The most common causes of chronic liver disease (CLD) are chronic hepatitis B or C virus (HBV/HCV) infections, alcohol abuse and non-alcoholic fatty liver disease (NAFLD) . Before undergoing meiosis, the chromosome number is doubled during gamete formation. Unable to load your collection due to an error, Unable to load your delegates due to an error. Piero J., Ramrez-Anguita J.M., Sach-Pitarch J., Ronzano F., Centeno E., Sanz F., Furlong L.I. The fundamental nature of the above-described properties of somatic polyploidy is supported by the fact that similar gene modules are enriched in the ohnologs of polyploid organisms, such as the yeast, Arabidopsis, amphibians, and bony fishes [5,120,121]. Niculescu V.F. Domesticated plants have gone through more polyploidization events than their wild relatives [40]. Atlas of mammalian chromosomes. Autotetraploid Rice Methylome Analysis Reveals Methylation Variation of Transposable Elements and Their Effects on Gene Expression. These observations suggest practical applications as certain unicellular-specific drugs can be applied for the treatment of cancer [60]. The liver is one of the few mammalian organs that display changes in polyploidy during homeostasis, regeneration and in response to damage. Child Health, Developmental Plasticity, and Epigenetic Programming. In slowly renewing or terminally differentiated organs of warm-blooded animals (e.g., heart and liver), neonatal genome accumulation is irreversible [77,106]. Using the allozyme electrophoresis technique, studies of natural populations from diverse plant groups revealed a number of previously unrecognized autopolyploids, including Tolmiea menziesii (Saxifragaceae) ( Soltis and Soltis, 1989b ), Heuchera micrantha (Saxifragaceae) ( Soltis et al., 1989 ), Heuchera grossulariifolia (Saxifragaceae) ( Wolf . Before For example, in the yeast interactome, the proteins encoded by ohnologs have a lower number of protein interactions compared to the single-gene duplicates and genes without duplicates (i.e., genes that lost the second ohnolog) [28]. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health. NCG: p < 1046, DGN: p < 10107. In some cases, damage-induced polyploidization is only temporary salvation in an emergency. The https:// ensures that you are connecting to the Soppa J. Polyploidy and Community Structure. However, whatever evolutionary perspectives of polyploids may be, natural selection is not teleological and works only for immediate adaptation. Opin. Microglial Memory of Early Life Stress and Inflammation: Susceptibility to Neurodegeneration in Adulthood. PluriNet: enrichment p < 1051 in Up, underrepresentation p < 1011 in Down. Zhou L., Gui J. Intriguingly, polyploidization by fusion of different cell types (epigenetic hybridization), which is frequently observed both in normal and cancer tissues [4,63], strikingly resembles allopolyploidization (genetic hybridization) in the evolution and agri/aquaculture described above. Polyploidy is widespread in whole organisms and individual cells of multicellular tissues. The Phenotypic Plasticity of Duplicated Genes in Saccharomyces Cerevisiae and the Origin of Adaptations. These facts suggest that subfunctionalization was a prevailing trend in the evolution of retained ohnologs, and was accompanied by regulatory specialization. These mutations in apical meristems results in doubling of growth in plants. Polyploidy, also known as whole-genome amplification, is a condition in which the organism has more than two basic sets of chromosomes. The pre-WGD ohnologs show enrichment in the synapse genes and underrepresentation in the chromatin genes, whereas the post-WGD ohnologs show a stronger enrichment in the chromatin genes than in the synapse genes, with significant difference in these enrichments (Figure 2A,B). The predominant retention of regulatory and developmental genes subsequent to WGD can take place as relaxed selection allowed duplicated networks to be rewired, and to evolve novel functionality, thereby increasing biological complexity [5]. Polyploids arise when a rare mitotic or meiotic catastrophe, such as nondisjunction, causes the formation