Молекулярная биология, 2021, T. 55, № 6, стр. 927-943

Полногеномные дупликации в эволюции, онтогенезе и патологии: резерв сложности и запаса прочности

О. В. Анацкая a*, А. Е. Виноградов a

a Институт цитологии Российской академии наук
194064 Санкт-Петербург, Россия

* E-mail: olga.anatskaya@gmail.com

Поступила в редакцию 03.03.2021
После доработки 07.05.2021
Принята к публикации 13.05.2021

Аннотация

Полногеномные дупликации (ПГД), или полиплоидия – это удвоение геномов, которое увеличивает количество генетической информации в клетке. ПГД целых организмов встречаются во всех ветвях эукариот и являются движущей силой видообразования, усложнения и адаптаций. ПГД найдены в соматических клетках всех типов тканей, они могут быть результатом нормальных и измененных онтогенетических программ, регенерации, патологических состояний, старения, малигнизации и метастазирования. Несмотря на универсальность ПГД, их функциональное значение, общие свойства и причины повышенной адаптивности недостаточно ясны. Сопоставление полнотранскриптомных данных и сведений из разных областей молекулярной биологии, геномики и молекулярной медицины показало, что полиплоидия как организмов, так и соматических и раковых клеток ассоциирована с рядом общих признаков, которые позволяют понять, какие именно свойства ПГД приводят к возникновению адаптивного фенотипа. Адаптивность ПГД может быть связана с увеличением сложности регуляции сетей и систем передачи сигналов, устойчивости к стрессу, активацией древних эволюционных программ одноклеточности, путей морфогенеза, выживания и продления жизни. В результате стресса возможен сдвиг баланса между клеточным и организменным уровнями контроля регуляции работы генов в сторону приоритета выживания клетки, что может привести к сердечно-сосудистым заболеваниям и раку. Представленные сведения помогают понять, как полиплоидия создает новые фенотипы и почему она является движущей силой эволюции и важным регулятором биологических процессов в соматических клетках, онтогенезе, патогенезе, регенерации и канцерогенезе.

Ключевые слова: полиплоидия, эволюция, регенерация, канцерогенез, старение, сложность регуляции, устойчивость к стрессу

Список литературы

  1. Van de Peer Y., Mizrachi E., Marchal K. (2017) The evolutionary significance of polyploidy. Nat. Rev. Genet. 18, 411–424.

  2. Fox D.T., Soltis D.E., Soltis P.S., Ashman T.L., Van de Peer Y. (2020) Polyploidy: a biological force from cells to ecosystems. Trends Cell Biol. 30, 688–694.

  3. Ohno S. (1970) Evolution by Gene Duplication. Berlin, Heidelberg: Springer.

  4. Singh P.P., Isambert H. (2020) OHNOLOGS v2: a comprehensive resource for the genes retained from whole genome duplication in vertebrates. Nucl. Acids Res. 48, D724–730.

  5. Kreiner J.M., Kron P., Husband B.C. (2017) Frequency and maintenance of unreduced gametes in natural plant populations: associations with reproductive mode, life history and genome size. New Phytol. 214, 879–889.

  6. Clark J.W., Donoghue P.C.J. (2017) Constraining the timing of whole genome duplication in plant evolutionary history. Proc. Biol. Sci. 284, 20170912.

  7. Murat F., Armero A., Pont C., Klopp C., Salse J. (2017) Reconstructing the genome of the most recent common ancestor of flowering plants. Nat. Genet. 49, 490–496.

  8. Soppa J. (2017) Polyploidy and community structure. Nat. Microbiol. 2, 16261.

  9. Hu G., Wendel J.F. (2019) Cis-trans controls and regulatory novelty accompanying allopolyploidization. New Phytol. 221, 1691–1700.

  10. Rice A., Šmarda P., Novosolov M., Drori M., Glick L., Sabath N., Meiri S., Belmaker J., Mayrose I. (2019) The global biogeography of polyploid plants. Nat. Ecol. Evol. 3, 265–273.

  11. Yang L. Sado T., Hirt M.V., Pasco-Viel E., Arunachalam M., Li J.B., Wang X.Z., Freyhof J., Saitoh K., Simons A.M., Miya M., He S.P., Mayden R.L. (2015) Phylogeny and polyploidy: resolving the classification of cyprinine fishes (Teleostei: Cypriniformes). Mol. Phylogenet. Evol. 85, 97–116.

  12. Evans B.J., Carter T.F., Greenbaum E., Gvoždík V., Kelley D.B., McLaughlin P.J., Olivier Pauwels S.G., Portik D.M., Stanley E.L., Tinsley R.C., Tobias M.L., Blackburn D.C. (2015) Genetics, morphology, advertisement calls, and historical records distinguish six new polyploid species of african clawed frog (Xenopus, Pipidae) from West and Central Africa. PLoS One. 10, e0142823.

  13. Moritz C., Bi K. (2011) Spontaneous speciation by ploidy elevation: laboratory synthesis of a new clonal vertebrate. Proc. Natl. Acad. Sci. USA. 108, 9733–9734.

