В статье обобщены литературные данные об особенностях механизмов спонтанного и индуцированного мутагенеза. Их изучение позволит расширить представления о роли мутаций в видообразовании и эволюции организмов, а также предвидеть интенсивность и характер мутационных изменений в природных популяциях на техногенно загрязненных территориях. Акцентируется внимание на признании трех разных подходов относительно природы возникновения спонтанных точечных мутаций: таутомерная гипотеза; ионизационный механизм; подход, оперирующий неправильными парами оснований ДНК в основной, канонической таутомерной форме как источником мутаций. Отмечается, что именно физико-химическое свойство неправильных пар оснований ДНК с Утсон-Криковской и вобл-архитектурами, связанное с контролированием высокостабильными переходными парами, является новым ключом к пониманию природы спонтанного точечного мутагенеза. Обсуждаются условия, обеспечивающие реализацию первичных повреждений ДНК в мутации. Среди них особая роль отводится эффективности репарационных процессов, которая оказывается разной при неодинаковых дозовых нагрузках мутагенов. Приведены доказательства возрастания частоты мутаций вследствие резких изменений условий окружающей среды, которые вызывают активирование некодирующих белки нуклеотидных последовательностей, мобильных генетических элементов разных классов и соответствующих малым РНК последовательностей. Описываются механизмы индуцированного мутагенеза в условиях влияния высоких и низких доз ионизирующего излучения и химических мутагенов. Показано, что индуцированные облучением с малой линейной передачей энергии немишенные эффекты связаны с образованием генотоксических соединений и ослаблением интенсивности процессов репарации ДНК. Химические мутагенные факторы индуцируют возрастание частоты и спектра нарушений молекулы ДНК, что обусловлено высоким сродством химических мутагенов со структурами генетического материала. Химические мутагены при низких и умеренных концентрациях способны индуцировать высокую частоту точечных мутаций и низкий уровень хромосомных перестроек; при высоких концентрациях — проявляют радиомиметические свойства. Дальнейшее познание механизмов спонтанного мутагенеза и генетического ответа биологической системы на внешние стрессы позволит осуществлять поиск новых мутагенных факторов, которые вызывали бы высокий уровень управляемой селекционером изменчивости организмов, и определять пути избежания их негативных генетических последствий в случае попадания в окружающую среду.
Ключевые слова: механизмы мутагенеза, спонтанные и индуцированные мутации, системы репарации, первичные повреждения ДНК, немишенные эффекты
Полный текст и дополнительные материалы
В свободном доступе: PDFЦитированная литература
1. Abilev, S.K. (2012). Chemical mutagens and genetic toxicology. Priroda, No. 10, pp. 39-46 [in Russian].
2. Abilev, S.K. & Glazer, V.M. (2015). Mutagenesis with the basics of genotoxicology. Moskva; Sankt-Peterburg: Nestor-Istoriya [in Russian].
3. Andreev, S.G., Eydelman, Yu., Hvostunov, I.K., Salnikov, I.V. & Talyizina, T.A. (2005). Biophysical modeling of radiation damage to the genetic structures of cells. Radiation biology. Radioecology, 45, No. 5, pp. 549-560 [in Russian].
4. Baranov, A.A. & Albitskiy, V.Yu. (2009). Mortality of the child population of Russia (trends, causes and ways to reduce). Moskva: Pediatr' [in Russian].
5. Bezrukova, M.V., Fathutdinova, R.A. & Shakirova, F.M. (2016). The protective effect of wheat germ agglutinin on mitosis in the roots of Triticum aestivum seedlings when exposed to cadmium. Fiziologiya rasteniy, 63, No. 3, pp. 382-389 [in Russian]. https://doi.org/10.1134/S102144371603002X
6. Belko, N.B., Gordey, I.A., Schetko, I.S. & Gordey, I.S. (2011). The creation of tetraploid forms of winter rye (Secale cereal L.) using nitrous oxide and the genetic effects of genome duplication. Faktory eksperymentalnoi evoliutsii orhanizmiv, No. 10, pp. 15-20 [in Russian].
7. Brovarets, O.O. & Hovorun, D.M. (2014). Molecular logic of spontaneous point mutagenesis: variation on the theme... Ukrainica Bioorganica Acta, No. 1, pp. 48-55 [in Ukrainian].
8. Burlakova, E.B., Konradov, A.A. & Maltseva, E.L. (2003). Effect of ultra-small doses of biologically active substances and low-intensity physical factors. Fizicheskaya himiya, 22, No. 2, pp. 4-15 [in Russian].
