephalopods. Nature. 1959;183:1192–3.

21. Edgecombe GD, Giribet G. Evolutionary biology of centipedes (Myriapoda: Chilopoda). Annual review of entomology. 2007;52:151–70. doi: 10.1146/annurev.ento.52.110405.091326 16872257.

22. Balit CR, Harvey MS, Waldock JM, Isbister GK. Prospective study of centipede bites in Australia. Journal of toxicology Clinical toxicology. 2004;42(1):41–8. Epub 2004/04/16. 15083935.

23. Malta MB, Lira MS, Soares SL, Rocha GC, Knysak I, Martins R, et al. Toxic activities of Brazilian centipede venoms. Toxicon: official journal of the International Society on Toxinology. 2008;52(2):255–63. doi: 10.1016/j.toxicon.2008.05.012 18586047.

24. McKeown K. Centipedes and centipede bites. The Australian Museum Magazine. 1930;(4):59–60.

25. King GF, Hardy MC. Spider-venom peptides: structure, pharmacology, and potential for control of insect pests. Annual review of entomology. 2013;58:475–96. doi: 10.1146/annurev-ento-120811-153650 23020618.

26. Jouiaei M, Sunagar K, Federman Gross A, Scheib H, Alewood PF, Moran Y, et al. 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. 2015;32(6):1598–610. doi: 10.1093/molbev/msv050 25757852.

27. Undheim EA, Sunagar K, Hamilton BR, Jones A, Venter DJ, Fry BG, et al. Multifunctional warheads: diversification of the toxin arsenal of centipedes via novel multidomain transcripts. Journal of proteomics. 2014;102:1–10. doi: 10.1016/j.jprot.2014.02.024 24602922.

28. Undheim EA, Jones A, Clauser KR, Holland JW, Pineda SS, King GF, et al. Clawing through evolution: toxin diversification and convergence in the ancient lineage Chilopoda (centipedes). Molecular biology and evolution. 2014;31(8):2124–48. Epub 2014/05/23. doi: 10.1093/molbev/msu162 24847043; PubMed Central PMCID: PMCPmc4104317.

29. Anderson LI, Trewin NH. An Early Devonian arthropod fauna from the Windyfield cherts, Aberdeenshire, Scotland. Palaeontology. 2003;46:467–509. doi: 10.1111/1475-4983.00308 WOS:000183159900003.

30. Ozbek S, Balasubramanian PG, Holstein TW. Cnidocyst structure and the biomechanics of discharge. Toxicon: official journal of the International Society on Toxinology. 2009;54(8):1038–45. doi: 10.1016/j.toxicon.2009.03.006 19286000.

31. Kuhn-Nentwig L, Stocklin R, Nentwig W. Venom composition and strategies in spiders: Is everything possible? In Advances in Insect Physiology. Spider Physiology and Behaviour, ed. Casas J. Burlington, MA: Academic. 2011:1–86.

32. Gess RW. The earliest record of terrestrial animals in Gondwana: A scorpion from the Famennian (Late Devonian) Witpoort Formation of South Africa. African Invertebrates. 2013;54(2):373–9.

33. Foelix R, Erb B. Mesothelae have venom glands. Journal of Arachnology. 2010;38(3):596–8. doi: 10.1636/B10-30.1

34. Fry BG, Vidal N, Norman JA, Vonk FJ, Scheib H, Ramjan SF, et al. Early evolution of the venom system in lizards and snakes. Nature. 2006;439(7076):584–8. doi: 10.1038/nature04328 16292255.

35. Fry BG, Roelants K, Norman JA. Tentacles of venom: toxic protein convergence in the Kingdom Animalia. Journal of molecular evolution. 2009;68(4):311–21. doi: 10.1007/s00239-009-9223-8 19294452.

36. Olivera BM, Showers Corneli P, Watkins M, Fedosov A. Biodiversity of Cone Snails and Other Venomous Marine Gastropods: Evolutionary Success Through Neuropharmacology. Annual Review of Animal Biosciences. 2014;2(1):487–513. doi: 10.1146/annurev-animal-022513-114124 25384153.