  14. Tiersch T.R., Beck M.L., Douglass M. (1991) ZZW autotriploidy in a blue-and-yellow macaw. Genetica. 84, 209–212.

  15. Evans B.J., Upham N.S., Golding G.B., Ojeda R.A., Ojeda A.A. (2017) Evolution of the largest mammalian genome. Genome Biol. Evol. 9, 1711–1724.

  16. Imai H., Fujii W., Kusakabe K.T., Kiso Y., Kano K. (2016) Effects of whole genome duplication on cell size and gene expression in mouse embryonic stem cells. J. Reprod. Dev. 62, 571–576.

  17. Otto S.P., Whitton J. (2000) Polyploid incidence and evolution. Annu. Rev. Genet. 34, 401–437.

  18. Ganem N.J., Pellman D. (2007) Limiting the proliferation of polyploid cells. Cell. 131, 437–440.

  19. Otto S.P. (2007) The evolutionary consequences of polyploidy. Cell. 131, 452–462.

  20. Cutie S., Huang G.N. (2021) Vertebrate cardiac regeneration: evolutionary and developmental perspectives. Cell Regen. 10, 6.

  21. Reyes A.A., Marcum R.D., He Y. (2021) Structure and function of chromatin remodelers. J. Mol. Biol. 433, 166929.

  22. Zhou L., Gui J. (2017) Natural and artificial polyploids in aquaculture. Aquaculture and Fisheries. 2, 103–111.

  23. Glombik M., Bačovský V., Hobza R., Kopecký D. (2020) Competition of parental genomes in plant hybrids. Front. Plant. Sci. 11, 200.

  24. Comai L. (2005) The advantages and disadvantages of being polyploid. Nat. Rev. Genet. 6, 836–846.

  25. Anatskaya O.V., Vinogradov A.E., Kudryavtsev B.N. (1994) Hepatocyte polyploidy and metabolism/life-history traits: hypotheses testing. J. Theor. Biol. 168, 191–199.

  26. Gemble S., Basto R. (2020) CHRONOCRISIS: when cell cycle asynchrony generates DNA damage in polyploid cells. Bioessays. 42, e2000105.

  27. Øvrebø J.I., Edgar B.A. (2018) Polyploidy in tissue homeostasis and regeneration. Development. 145, dev156034.

  28. Brukman N.G., Uygur B., Podbilewicz B., Chernomordik L.V. (2019) How cells fuse. J. Cell Biol. 218, 1436–1451.

  29. Gjelsvik K.J., Besen-McNally R., Losick V.P. (2019) Solving the polyploid mystery in health and disease. Trends Genet. 35, 6–14.

  30. Anatskaya O.V., Vinogradov A.E. (2007) Genome multiplication as adaptation to tissue survival: evidence from gene expression in mammalian heart and liver. Genomics. 89, 70–80.

  31. Schoenfelder K.P., Fox D.T. (2015) The expanding implications of polyploidy. J. Cell Biol. 209, 485–491.

  32. Varetti G., Pellman D. (2012) “Two” much of a good thing: telomere damage-induced genome doubling drives tumorigenesis. Cancer Cell. 21, 712–714.

  33. Priestley P., Baber J., Lolkema M.P., Steeghs N., de Bruijn E., Shale C., Duyvesteyn K., Haidari S., van Hoeck A., Onstenk W., Roepman P., Voda M., Bloemendal H.J., Tjan-Heijnen V.C.G., van Herpen C.M.L., Labots M., Witteveen P.O., Smit E.F., Sleijfer S., Voest E.E., Cuppen E. (2019) Pan-cancer whole-genome analyses of metastatic solid tumours. Nature. 575, 210–216.

  34. White-Gilbertson S., Voelkel-Johnson C. (2020) Giants and monsters: unexpected characters in the story of cancer recurrence. Adv. Cancer Res. 148, 201–232.

  35. Salmina K., Bojko A., Inashkina I., Staniak K., Dudkowska M., Podlesniy P., Rumnieks F., Vainshelbaum N.M., Pjanova D., Sikora E., Erenpreisa J. (2020) “Mitotic slippage” and extranuclear DNA in cancer chemoresistance: a focus on telomeres. Int. J. Mol. Sci. 21, 2779.

  36. Salmina K., Jankevics E., Huna A., Perminov D., Radovica I, Klymenko T., Ivanov A., Jascenko E., Scherthan H., Cragg M., Erenpreisa J. (2010) Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells. Exp. Cell Res. 316, 2099–2112.

  37. Erenpreisa J., Kalejs M., Cragg M.S. (2005) Mitotic catastrophe and endomitosis in tumour cells: an evolutionary key to a molecular solution. Cell Biol. Int. 29, 1012–1018.

  38. Walen K.H. (2012) Genome reversion process of endopolyploidy confers chromosome instability on the descendent diploid cells. Cell Biol. Int. 36, 137–145.