9. Vergolyas, M.R., Lutsenko, T.V. & Goncharuk, V.V. (2013). Cytotoxic effect of chlorphenols on cells of the root meristem of the seeds of onion (Allium fistulosum L.). Cytology and Genetics, 47, No. 1, pp. 44-49 [in Ukrainian]. https://doi.org/10.3103/S0095452713010118
10. Guskov, E.P., Mashkina, E.V., Belichenko, N.I., Varduni, T.V., Volosovtsova, G.I., Pokudina, I.O., Guskov, G.E. & Shkurat, T.P. (2009). Mutation processes in animals pre-adapted to oxidative stress. Ekologicheskaya genetika, 7, No. 1, pp. 41-48 [in Russian].
11. Davydenko, V.M. (2011). Radiobiology. Mykolaiv: MDAU [in Ukrainian].
12. Ezheva, T.A. & Shirokova, A.V. (2012). New possibilities of chemical mutagenesis. Priroda, No. 10, pp. 32-38 [in Russian].
13. Efimova, N.V., Rukavishnikov, V.S. & Zarodnyuk, T.S. (2007). Development of measures to maintain health in the programs of socio-economic development of the Russian Federation. Gigiena i sanitariya, No. 5, pp. 72-74 [in Russian].
14. Zaychenko, E.Yu., Severinovskaya, E.V., Dvoretskiy, A.I. & Marenkov, O.N. (2014). Ecological hazard of radiation-chemical pollution of the Dnieper region. Ekolohiia i pryrodokorystuvannia, No. 18, pp. 84-94 [in Russian].
15. Inge-Vechtomov, S.G. (2010). Genetics with the basics of selection. Sankt-Peterburg: OOO "IzdatelstvoN-L" [in Russian].
16. Karpova, I.S. (2016). Discovery of mutagenic action of DNA in the light of lateral genomics. Faktory eksperymentalnoi evoliutsii orhanizmiv, No. 19, pp. 247-251 [in Russian].
17. Kunakh, V.A. (2013). Mobile genetic elements and plasticity of the plant genome. Kyiv: Lohos [in Ukrainian].
18. Litvyakov, N.V., Freydin, M.B., Halyuzova, M.V., Cazonov, A., Vasileva, E.O., Albah, E.N., Isubakova, D.S., Blinov, A.P., Rodionova, V.I., Kutko, A.A., Karpov, A.B. & Tahauov, R.M. (2014). The frequency and spectrum of cytogenetic disorders in workers of the Siberian Chemical Combine. Radiation biology. Radioecology, 54, No. 3. pp. 283-296 [in Russian]. https://doi.org/10.7868/S0869803113020069
19. Lobashev, M.E. (1947). Physiological (paranecrotic) hypothesis of the mutation process. Vestnik Leningradskogo gosudarstvennogo universiteta, No. 8, pp. 10-29 [in Russian].
20. Mihaylov, V.F., Mazurik, V.K., Burlakova, E.B., Ushenkova, L.N. & Raeva, N.F. (2005). Molecular manifestations of radiation-induced genomic instability: the possibility of chemical modification.Radiation biology. Radioecology, 45, No. 5, pp. 561-570 [in Russian].
21. Morgun, V.V. & Larchenko, K.A. (2006). Genetic effects of exogenous DNA when interacting with the genome of higher plants. Fiziologiya i biohimiya kulturnyih rasteniy, 38, No. 2, pp. 102-109 [in Ukrainian].
22. Nasonov, D.N. & Aleksandrov, V. Ya. (1940). The reaction of living matter to external influences. The denaturation theory of damage and irritation. Moskva: Akademiya nauk SSSR [in Russian].
23. Patrushev, L.I. & Minkevich, I.G. (2006). Non-coding sequences of the eukaryotic genome create an additional level of gene protection against chemical mutagens. Bioorganicheskaya himiya, 32, No. 4, pp. 408-413 [in Russian]. https://doi.org/10.1134/S1068162006040078
24. Serkiz, Ya.I. (1995). Long-term effects, incidence and life expectancy. Chernobyl disaster. Kyiv: Naukova dumka [in Russian].
25. Stroeva, O.G. (2012). The mechanism of chemical mutagenesis in the light of the microgenetic concept I.A. Rapoport. Induced mutagenesis in plant breeding (pp. 6-12), Bila Tserkva [in Ukrainian].
26. Syicheva, L.P. (2007). Biological significance, determination criteria and limits of variation of the full range of karyological parameters in assessing the cytogenetic status of a person. Meditsinskaya genetika, 6, No. 11, pp. 3-11 [in Russian].