of gametes that have a complete set of. Cell Death Dis. (C,D)pluripotency signature (PluriNet) and regulation of multicellular organismal development GO:2000026 (MC development). The domesticated organisms are mostly allopolyploids (i.e., the results of polyploidization associated with hybridization). Whole-Genome Doubling Confers Unique Genetic Vulnerabilities on Tumour Cells. It is also called trisomy 21. It depends on the second fundamental copying type, which is orthogonal to the first. Cell-Cycle Dependence of Transcriptome Gene Modules: Comparison of Regression Lines. The relationship between polyploidy and the decrease in the organ functional potential makes the factors regulating genome accumulation in somatic cells particularly important. R. Soc. Mollova M., Bersell K., Walsh S., Savla J., Das L.T., Park S.-Y., Silberstein L.E., Dos Remedios C.G., Graham D., Colan S., et al. Figure 5 illustrates the most important common features of polyploidy existing at various physiological conditions and in different biological contexts. Singh P.P., Isambert H. OHNOLOGS v2: A Comprehensive Resource for the Genes Retained from Whole Genome Duplication in Vertebrates. Human monogenic disease genes in the OMIM database are enriched in ohnologs [53]. Molecular Signatures of Longevity: Insights from Cross-Species Comparative Studies. Gene-dosage sensitivity has been of increasing interest as it might provide a clue for many pathologies [53]. Sikora E., Czarnecka-Herok J., Bojko A., Sunderland P. Therapy-Induced Polyploidization and Senescence: Coincidence or Interconnection? Although polyploidy is less common in mammals than in plants, polyploid cells are generated in different tissues. Polyploidy plays an essential role during normal development and could also contribute to human diseases. Garcia-Lozano M., Natarajan P., Levi A., Katam R., Lopez-Ortiz C., Nimmakayala P., Reddy U.K. Altered Chromatin Conformation and Transcriptional Regulation in Watermelon Following Genome Doubling. 18, 658667 (2006). Mller M., May S., Bird T.G. In: Larramendy M., Soloneski S., editors. Known disorders include Charcot-Marie-Tooth disease type 1A, which can be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17. Large-scale species radiation in a given taxonomic group typically follows polyploidization events, indicating the potential of polyploidization for speciation [36]. Received 2022 Feb 24; Accepted 2022 Mar 22. The upregulation of G2/M checkpoint genes with downregulation of G1/S checkpoint was found in polyploid breast cancer cells (called G2/M vs. G1/S checkpoint inversion) using single-cell transcriptomes with the control for cell cycle activity [59]. In birds and mammals, polyploids can also arise after conception, yet die in early development [22]. Murine rodents have weaker cell cycle control compared to larger mammals due to the evolutionary balance in rodents being biased in favor of the rapid development at the expense of accuracy and reliability of cellular processes [159,160]. By increasing the amount of information and the scope of genetic variation, it increases tolerance to a wide range of stressful conditions, promotes biological plasticity and adaptation to new ecological niches, and masks harmful effects of mutations. Hu H., Miao Y.-R., Jia L.-H., Yu Q.-Y., Zhang Q., Guo A.-Y. Newcomb R., Dean E., McKinney B.J., Alvarez J.V. Julio S.A., do Ribeiro C.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., et al. The Dualistic Origin of Human Tumors. These results were obtained on the bulk tissues and without control for cell cycle activity. The corresponding values for a sedentary swine (Sus scrofa) that is mature-born and mobile from birth, are 8.5 n and 0.25% [71,82]. Genetic plasticity of the polyploid genome and multicopy genes present a special advantage for domestication [36]. Gjelsvik K.J., Besen-McNally R., Losick V.P. Polyploidy, that is having multiple sets of chromosomes as a consequence of whole-genome duplication (WGD), has been studied for over 100 years, especially in flowering plants, dating back to the classic work of Hugo de Vries, jvind Winge, Cyril Darlington, and G. Ledyard