  39. Walen K.H. (2021) Cell cycle stress in normal human cells: a route to “first cells” (with/without fitness gain) and cancer-like cell-shape changes. Semin. Cancer Biol. https://doi.org/10.1016/j.semcancer.2020.12.023

  40. Cho Y., Kim Y.K. (2020) Cancer stem cells as a potential target to overcome multidrug resistance. Front Oncol. 10, 764.

  41. Liu J. (2018) The dualistic origin of human tumors. Semin. Cancer Biol. 53, 1–16.

  42. Erenpreisa J., Salmina K., Anatskaya O., Cragg M.S. (2020) Paradoxes of cancer: survival at the brink. Semin Cancer Biol. S1044-579X(20)30269-8. https://doi.org/10.1016/j.semcancer.2020.12.009

  43. Du K., Klopp C., Woltering J.M., Adolfi M.C., Feron R., Prokopov D., Makunin A., Kichigin I., Schmidt C., Fischer P., Kuhl H., Wuertz S., Gessner J., Kloas W., Cabau C., Iampietro C., Parrinello H., Tomlinson C., Journot L., Postlethwait J.H., Braasch I., Trifonov V., Warren W.C., Meyer A., Guiguen Y., Schartl M. (2020) The sterlet sturgeon genome sequence and the mechanisms of segmental rediploidization. Nat. Ecol. Evol. 4, 841–852.

  44. Robertson F.M., Gundappa M.K., Grammes F., Hvidsten T.R., Redmond A.K., Lien S., Martin S.A.M., Holland P.W.H., Sandve S.R., Macqueen D.J. (2017) Lineage-specific rediploidization is a mechanism to explain time-lags between genome duplication and evolutionary diversification. Genome Biol. 18, 111.

  45. Venkatachalam A.B., Parmar M.B., Wright J.M. (2017) Evolution of the duplicated intracellular lipid-binding protein genes of teleost fishes. Mol. Genet. Genomics. 292, 699–727.

  46. Cheng F., Wu J., Cai X., Liang J., Freeling M., Wang X. (2018) Gene retention, fractionation and subgenome differences in polyploid plants. Nat. Plants. 4, 258–268.

  47. Lynch M., Force A. (2000) The probability of duplicate gene preservation by subfunctionalization. Genetics. 154, 459–473.

  48. Conant G.C., Wolfe K.H. (2008) Turning a hobby into a job: how duplicated genes find new functions. Nat. Rev. Genet. 9, 938–950.

  49. Vinogradov A.E. (2009) Global versus local centrality in evolution of yeast protein network. J. Mol. Evol. 68, 192–196.

  50. Vinogradov A.E., Anatskaya O.V. (2009) Loss of protein interactions and regulatory divergence in yeast whole-genome duplicates. Genomics. 93, 534–542.

  51. Lucchetta E.M., Ohlstein B. (2017) Amitosis of polyploid cells regenerates functional stem cells in the Drosophila intestine. Cell Stem Cell. 20, 609–620.e6.

  52. Zybina T.G., Zybina E.V. (2020) Role of cell cycling and polyploidy in placental trophoblast of different mammalian species. Reprod. Domest. Anim. 55, 895–904.

  53. Ahmadbeigi N., Soleimani M., Vasei M., Gheisari Y., Mortazavi Y., Azadmanesh K., Omidkhoda A., Janzamin E., Nardi N.B. (2013) Isolation, characterization, and transplantation of bone marrow-derived cell components with hematopoietic stem cell niche properties. Stem Cells Dev. 22, 3052–3061.

  54. Erenpreisa J., Cragg M.S. (2010) MOS, aneuploidy and the ploidy cycle of cancer cells. Oncogene. 29, 5447–5451.

  55. Niu N., Mercado-Uribe I., Liu J. (2017) Dedifferentiation into blastomere-like cancer stem cells via formation of polyploid giant cancer cells. Oncogene. 36, 4887–4900.

  56. Niculescu V.F. (2019) The reproductive life cycle of cancer: hypotheses of cell of origin, TP53 drivers and stem cell conversions in the light of the atavistic cancer cell theory. Med. Hypotheses. 123, 19–23.

  57. Liu J. (2020) The “life code”: A theory that unifies the human life cycle and the origin of human tumors. Semin. Cancer Biol. 60, 380–397.

  58. Niculescu V.F. (2020) aCLS cancers: genomic and epigenetic changes transform the cell of origin of cancer into a tumorigenic pathogen of unicellular organization and lifestyle. Gene. 726, 144174.