27. Syicheva, L.P., Zhurkov, V.S. & Rahmanin, Yu.A. (2013). Actual problems of genetic toxicology. Genetics, 49, No. 3, pp. 293-302 [in Russian]. https://doi.org/10.1134/S1022795413030162
28. Timofeev-Ressovsky, N.V. (2009). Selected works. Moskva: Nauka [in Russian].
29. Ulyanenko, S.E., Potetnya, V.I., Koryakin, S.N., Lyichagin, A.A., Koryakina, E.V., Solovev, A.N., Beketov, E.E. & Isaeva, E.V. (2016, November).Settlement and experimental modeling of radiobiological effects at the molecular genetic level when exposed to radiation of different quality.International Scientific Conference Actual problems of radiobiology and astrobiology. Genetic and epigenetic effects of ionizing radiation (pp. 65-67), Dubna [in Russian].
30. Hesin, R.B. (1984). Genome Inconsistency. Moskva: Nauka [in Russian].
31. Chernenkov, A.Yu., Fedorov, D.V., Kosareva, A.A., Kozhina, T.N. & Korolev, V.G. (2014). Change in the frequencies of spontaneous mutagenesis with combinations of the hsm3 and hsm6 mutations with the rad52 mutation in Saccharomyces cerevisiae yeast cells. Genetics, 50, No. 2, pp. 243-245 [in Russian]. https://doi.org/10.1134/S1022795414020057
32. Shevchenko, V.A. & Snigireva, G.P. (2006). Significance of cytogenetic examination to assess the consequences of the Chernobyl disaster. Radiation biology. Radioecology, 46, No. 2, pp. 133-139 [in Russian].
33. Eyges, N.S. (2013). The historical role of Joseph Abramovich Rapoport in genetics. Continuation of research using the method of chemical mutagenesis. Vavilovskiy zhurnal genetiki I selektsii, 17, No. 1, pp. 162-172 [in Russian].
34. Eygest, N.S., Volchenko, G.A., Vaysfeld, L.I. & Volchenko, S.G. (2011). Adaptive properties of winter wheat obtained by methods of hereditary and non-hereditary variability. Sovremennyiy mir, priroda i chelovek, 2, No. 1, pp. 55-58 [in Russian].
35. Yakymchuk, R.A. (2019). Long-term genetic effects of radiation on organisms. The Bulletin of Kharkiv national agrarian university. Series Biology, 47, No. 2, pp. 6-22 [in Ukrainian].
36. Yakymchuk, R.A. & Morhun, V.V. (2015). Cytogenetic evaluation of the spontaneous level of winter wheat mutations in different ecological and geographical regions of Ukraine. Fiziol. rast. genet., 47, No. 2, pp. 126-135 [in Ukrainian].
37. Basu, S., Je, G. & Kim, Y. S. (2015). Transcriptional mutagenesis by 8-oxodG in alpha-synuclein aggregation and the pathogenesis of Parkinson's disease. Experimental & Molecular Medicine, 47, p. 179. https://doi.org/10.1038/emm.2015.54
38. Bernstein, C., Prasad, A.R. & Nfonsam, V. (2013). DNA damage, DNA repair and cancer. New Research Directions in DNA Repair. Publisher: InTech. https://doi.org/10.5772/53919
39. Boiteux, S. & Guillet, M. (2004). Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae. DNA Repair, 3, No. 1, pp. 1-12. https://doi.org/10.1016/j.dnarep.2003.10.002
40. Breysse, P.N. (Ed.) (2005). Toxicological profile for lead. Agency for toxic substances and disease registry division of toxicology and environmental medicine. Atlanta.
41. Bulathsinghala, A.T. & Shaw, I.C. (2013). The toxic chemistry of methyl bromide. Human & Experimental Toxicology, 33, No. 1, pp. 81-91. https://doi.org/10.1177/0960327113493299
42. Chernenkov, A., Fedorov, D., Kosareva, A., Kozhina, T., Evstiukhina, T., Peshekhonov, V. & Korolev, V. (2013). The role of Saccharomyces cerevisiae HSM3 and HSM6 genes in DNA repair, mutagenesis and chromatin modifications. The FEBS Journal, 280, No. 1, p. 65.