37. Undheim EA, Sunagar K, Herzig V, Kely L, Low DH, Jackson TN, et al. A proteomics and transcriptomics investigation of the venom from the barychelid spider Trittame loki (brush-foot trapdoor). Toxins. 2013;5(12):2488–503. doi: 10.3390/toxins5122488 24351713; PubMed Central PMCID: PMC3873697.

38. Pineda SS, Sollod BL, Wilson D, Darling A, Sunagar K, Undheim EA, et al. Diversification of a single ancestral gene into a successful toxin superfamily in highly venomous Australian funnel-web spiders. BMC genomics. 2014;15:177. doi: 10.1186/1471-2164-15-177 24593665; PubMed Central PMCID: PMC4029134.

39. Binford GJ, Bodner MR, Cordes MH, Baldwin KL, Rynerson MR, Burns SN, et al. Molecular evolution, functional variation, and proposed nomenclature of the gene family that includes sphingomyelinase D in sicariid spider venoms. Molecular biology and evolution. 2009;26(3):547–66. doi: 10.1093/molbev/msn274 19042943; PubMed Central PMCID: PMC2767091.

40. Garb JE, Hayashi CY. Molecular evolution of alpha-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom. Molecular biology and evolution. 2013;30(5):999–1014. doi: 10.1093/molbev/mst011 23339183; PubMed Central PMCID: PMC3670729.

41. Undheim EA, King GF. On the venom system of centipedes (Chilopoda), a neglected group of venomous animals. Toxicon: official journal of the International Society on Toxinology. 2011;57(4):512–24. Epub 2011/01/25. doi: 10.1016/j.toxicon.2011.01.004 21255597.

42. Liu ZC, Zhang R, Zhao F, Chen ZM, Liu HW, Wang YJ, et al. Venomic and transcriptomic analysis of centipede Scolopendra subspinipes dehaani. Journal of proteome research. 2012;11(12):6197–212. doi: 10.1021/pr300881d 23148443.

43. Yang S, Liu Z, Xiao Y, Li Y, Rong M, Liang S, et al. Chemical punch packed in venoms makes centipedes excellent predators. Molecular & cellular proteomics: MCP. 2012;11(9):640–50. doi: 10.1074/mcp.M112.018853 22595790; PubMed Central PMCID: PMC3434766.

44. Selden PA, Shear WA, Bonamo PM. A spider and other arachnids from the Devonian of New York, and reinterpretations of Devonian Araneae. Palaeontology. 1991;34:241–81.

45. Ayoub NA, Hayashi CY. Spiders (Araneae) in The Timetree of Life, Hedges S. B. and Kumar S., Eds. Oxford University Press. 2009:255–9.

46. Penney D. Spider Research in the 21st Century: Trends and Perspectives: Siri Scientific Press; 2013.

47. Zhang Y, Chen J, Tang X, Wang F, Jiang L, Xiong X, et al. Transcriptome analysis of the venom glands of the Chinese wolf spider Lycosa singoriensis. Zoology. 2010;113(1):10–8. doi: 10.1016/j.zool.2009.04.001 19875276.

48. Chen J, Deng M, He Q, Meng E, Jiang L, Liao Z, et al. Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao. Cellular and molecular life sciences: CMLS. 2008;65(15):2431–44. Epub 2008/06/27. doi: 10.1007/s00018-008-8135-x 18581053.

49. Kiyatkin NI, Dulubova IE, Chekhovskaya IA, Grishin EV. Cloning and structure of cDNA encoding alpha-latrotoxin from black widow spider venom. FEBS Lett. 1990;270(1–2):127–31. 1977615.

50. Ushkaryov YA, Rohou A, Sugita S. alpha-Latrotoxin and its receptors. Handb Exp Pharmacol. 2008;(184):171–206. Epub 2007/12/08. doi: 10.1007/978-3-540-74805-2_7 18064415; PubMed Central PMCID: PMCPMC2519134.

51. Swanson DL, Vetter RS. Loxoscelism. Clin Dermatol. 2006;24(3):213–21. doi: 10.1016/j.clindermatol.2005.11.006 16714202.