  59. Corrochano L.M., Kuo A., Marcet-Houben M., Polaino S., Salamov A., Villalobos-Escobedo J.M., Grimwood J., Álvarez M.I., Avalos J., Bauer D., Benito E.P., Benoit I., Burger G., Camino L.P., Cánovas D., Cerdá-Olmedo E., Cheng J.F., Domínguez A., Eliáš M., Eslava A.P., Glaser F., Gutiérrez G., Heitman J., Henrissat B., Iturriaga E.A., Lang B.F., Lavín J.L., Lee S.C., Li W., Lindquist E., López-García S., Luque E.M., Marcos A.T., Martin J., McCluskey K., Medina H.R., Miralles-Durán A., Miyazaki A., Muñoz-Torres E., Oguiza J.A., Ohm R.A., Olmedo M., Orejas M., Ortiz-Castellanos L., Pisabarro A.G., Rodríguez-Romero J., Ruiz-Herrera J., Ruiz-Vázquez R., Sanz C., Schackwitz W., Shahriari M., Shelest E., Silva-Franco F., Soanes D., Syed K., Tagua V.G., Talbot N.J., Thon M.R., Tice H., de Vries R.P., Wiebenga A., Yadav J.S., Braun E.L., Baker S.E., Garre V., Schmutz J., Horwitz B.A., Torres-Martínez S., Idnurm A., Herrera-Estrella A., Gabaldón T., Grigoriev I.V. (2016) Expansion of signal transduction pathways in fungi by extensive genome duplication. Curr. Biol. 26, 1577–1584.

  60. Vinogradov A.E., Anatskaya O.V. (2019) Evolutionary framework of the human interactome: unicellular and multicellular giant clusters. Biosystems. 181, 82–87.

  61. Mattenberger F., Sabater-Muñoz B., Toft C., Fares M.A. (2017) The phenotypic plasticity of duplicated genes in Saccharomyces cerevisiae and the origin of adaptations. G3 (Bethesda). 7, 63–75.

  62. Zhang K., Wang X., Cheng F. (2019) Plant polyploidy: origin, evolution, and its influence on crop domestication. Horticult. Plant J. 5, 231–239.

  63. Katsuda T., Hosaka K., Matsuzaki J., Usuba W., Prieto-Vila M., Yamaguchi T., Tsuchiya A., Terai S., Ochiya T. (2020) Transcriptomic dissection of hepatocyte heterogeneity: linking ploidy, zonation, and stem/progenitor cell characteristics. Cell. Mol. Gastroenterol. Hepatol. 9, 161–183.

  64. Broughton K.M., Khieu T., Nguyen N., Rosa M., Mohsin S., Quijada P., Wang B.J., Echeagaray O.H., Kubli D.A., Kim T., Firouzi F., Monsanto M.M., Gude N.A., Adamson R.M., Dembitsky W.P., Da-vis M.E., Sussman M.A. (2019) Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals. Commun. Biol. 2, 205.

  65. Fajka-Boja R., Marton A., Tóth A., Blazsó P., Tubak V., Bálint B., Nagy I., Hegedűs Z., Vizler C., Katona R.L. (2018) Increased insulin-like growth factor 1 production by polyploid adipose stem cells promotes growth of breast cancer cells. BMC Cancer. 18, 872.

  66. Anatskaya O.V., Vinogradov A.E., Vainshelbaum N.M., Giuliani A., Erenpreisa J. (2020) Phylostratic shift of whole-genome duplications in normal mammalian tissues towards unicellularity is driven by developmental bivalent genes and reveals a link to cancer. Int. J. Mol. Sci. 21, 8759.

  67. Vinogradov A.E., Anatskaya O.V. (2020) Cell-cycle dependence of transcriptome gene modules: comparison of regression lines. FEBS J. 287, 4427–4439.

  68. Moein S., Adibi R., da Silva Meirelles L., Nardi N.B., Gheisari Y. (2020) Cancer regeneration: polyploid cells are the key drivers of tumor progression. Biochim. Biophys. ActaRev. Cancer. 1874, 188408.

  69. Krigerts J., Salmina K., Freivalds T., Zayakin P., Rumnieks F., Inashkina I., Giuliani A., Hausmann M., Erenpreisa J. (2021) Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains. Biophys. J. 120, 711–724.

  70. Pienta K.J., Hammarlund E.U., Brown J.S., Amend S.R., Axelrod R.M. (2021) Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells. Proc. Natl. Acad. Sci. USA. 118, e2020838118.

  71. Neganova I., Zhang X., Atkinson S., Lako M. (2009) Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells. Oncogene. 28, 20–30.

  72. Neganova I., Vilella F., Atkinson S.P., Lloret M., Passos J.F., von Zglinicki T., O’Connor J.E., Burks D., Jones R., Armstrong L., Lako M. (2011) An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells. Stem Cells. 29, 651–659.

  73. Neganova I., Tilgner K., Buskin A., Paraskevopoulou I., Atkinson S.P., Peberdy D., Passos J.F., Lako M. (2014) CDK1 plays an important role in the maintenance of pluripotency and genomic stability in human pluripotent stem cells. Cell Death Dis. 5, e1508.

  74. Vinogradov A.E., Shilina M.A., Anatskaya O.V., Alekseenko L.L., Fridlyanskaya I.I., Krasnenko A., Kim A., Korostin D., Ilynsky V., Elmuratov A., Tsy-ganov O., Grinchuk T.M., Nikolsky NN. (2017) Molecular genetic analysis of human endometrial mesenchymal stem cells that survived sublethal heat shock. Stem Cells Int. 2017, 2362630.