Stebbins, Jr (Soltis et al., 2014a).Because of the well-known detrimental effects arising from doubling one . Induction of Synthetic Polyploids and Assessment of Genomic Stability in Lippia Alba. The upregulation of the unicellular giant cluster suggests that oncogenesis is not just an alteration in a few genes but the switching to ancient unicellular programs (when cells tend to behave as independent organisms). Polyploidy facilitates chromosomal instability, which leads to aneuploidy and chromosome abnormalities increasing the probability of transformation [50,63]. (2015). In addition, polyploidization plays a special role in the increase in complexity due to the certain properties of cellular network growth in the case of WGD as compared with the single-gene duplication [12], which will be discussed below. Under genotoxic conditions, when entering in mitosis inevitably leads to cell death, polyploidy is an adaptive replacement for a completed cell cycle. The studies of cardiomyocyte ploidy in more than 80 species of birds and mammals indicated that the degree of polyploidization reflects cardiac functional load during growth [82,104,105,109]. (C,D)transcription factors (TF) and ion transmembrane transporter activity GO:0015075 (ITT). Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome. Cell ploidy in the adult state positively correlated with the neonatal functional load (as polyploidization is caused by the overlapping of cell function with proliferation during growth). . Anatskaya O.V., Vinogradov A.E. Polyploid cancer cells show a general increase in adaptivity, which is reminiscent of the rapid growth, stress resistance, and the evolutionary plasticity of polyploid organisms. MC development: underrepresentation p < 105 in Up; enrichment p < 1028 in Down. Anatskaya O.V., Sidorenko N.V., Beyer T.V., Vinogradov A.E. Vinogradov A.E. Ohnologs are also highly enriched in the genes from the Disease Gene Network and the Network of Cancer Genes, which involve diseases with more complex etiologies (Figure 3). Ecol. Altogether, these data indicate that polyploidy can be involved in developmental programming as it is irreversible, responds to programming stimuli during the critical period of development, changes cell phenotype, and weakens cell function, thus meeting all basic criteria of developmental programming. Polyploids show a higher resistance to environmental stress and diseases [37,38]. The great diversity of vertebrates, which appeared after the two WGD rounds followed by sub- and neofunctionalization of ohnologs, can be considered as an extension of Cambrian explosion in the vertebrate lineage (reflected in the plateau of interactome centrality). 7. Cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration [4]. Michiue T., Yamamoto T., Yasuoka Y., Goto T., Ikeda T., Nagura K., Nakayama T., Taira M., Kinoshita T. High Variability of Expression Profiles of Homeologous Genes for Wnt, Hh, Notch, and Hippo Signaling Pathways in Xenopus Laevis. In other words, the polyploid cell or organism has three or more times the haploid chromosome number. Lazzeri E., Angelotti M.L., Conte C., Anders H.-J., Romagnani P. Surviving Acute Organ Failure: Cell Polyploidization and Progenitor Proliferation. Hepatocyte polyploidization and its association with pathophysiological processes. Heart and Liver as Developmental Bottlenecks of Mammal Design: Evidence from Cell Polyploidization. Polyploidy is defined on the basis of the. Liberzon A., Birger C., Thorvaldsdttir H., Ghandi M., Mesirov J.P., Tamayo P. The Molecular Signatures Database (MSigDB) Hallmark Gene Set Collection. AnimalTFDB 3.0: A Comprehensive Resource for Annotation and Prediction of Animal Transcription Factors. Accessibility Polyploidy frequently arises during tissue development and repair, and in age-associated diseases, such as cancer. 