52. Liang SP, Chen XD, Shu Q, Zhang Y, Peng K. The presynaptic activity of huwentoxin-I, a neurotoxin from the venom of the chinese bird spider Selenocosmia huwena. Toxicon: official journal of the International Society on Toxinology. 2000;38(9):1237–46. Epub 2000/03/29. 10736477.

53. Herzig V, Wood DL, Newell F, Chaumeil PA, Kaas Q, Binford GJ, et al. ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures. Nucleic Acids Res. 2011;39(Database issue):D653–7. doi: 10.1093/nar/gkq1058 21036864; PubMed Central PMCID: PMC3013666.

54. Yuan CH, He QY, Peng K, Diao JB, Jiang LP, Tang X, et al. Discovery of a distinct superfamily of Kunitz-type toxin (KTT) from tarantulas. PloS one. 2008;3(10):e3414. Epub 2008/10/17. doi: 10.1371/journal.pone.0003414 18923708; PubMed Central PMCID: PMCPMC2561067.

55. Corzo G, Gilles N, Satake H, Villegas E, Dai L, Nakajima T, et al. Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel. FEBS Lett. 2003;547(1–3):43–50. Epub 2003/07/16. 12860384.

56. Bloomquist JR. Mode of action of atracotoxin at central and peripheral synapses of insects. Invert Neurosci. 2003;5(1):45–50. Epub 2003/11/11. doi: 10.1007/s10158-003-0027-z 14608494.

57. Gunning SJ, Maggio F, Windley MJ, Valenzuela SM, King GF, Nicholson GM. The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels. The FEBS journal. 2008;275(16):4045–59. Epub 2008/07/16. doi: 10.1111/j.1742-4658.2008.06545.x 18625007.

58. Sunagar K, Undheim EA, Chan AH, Koludarov I, Munoz-Gomez SA, Antunes A, et al. Evolution stings: the origin and diversification of scorpion toxin peptide scaffolds. Toxins. 2013;5(12):2456–87. doi: 10.3390/toxins5122456 24351712; PubMed Central PMCID: PMC3873696.

59. Sunagar K, Jackson TN, Undheim EA, Ali SA, Antunes A, Fry BG. Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins. Toxins. 2013;5(11):2172–208. doi: 10.3390/toxins5112172 24253238; PubMed Central PMCID: PMC3847720.

60. Brust A, Sunagar K, Undheim EA, Vetter I, Yang DC, Casewell NR, et al. Differential evolution and neofunctionalization of snake venom metalloprotease domains. Molecular & cellular proteomics: MCP. 2013;12(3):651–63. doi: 10.1074/mcp.M112.023135 23242553; PubMed Central PMCID: PMC3591658.

61. Juarez P, Comas I, Gonzalez-Candelas F, Calvete JJ. Evolution of snake venom disintegrins by positive Darwinian selection. Molecular biology and evolution. 2008;25(11):2391–407. Epub 2008/08/15. doi: 10.1093/molbev/msn179 18701431.

62. Sunagar K, Undheim EA, Scheib H, Gren EC, Cochran C, Person CE, et al. Intraspecific venom variation in the medically significant Southern Pacific Rattlesnake (Crotalus oreganus helleri): biodiscovery, clinical and evolutionary implications. J Proteomics. 2014;99:68–83. doi: 10.1016/j.jprot.2014.01.013 24463169.

63. Hedges SB, Vidal N. Lizards, snakes, and amphisbaenians (Squamata) in The Timetree of Life, Hedges S. B. and Kumar S., Eds. Oxford University Press. 2009:383–9.

64. Casewell NR, Wuster W, Vonk FJ, Harrison RA, Fry BG. Complex cocktails: the evolutionary novelty of venoms. Trends in ecology & evolution. 2013;28(4):219–29. doi: 10.1016/j.tree.2012.10.020 23219381.