  75. Shilina M.A., Grinchuk T.M., Anatskaya O.V., Vinogradov A.E., Alekseenko L.L., Elmuratov A.U., Nikolsky N.N. (2018) Cytogenetic and transcriptomic analysis of human endometrial MSC retaining proliferative activity after sublethal heat shock. Cells. 7, 184.

  76. Alekseenko L.L., Shilina M.A., Lyublinskaya O.G., Kornienko J.S., Anatskaya O.V., Vinogradov A.E., Grinchuk T.M., Fridlyanskaya I.I., Nikolsky N.N. (2018) Quiescent human mesenchymal stem cells are more resistant to heat stress than cycling cells. Stem Cells Int. 2018, 3753547.

  77. Vincent M.D. (2009) Optimizing the management of advanced non-small-cell lung cancer: a personal view. Curr. Oncol. 16, 9–21.

  78. Davies P.C.W., Lineweaver C.H. (2011) Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors. Phys. Biol. 8, 015001.

  79. Vinogradov A.E. (2010) Human transcriptome nexuses: basic-eukaryotic and metazoan. Genomics. 95, 345–354.

  80. Trigos A.S., Pearson R.B., Papenfuss A.T., Goode D.L. (2017) Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors. Proc. Natl. Acad. Sci. USA. 114, 6406–6411.

  81. Erenpreisa J., Salmina K., Huna A., Jackson T.R., Vazquez-Martin A., Cragg M.S. (2014) The “virgin birth”, polyploidy, and the origin of cancer. Oncoscience. 2, 3–14.

  82. Matsumoto T., Wakefield L., Peters A., Peto M., Spellman P., Grompe M. (2021) Proliferative polyploid cells give rise to tumors via ploidy reduction. Nat. Commun. 12, 646.

  83. Zhang S., Mercado-Uribe I., Xing Z., Sun B., Kuang J., Liu J. (2014) Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Oncogene. 33, 116–128.

  84. Zhang S., Mercado-Uribe I., Sood A., Bast R.C., Liu J. (2016) Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells. Genes Cancer. 7, 60–72.

  85. Kozlov A.P. (2014) Evolution by Tumor Neofunctionalization. Elsevier/Acad. Press. 248 p.

  86. Kozlov A.P. (2019) The role of heritable tumors in evolution of development: a new theory of carcino-evo-devo. Acta Naturae. 11, 65–72.

  87. Ruiz M., Quiñones A., Martínez-Cuenca M.R., Aleza P., Morillon R., Navarro L., Primo-Millo E., Martínez-Alcántara B. (2016) Tetraploidy enhances the ability to exclude chloride from leaves in Carrizo citrange seedlings. J. Plant Physiol. 205, 1–10.

  88. Bhatta M., Morgounov A., Belamkar V., Wegulo S.N., Dababat A.A., Erginbas-Orakci G., Bouhssini M.E., Gautam P., Poland J., Akci N., Demir L., Wanyera R., Baenziger P.S. (2019) Genome-wide association study for multiple biotic stress resistance in synthetic hexaploid wheat. Int. J. Mol. Sci. 20, 3667.

  89. Yao Y., Carretero-Paulet L., Van de Peer Y. (2019) Using digital organisms to study the evolutionary consequences of whole genome duplication and polyploidy. PLoS One. 14, e0220257.

  90. Keane O.M., Toft C., Carretero-Paulet L., Jones G.W., Fares M.A. (2014) Preservation of genetic and regulatory robustness in ancient gene duplicates of Saccharomyces cerevisiae. Genome Res. 24, 1830–1841.

  91. Carretero-Paulet L., Van de Peer Y. (2020) The evolutionary conundrum of whole-genome duplication. Am. J. Bot. 107, 1101–1105.

  92. Анацкая О.В., Виноградов А.Е., Кудрявцев Б.Н. (1998) Уровни плоидности миоцитов в разных отделах сердца птиц. Цитология. 5, 359–371.

  93. Anatskaya O.V., Vinogradov A.E. (2004) Paradoxical relationship between protein content and nucleolar activity in mammalian cardiomyocytes. Genome. 47, 565–578.

  94. Anatskaya O.V., Vinogradov A.E. (2004) Heart and liver as developmental bottlenecks of mammal design: evidence from cell polyploidization. Biol. J. Linn. Soc. 83, 175–186.

  95. Anatskaya O.V., Vinogradov A.E. (2002) Myocyte ploidy in heart chambers of birds with different locomotor activity. J. Exp. Zool. 293, 427–441.

  96. Derks W., Bergmann O. (2020) Polyploidy in cardiomyocytes: roadblock to heart regeneration? Circ. Res. 126, 552–565.

  97. Brodsky V.Y., Sarkisov D.S., Arefyeva A.M., Panova N.W., Gvasava I.G. (1994) Polyploidy in cardiac myocytes of normal and hypertrophic human hearts; range of values. Virchows Arch. 424, 429–435.