2023 Mar;10(7):e2205855. Vinogradov A.E. Lurbe E., Ingelfinger J. Developmental and Early Life Origins of Cardiometabolic Risk Factors: Novel Findings and Implications. The experimental model of gastroenteritis was used as gastroenteritis triggers developmental programming factors, including inflammation, growth retardation, and malabsorption, and as gastroenteritis is a major cause of diseases in toddlers, infants, and children [149,150,151]. Moritz C., Bi K. Spontaneous Speciation by Ploidy Elevation: Laboratory Synthesis of a New Clonal Vertebrate. Depending on mitotic potential of cells and tissues, polyploidy can be dangerous or beneficial. Zhang S., Zhou K., Luo X., Li L., Tu H.-C., Sehgal A., Nguyen L.H., Zhang Y., Gopal P., Tarlow B.D., et al. Polyploid cancer cells show a general increase in adaptivity, which is reminiscent of the rapid growth, stress resistance, and the evolutionary plasticity of polyploid organisms. Vinogradov A.E., Anatskaya O.V. Malik A., Korol A., Weber M., Hankeln T., Avivi A., Band M. Transcriptome Analysis of the Spalax Hypoxia Survival Response Includes Suppression of Apoptosis and Tight Control of Angiogenesis. Its consequences are diverse and clearly different between systems. Changes in the Heart of Neonatal Rats after Cryptosporidial Gastroenteritis of Different Degrees of Severity. Gluckman P.D., Hanson M.A., Low F.M. DNA Content, Ploidy Level and Number of Nuclei in the Human Heart after Myocardial Infarction. Polyploidy in tumors is associated with resistance to radio/chemotherapy and poor prognosis [65,66]. Although polyploidy is less common in mammals than in plants, polyploid cells are generated in different tissues. ii- polyploidy: The condition in which a normally diploid cell or organism acquires one or more additional sets of chromosomes is called polyploidy. Polyploid cancer cells show a general increase in adaptivity, which is reminiscent of the rapid growth, stress resistance, and the evolutionary plasticity of polyploid organisms. Many artificial polyploids are utilized commercially in aquaculture and most of them were created from natural polyploid fishes and shellfishes, especially cyprinids and salmonids [44]. Endopolyploidy as a Potential Driver of Animal Ecology and Evolution. In mammals, polyploid cells appear during normal postnatal organogenesis. The most convincing evidence was obtained for cardiovascular diseases that are the most susceptible to developmental programming. Polyploidy: An Evolutionary and Ecological Force in Stressful Times. PWS, which occurs at approximately the same frequency, can be caused by a deletion on the long arm of chromosome 15 (Figure 7), although other chromosomal abnormalities can also lead to the syndrome. The bivalent genes (Fantom-confirmed) were from [30]. [1] Below we consider these points in more detail. However, polyploidy-associated regeneration has also species-specific effects. Chromatin: underrepresentation p < 0.01 in pre-WGD, enrichment p < 1061 in post-WGD. In these slowly renewing organs, polyploidy may be the only way to maintain functionality under stressful conditions [72]. Macrophage polyploidization during inflammation is also caused by DNA damage [96]. 2023 Mar 31;24(7):6546. doi: 10.3390/ijms24076546. The site is secure. Mol Ther Methods Clin Dev. Inactivating of Lamin B decreases metaphase progression and increases genetic instability due to the impaired attachment of chromosomes to the mitotic spindle fibers [95,127]. Polyploid organisms have multiple sets of chromosomes as a result of undergoing whole-genome duplication (WGD), which can be caused, for instance, by abnormal cell division.The study of polyploidy . Silva I.S., Ghiraldini F.G., Veronezi G.M.B., Mello M.L.S. Consequently, factors regulating this process in adult animals should be sought in early postnatal development (in childhood). Cause of Polyploidy One of the major causes of ploidy is due to the non-disjunction of sister chromatids. We hypothesized that somatic polyploidy can be one of the epigenetic mechanisms of developmental programming in slowly renewing and terminally differentiated organs. Allopolyploidization presents a way for new organisms formation. Salman-Minkov A., Sabath N., Mayrose I. Whole-Genome Duplication as a Key Factor in Crop Domestication. We also provide an overview of current knowledge about the mechanisms of hepatocyte polyploidization, its biological importance and the fate of polyploid hepatocytes during