65. Van Valen L. A new evolutionary law. Evolutionary Theory. 1973;1:1–30.

66. Rachamim T, Morgenstern D, Aharonovich D, Brekhman V, Lotan T, Sher D. The Dynamically Evolving Nematocyst Content of an Anthozoan, a Scyphozoan, and a Hydrozoan. Molecular biology and evolution. 2014. doi: 10.1093/molbev/msu335 25518955.

67. Kristan K, Podlesek Z, Hojnik V, Gutierrez-Aguirre I, Guncar G, Turk D, et al. Pore formation by equinatoxin, a eukaryotic pore-forming toxin, requires a flexible N-terminal region and a stable beta-sandwich. The Journal of biological chemistry. 2004;279(45):46509–17. doi: 10.1074/jbc.M406193200 15322132.

68. Kumar TK, Jayaraman G, Lee CS, Arunkumar AI, Sivaraman T, Samuel D, et al. Snake venom cardiotoxins-structure, dynamics, function and folding. Journal of biomolecular structure & dynamics. 1997;15(3):431–63. Epub 1998/01/24. doi: 10.1080/07391102.1997.10508957 9439993.

69. Nascimento FD, Hayashi MA, Kerkis A, Oliveira V, Oliveira EB, Radis-Baptista G, et al. Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans. The Journal of biological chemistry. 2007;282(29):21349–60. Epub 2007/05/11. doi: 10.1074/jbc.M604876200 17491023.

70. Chipman AD, Ferrier DE, Brena C, Qu J, Hughes DS, Schroder R, et al. The First Myriapod Genome Sequence Reveals Conservative Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima. PLoS Biol. 2014;12(11):e1002005. doi: 10.1371/journal.pbio.1002005 25423365; PubMed Central PMCID: PMC4244043.

71. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. Journal of molecular biology. 1990;215(3):403–10. doi: 10.1016/S0022-2836(05)80360-2 2231712.

72. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic acids research. 2004;32(5):1792–7. doi: 10.1093/nar/gkh340 15034147; PubMed Central PMCID: PMC390337.

73. Darriba D, Taboada GL, Doallo R, Posada D. jModelTest 2: more models, new heuristics and parallel computing. Nat Methods. 2012;9(8):772. doi: 10.1038/nmeth.2109 22847109.

74. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Systematic biology. 2010;59(3):307–21. doi: 10.1093/sysbio/syq010 20525638.

75. Yang Z. Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Molecular biology and evolution. 1998;15(5):568–73. 9580986.

76. Yang Z. PAML 4: phylogenetic analysis by maximum likelihood. Molecular biology and evolution. 2007;24(8):1586–91. doi: 10.1093/molbev/msm088 17483113.

77. Nielsen R, Yang Z. Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics. 1998;148(3):929–36. 9539414; PubMed Central PMCID: PMCPMC1460041.

78. Yang Z, Wong WS, Nielsen R. Bayes empirical bayes inference of amino acid sites under positive selection. Molecular biology and evolution. 2005;22(4):1107–18. doi: 10.1093/molbev/msi097 15689528.

79. Pond SL, Frost SD, Muse SV. HyPhy: hypothesis testing using phylogenies. Bioinformatics. 2005;21(5):676–9. doi: 10.1093/bioinformatics/bti079 15509596.

80. Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL, et al. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Molecular biology and evolution. 2013;30(5):1196–205. doi: 10.1093/molbev/mst030 23420840; PubMed Central PMCID: PMC3670733.

81. Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Kosakovsky Pond SL. Detecting individual sites subject to episodic diversifying selection. PLoS genetics. 2012;8(7):e1002764. doi: 10.1371/journal.pgen.1002764 22807683; PubMed Central PMCID: PMC3395634.

82. Xia X, Xie Z, Salemi M, Chen L, Wang Y. An index of substitution saturation and its application. Molecular phylogenetics and evolution. 2003;26(1):1–7. 12470932.

83. Xia X, Lemey P. Assessing substitution saturation with DAMBE in Philippe Lemey, Marco Salemi and Anne-Mieke Vandamme, eds. The Phylogenetic Handbook: A Practical Approach to DNA and Protein Phylogeny. 2nd edition Cambridge University Press. 2009:615–30.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#