  98. Leone M., Engel F.B. (2019) Advances in heart regeneration based on cardiomyocyte proliferation and regenerative potential of binucleated cardiomyocytes and polyploidization. Clin. Sci. (Lond). 133, 1229–1253.

  99. Anatskaya O.V., Sidorenko N.V., Beyer T.V., Vinogradov A.E. (2010) Neonatal cardiomyocyte ploidy reveals critical windows of heart development. Int. J. Cardiol. 141, 81–91.

  100. Анацкая О.В., Сидоренко Н.В., Бейер Т.В., Виноградов А.Е. (2010) Неонатальный гастроэнтерит как причина долговременной атрофии, деформации и необратимой гиперполиплоидизации кардиомиоцитов. Кардиология. 10(12), 35–44.

  101. Anatskaya O.V., Sidorenko N.V., Vinogradov A.E., Beyer T.V. (2007) Impact of neonatal cryptosporidial gastroenteritis on epigenetic programming of rat hepatocytes. Cell Biol. Int. 31, 420–427.

  102. Anatskaya O.V., Sidorenko N.V., Matveev I.V., Kropotov A.V., Vinogradov A.E. (2012) Remodeling of rat cardiomyocytes after neonatal cryptosporidiosis. II. Deformation, excessive polyploidization, and HIF-1α overexpression. Cell Tiss. Biol. 6, 472–484.

  103. Anatskaya O.V., Matveev I.V., Sidorenko N.V., Kharchenko M.V., Kropotov A.V., Vinogradov A.E. (2013) Changes in the heart of neonatal rats after cryptosporidial gastroenteritis of different degrees of severity. J. Evol. Biochem. Phys. 49, 509–518.

  104. Bensley J.G., Stacy V.K., De Matteo R., Harding R., Black M.J. (2010) Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease. Eur. Heart J. 31, 2058–2066.

  105. Filatova N.A., Knyazev N.A., Skarlato S.O., Anatskaya O.V., Vinogradov A.E. (2018) Natural killer cell activity irreversibly decreases after Cryptosporidium gastroenteritis in neonatal mice. Parasite Immunol. 40, e12524.

  106. Mayfield-Jones D., Washburn J.D., Arias T., Edger P.P., Pires J.C., Conant G.C. (2013) Watching the grin fade: tracing the effects of polyploidy on different evolutionary time scales. Semin. Cell Dev. Biol. 24, 320–331.

  107. Vinogradov A.E., Anatskaya O.V., Kudryavtsev B.N. (2001) Relationship of hepatocyte ploidy levels with body size and growth rate in mammals. Genome. 44, 350–360.

  108. Anatskaya O.V., Vinogradov A.E., Kudryavtsev B.N. (2001) Cardiomyocyte ploidy levels in birds with different growth rates. J. Exp. Zool. 289, 48–58.

  109. Анацкая О.В., Эренпрейса Е.А., Никольский Н.Н., Виноградов А.Е. (2015) Попарно-перекрестное сравнение транскриптомов млекопитающих в исследовании влияния полиплоидии на активность экспрессии генных модулей развития. Цитология. 57, 899–908.

  110. Vinogradov A.E. (2005) Genome size and chromatin condensation in vertebrates. Chromosoma. 113, 362–369.

  111. Pienta K.J., Hammarlund E.U., Axelrod R., Amend S.R., Brown J.S. (2020) Convergent evolution, evolving evolvability, and the origins of lethal cancer. Mol. Cancer Res. 18, 801–810.

  112. Lopez-Sánchez L.M., Jimenez C., Valverde A., Hernandez V., Peñarando J., Martinez A., Lopez-Pedrera C., Muñoz-Castañeda J.R., De la Haba-Rodríguez J.R., Aranda E., Rodriguez-Ariza A. (2014) CoCl2, a mimic of hypoxia, induces formation of polyploid giant cells with stem characteristics in colon cancer. PLoS One. 9, e99143.

  113. Mirzayans R., Murray D. (2020) Intratumor heterogeneity and therapy resistance: contributions of dormancy, apoptosis reversal (Anastasis) and cell fusion to disease recurrence. IJMS. 21, 1308.

  114. Mirzayans R., Andrais B., Murray D. (2018) Roles of polyploid/multinucleated giant cancer cells in metastasis and disease relapse following anticancer treatment. Cancers (Basel). 10, 118.

  115. Amend S.R., Torga G., Lin K.-C., Kostecka L.G., de Marzo A., Austin R.H., Pienta K.J. (2019) Polyploid giant cancer cells: unrecognized actuators of tumorigenesis, metastasis, and resistance. Prostate. 79, 1489–1497.

  116. Anatskaya O.V., Vinogradov A.E. (2010) Somatic polyploidy promotes cell function under stress and energy depletion: evidence from tissue-specific mammal transcriptome. Funct. Integr. Genomics. 10, 433–446.