liver tumorigenesis. In the human interactome, the more ancient genes have a higher local and global centrality compared with newer genes, which indicates a gradual core-to-periphery evolutionary growth of the interactome [12]. It is known that polyploidy is associated with the switching of metabolism to the energy-saving mode [8,152]. To elucidate this point, the key features of early postnatal development (growth rate, degree of maturity at birth, type of development, metabolic rate) were compared in the large-scale studies of mammals and birds with different polyploidization of cardiomyocytes [71,82,104]. These studies show sufficient evidence that . Paradoxically, albeit in normal tissues polyploidization frequently accompanies differentiation [1,68], polyploidy in tumors is associated with the features of fetality and stemness [50,63]. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). The syndrome is often recognized before birth during an ultrasound or . Wen Z, Lin YH, Wang S, Fujiwara N, Rong R, Jin KW, Yang DM, Yao B, Yang S, Wang T, Xie Y, Hoshida Y, Zhu H, Xiao G. Genes (Basel). Cell 131, 452462 (2007). The https:// ensures that you are connecting to the Thus, polyploid cells arise in normal organogenesis of heart, neuronal glia, cerebellum, neocortex, retina, liver, placenta, blood vessels, skin, blood, and other organs [3,22,71,72,73,74] and in atherosclerosis, neurodegenerative disorders, cardiovascular diseases, wound healing, inflammation, diabetes, cancer, and other pathologies [1,7,8,72,74,75,76,77,78,79,80]. In the human liver, approximately 30% of hepatocytes are polyploid. The regulation of polyploid cell growth by Hippo signaling is a crucial, but more poorly understood, factor in organ size control. Thus, the interactome complexity becomes higher in the case of growth by means of WGD, as compared with the growth by single-gene duplicates. It may be fraught with genomic instability leading to oncogenesis. One of the main problems, which new polyploids encounter, is the disturbance of chromosome pairing in meiosis. Aneuploidy occurs when the number of chromosomes a cell has doesn't equal 46. There are also opinions that genomic duplications are neutral as polyploid cells can be an approximate equivalent to the corresponding number of diploid cells [91]. A. This is especially evident in the heart, where polyploidy caused by stress and hyperfunction leads to the replacement of myosin heavy chain (fast, adult, and ATP costly) with myosin heavy chain (slow, embryonic, and ATP economical) [75,153]. For the heart, the functional potential was estimated by the organ mass relative to body mass (heart index), for the liver, by the metabolic scope (i.e., the difference between the basal and maximal metabolic rate). Miles D.M., Desdouets C., Gli V. Histone Stress: An Unexplored Source of Chromosomal Instability in Cancer? Polyploidization leads to long-term consequences both in evolution (organismal) and ontogenesis (somatic) [1]. Du K., Stck M., Kneitz S., Klopp C., Woltering J.M., Adolfi M.C., Feron R., Prokopov D., Makunin A., Kichigin I., et al. FOIA Dujon A.M., Aktipis A., Alix-Panabires C., Amend S.R., Boddy A.M., Brown J.S., Capp J.-P., DeGregori J., Ewald P., Gatenby R., et al. Cardiomyocytes of precocious mammals and birds, which are relatively mature and mobile from hatching or birth, contain 1.6 fold more genomes than cardiomyocytes of altricious species of similar weight, which are helpless at hatching or birth and show weak mobility during growth [82,104]. In contrast, runaway unicellularity results in cancer when cells tend to behave as independent evolutionary units. Cytogenetics-Classical and Molecular Strategies for Analysing Heredity Material. Polyploidization is followed by rediploidization, i.e., the process of converting a polyploid chromosome set into a diploid one. In addition, in rapidly renewing tissues with high proliferative potential, the multinuclear and binuclear polyploid cells can give rise to lower ploidy cells with manifestations of stemness. Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart.... 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