43. Dexheimer, T.S. (2013). DNA repair pathways and mechanisms. DNA Repair of Cancer Stem Cells, Springer Netherlands. https://doi.org/10.1007/978-94-007-4590-2_2
44. Donbak, L., Celik, M., Demirhan, I. & Nagas, S. (2007). Genotoxic damage in Maras powder consumers from kahramanmaras province of Turkey. Genetics, 43, No. 5, pp. 636-637. https://doi.org/10.1134/S1022795407050055
45. Fonseca Guerra, C., Bickelhaupt, F.M., Saha, S. & Wang, F. (2006). Adenine tautomers: relative stabilities, ionization energies, and mismatch with cytosine. The Journal of Physical Chemistry, 110, No. 11, pp. 4012-4020. https://doi.org/10.1021/jp057275r
46. Furmanchuk, A., Isayev, O., Gorb, L., Shishkin, O.V., Hovorun, D.M. & Leszczynski, J. (2011). Novel view on the mechanism of water-assisted proton transfer in the DNA bases: Bulk water hydration. Physical Chemistry Chemical Physics, 13, No. 10, pp. 4311-4317. https://doi.org/10.1039/c0cp02177f
47. Keeling, P.J. & Palmer, J.D. (2008). Horizontal gene transfer in eukaryotic evolution. Nature Reviews Genetics, 9, pp. 605-618. https://doi.org/10.1038/nrg2386
48. Kennard, O. (1985). Structural studies of DNA fragments: the G·T wobble base pair in A, B and Z DNA; the G·A base pair in BDNA. Journal of Biomolecular Structure and Dynamics, 3, No. 2, pp. 205-225. https://doi.org/10.1080/07391102.1985.10508412
49. Lindahl, T. & Andersson, A. (1972). Rate of chain breakage at apurinic sites in double-stranded deoxyribonucleic acid. Biochemistry, 11, No. 19, pp. 3618-3623. https://doi.org/10.1021/bi00769a019
50. Lynch, M. (2016). Mutation and humanexceptionalism: our future genetic load. Genetics, 202, pp. 869-875. https://doi.org/10.1534/genetics.115.180471
51. Morgun, V.V. & Yakymchuk, R.A. (2018). Cytogenetic anomalies of winter wheat cells, induced by chemical contamination of the territory of Kalush industrial district. Regulatory Mechanisms in Biosystems, 9, No. 3, pp. 446-452. https://doi.org/10.15421/021867
52. Natarajan, A.T., Berni, A., Marimuthu, K.M. & Palitti, F. (2008). The type and yield of ionizing radiation induced chromosomal aberrations depend on the efficiency of different DSB repair pathways in mammalian cells. Mutation Research, 642, pp. 80-85. https://doi.org/10.1016/j.mrfmmm.2008.05.002
53. Nelson, H.H., Marsit, C.J. & Kelsey, K.T. (2011). Global methylation in exposure biology and translational medical science. Environmental Health Perspectives, 119, No. 11, pp. 1528-1533. https://doi.org/10.1289/ehp.1103423
54. Oladosu, Y., Rafii, M.Y., Abdullah, N., Hussind, G., Ramlie, A., Rahim, H. A., Miaha, G. & Usmana, M. (2016). Principle and application of plant mutagenesis in crop improvement: a review. Biotechnology & Biotechnological Equipment, 30, No. 1, pp. 1-16. https://doi.org/10.1080/13102818.2015.1087333
55. Pierce, B.A. (2012). Genetics: A conceptual approach fourth edition. New York: W.H. Freeman.
56. Rodin, S.N. & Riggs, A.D. (2003). Epigenetic silencing may and evolution by gene duplication. Journal of Molecular Evolution, 56, pp. 718-729. https://doi.org/10.1007/s00239-002-2446-6
57. Topal, M.D. & Fresco, J.R. (1976). Complementary base pairing and the origin of substitution mutations. Nature, 263, No. 5575, pp. 285-289. https://doi.org/10.1038/263285a0
58. Venken, K.J.T., & Bellen, H.J. (2014). Chemical mutagens, transposons, and transgenes to interrogate gene function in Drosophila melanogaster. Methods, 68, No. 1, pp. 15-28. https://doi.org/10.1016/j.ymeth.2014.02.025
59. Yakymchuk, R.A. (2018). Cytogenetic activity of radionuclide contamination of water reservoirs of the alienation zone of Chornobyl NPP. Regulatory Mechanisms in Biosystems, 9, No. 2, pp. 189-197. https://doi.org/10.15421/021828
60. Yakymchuk, R.A. (2015). Cytogenetic after-effects of mutagen soil contamination with emissions of Burshtynska thermal power station. In Opalko, A. I. (ed.). Ecological consequences of increasing crop productivity. Plant breeding and biotic diversity (pp. 217-227), Toronto; New Jersey: Apple Academic Press. https://doi.org/10.1201/b17477-25
61. Yakymchuk, R.A. (2018). Cytogenetic disorders in Triticum aestivum L. cells affected by radionuclide contamination of water reservoirs in the alienation zone of Chornobyl NPP. Biopolymers and Cell, 34, No. 2, pp. 97-106. https://doi.org/10.7124/bc.000974