  117. Vazquez-Martin A., Anatskaya O.V., Giuliani A., Erenpreisa J., Huang S., Salmina K., Inashkina I., Huna A., Nikolsky N.N., Vinogradov A.E. (2016) Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature. Oncotarget. 7, 75235–75260.

  118. Anatskaya O.V., Erenpreisa J., Giuliani A., Tsimok-ha A.S., Salmina K., Vinogradov A.E. (2020) Polyploidy related induction of morphogenetic signaling is mediated via proteasome pathway. Cell Death Discov. 6, RPC02.

  119. Cеленина А.В., Цимоха А.С., Томилин А.Н. (2017) Протеасомы в регуляции белкового гомеостаза плюрипотентных стволовых клеток. Acta Naturae. 9, 39–47.

  120. Lazzeri E., Angelotti M.L., Conte C., Anders H.-J., Romagnani P. (2019) Surviving acute organ failure: cell polyploidization and progenitor proliferation. Trends Mol. Med. 25, 366–381.

  121. Donne R., Saroul-Aïnama M., Cordier P., Celton-Morizur S., Desdouets C. (2020) Polyploidy in liver development, homeostasis and disease. Nat. Rev. Gastroenterol. Hepatol. 17, 391–405.

  122. Chikhirzhina E., Starkova T., Polyanichko A. (2018) The role of linker histones in chromatin structural organization. 1. H1 family histones. Biophysics. 63, 858–865.

  123. Chikhirzhina E.V., Starkova T.Yu., Polyanichko A.M. (2020) The role of linker histones in chromatin structural organization. 2. Interaction with DNA and nuclear proteins. Biophysics. 65, 202–212.

  124. Chikhirzhina E., Starkova T., Beljajev A., Polyanichko A., Tomilin A. (2020) Functional diversity of non-histone chromosomal protein HmgB1. Int. J. Mol. Sci. 21, 7948.

  125. Старкова Т.Ю., Артамонова Т.О., Ермакова В.В., Чихиржина Е.В., Ходорковский М.А., Томилин А.Н. (2019) Профиль посттранскрипционных модификаций гистона Н1 в хроматине эмбриональных ставоловых клеток мыши. Acta Naturae.11, 82–91.

  126. Gilsbach R., Preissl S., Grüning B.A., Schnick T., Burger L., Benes V., Würch A., Bönisch U., Günther S., Backofen R., Fleischmann B.K., Schübeler D., Hein L. (2014) Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease. Nat. Commun. 5, 5288.

  127. Silva I.S., Ghiraldini F.G., Veronezi G.M.B., Mel-lo M.L.S. (2018) Polyploidy and nuclear phenotype characteristics of cardiomyocytes from diabetic adult and normoglycemic aged mice. Acta Histochem. 120, 84–94.

  128. Bian F., Gao F., Kartashov A.V., Jegga A.G., Barski A., Das S.K. (2016) Polycomb repressive complex 1 controls uterine decidualization. Sci. Rep. 6, 26061.

  129. Han P., Li W., Yang J., Shang C., Lin C.H., Cheng W., Hang C.T., Cheng H.L., Chen C.H., Wong J., Xiong Y., Zhao M., Drakos S.G., Ghetti A., Li D.Y., Bernstein D., Chen H.S., Quertermous T., Chang C.P. (2016) Epigenetic response to environmental stress: assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts. Biochim. Biophys. Acta. 1863, 1772–1781.

  130. Bernstein B.E., Mikkelsen T.S., Xie X., Kamal M., Huebert D.J., Cuff J., Fry B., Meissner A., Wernig M., Plath K., Jaenisch R., Wagschal A., Feil R., Schreiber S.L., Lander E.S. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 125, 315–326.

  131. Malik A., Korol A., Weber M., Hankeln T., Avivi A., Band M. (2012) Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis. BMC Genomics. 13, 615.

  132. Ma S., Upneja A., Galecki A., Tsai Y.M., Burant C.F., Raskind S., Zhang Q., Zhang Z.D., Seluanov A., Gorbunova V., Clish C.B., Miller R.A., Gladyshev V.N. (2016) Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity. Elife. 5, e19130.

  133. Ma S., Gladyshev V.N. (2017) Molecular signatures of longevity: Insights from cross-species comparative studies. Semin. Cell Dev. Biol. 70, 190–203.

  134. Tsimokha A.S., Kulichkova V.A., Karpova E.V., Zaykova J.J., Aksenov N.D., Vasilishina A.A., Kropotov A.V., Antonov A., Barlev N.A. (2014) DNA damage modulates interactions between microRNAs and the 26S proteasome. Oncotarget. 5, 3555–3567.

  135. Margulis B., Tsimokha A., Zubova S., Guzhova I. (2020) Molecular chaperones and proteolytic machineries regulate protein homeostasis in aging cells. Cells. 9, 1308.

  136. Blanc G., Wolfe K.H. (2004) Widespread paleopolyploidy in model plant species inferred from age distributions of duplicate genes. Plant Cell. 16, 1667–1678.

  137. Fotiou E., Williams S., Martin-Geary A., Robertson D.L., Tenin G., Hentges K.E., Keavney B. (2019) Integration of large-scale genomic data sources with evolutionary history reveals novel genetic loci for congenital heart disease. Circ. Genom. Precis. Med. 12, 442–451.

  138. Yamasaki M., Makino T., Khor S.S., Toyoda H., Miyagawa T., Liu X., Kuwabara H., Kano Y., Shimada T., Sugiyama T., Nishida H., Sugaya N., Tochigi M., Otowa T., Okazaki Y., Kaiya H., Kawamura Y., Miyashita A., Kuwano R., Kasai K., Tanii H., Sasaki T., Honda M., Tokunaga K. (2020) Sensitivity to gene dosage and gene expression affects genes with copy number variants observed among neuropsychiatric diseases. BMC Med. Genomics. 13, 55.

  139. Arbabian A., Iftinca M., Altier C., Singh P.P., Isambert H., Coscoy S. (2020) Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells. Channels (Austin). 14, 101–109.

  140. Illidge T.M., Cragg M.S., Fringes B., Olive P., Erenpreisa J.A. (2000) Polyploid giant cells provide a survival mechanism for p53 mutant cells after DNA damage. Cell Biol. Int. 24, 621–633.

  141. Sundaram M., Guernsey D.L., Rajaraman M.M., Rajaraman R. (2004) Neosis: a novel type of cell division in cancer. Cancer Biol. Ther. 3, 207–218.

  142. Puig P.-E., Guilly M.N., Bouchot A., Droin N., Cathelin D., Bouyer F., Favier L., Ghiringhelli F., Kroemer G., Solary E., Martin F., Chauffert B. (2008) Tumor cells can escape DNA-damaging cisplatin through DNA endoreduplication and reversible polyploidy. Cell Biol. Int. 32, 1031–1043.

  143. Lagadec C., Vlashi E., Della Donna L., Dekmezian C., Pajonk F. (2012) Radiation-induced reprogramming of breast cancer cells: radiation-induced cancer stem cells. Stem Cells. 30, 833–844.

  144. Weihua Z., Lin Q., Ramoth A.J., Fan D., Fidler I.J. (2011) Formation of solid tumors by a single multinucleated cancer cell. Cancer. 117, 4092–4099.

  145. Sikora E., Czarnecka-Herok J., Bojko A., Sunderland P. (2020) Therapy-induced polyploidization and senescence: coincidence or interconnection? Semin. Cancer Biol. S1044-579X(20)30253-4. https://doi.org/10.1016/j.semcancer.2020.11.015

  146. Patterson M., Swift S.K. (2019) Residual diploidy in polyploid tissues: a cellular state with enhanced proliferative capacity for tissue regeneration? Stem Cells Dev. 28, 1527–1539.

  147. Patterson M., Barske L., Van Handel B., Rau C.D., Gan P., Sharma A., Parikh S., Denholtz M., Huang Y., Yamaguchi Y., Shen H., Allayee H., Crump J.G., Force T.I., Lien C.L., Makita T., Lusis A.J., Kumar S.R., Sucov H.M. (2017) Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nat. Genet. 49, 1346–1353.

  148. Gan P., Patterson M., Velasquez A., Wang K., Tian D., Windle J.J., Tao G., Judge D.P., Makita T., Park T.J., Sucov H.M. (2019) Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency. PLoS Genet. 15, e1008354.

  149. Анацкая О.В., Рунов А.Л., Вонский М.С., Харченко М.В., Пономарцев С.В., Елмуратов А.У., Виноградов А.Е. (2019) Нарушение постнатального органогенеза сердца после неонатальной непереносимости лактозы. Гены и клетки. 14, 21–22.

  150. Salman-Minkov A., Sabath N., Mayrose I. (2016) Whole-genome duplication as a key factor in crop domestication. Nat. Plants. 2, 16115.

  151. Guo H., Mendrikahy J.N., Xie L., Deng J., Lu Z., Wu J., Li X., Shahid M.Q., Liu X. (2017) Transcriptome analysis of neo-tetraploid rice reveals specific differential gene expressions associated with fertility and heterosis. Sci. Rep. 7, 40139.

  152. Julião S.A., Ribeiro C.D.V., Lopes J.M.L., de Matos E.M., Reis A.C., Peixoto P.H.P., Machado M.A., Azevedo A.L.S., Grazul R.M., de Campos J.M.S., Viccini L.F. (2020) Induction of synthetic polyploids and assessment of genomic stability in Lippia alba. Front. Plant Sci. 11, 292.

  153. Vinogradov A.E., Borkin L.J., Günther R., Rosa-nov J.M. (1991) Two germ cell lineages with genomes of different species in one and the same animal. Hereditas. 114, 245–251.

  154. Vinogradov A.E., Borkin L.J., Günther R., Rosanov J.M. (1990) Genome elimination in diploid and triploid Rana esculenta males: cytological evidence from DNA flow cytometry. Genome. 33, 619–627.

Дополнительные материалы отсутствуют.