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International Journal of Molecular... Jun 2023Crop genetic diversity is essential for adaptation and productivity in agriculture. A previous study revealed that poor allele diversity in wheat commercial cultivars is...
Crop genetic diversity is essential for adaptation and productivity in agriculture. A previous study revealed that poor allele diversity in wheat commercial cultivars is a major barrier to its further improvement. Homologs within a variety, including paralogs and orthologs in polyploid, account for a large part of the total genes of a species. Homolog diversity, intra-varietal diversity (IVD), and their functions have not been elucidated. Common wheat, an important food crop, is a hexaploid species with three subgenomes. This study analyzed the sequence, expression, and functional diversity of homologous genes in common wheat based on high-quality reference genomes of two representative varieties, a modern commercial variety Aikang 58 (AK58) and a landrace Chinese Spring (CS). A total of 85,908 homologous genes, accounting for 71.9% of all wheat genes, including inparalogs (IPs), outparalogs (OPs), and single-copy orthologs (SORs), were identified, suggesting that homologs are an important part of the wheat genome. The levels of sequence, expression, and functional variation in OPs and SORs were higher than that of IPs, which indicates that polyploids have more homologous diversity than diploids. Expansion genes, a specific type of OPs, made a great contribution to crop evolution and adaptation and endowed crop with special characteristics. Almost all agronomically important genes were from OPs and SORs, demonstrating their essential functions for polyploid evolution, domestication, and improvement. Our results suggest that IVD analysis is a novel approach for evaluating intra-genomic variations, and exploitation of IVD might be a new road for plant breeding, especially for polyploid crops, such as wheat.
Topics: Triticum; Domestication; Plant Breeding; Polyploidy; Agriculture; Genome, Plant; Evolution, Molecular
PubMed: 37373363
DOI: 10.3390/ijms241210217 -
Yeast (Chichester, England) Nov 2014Eukaryotic organisms maintain karyotypes with constant chromosome number, but polyploid cells that contain more than two sets of chromosomes can frequently be found. On... (Review)
Review
Eukaryotic organisms maintain karyotypes with constant chromosome number, but polyploid cells that contain more than two sets of chromosomes can frequently be found. On the one hand, polyploidization is likely to provide some beneficial effects, as naturally occurring polyploid cells can be readily found. On the other hand, polyploidization profoundly affects cell physiology, which may be detrimental to cells. Additionally, polyploidy leads often to aneuploidy and diversification of genetic information; therefore, it has always been considered a prominent driving force in evolution. Recently tetraploid-derived aneuploidy was suggested as a possible mechanism for resistance to fungicides. Another prominent example of the effects of tetraploid-derived aneuploidy is cancer, in which up to one-third of tumours likely originate through tetraploid intermediates. Studying the cellular consequences of polyploidization in human cells is challenging. In contrast, polyploid and aneuploid cells can be easily generated and analysed in the budding yeast Saccharomyces cerevisiae as well as in other yeast species. This, together with the naturally occurring yeast polyploids and aneuploids, provides a valuable model to study the effects of abnormal chromosome numbers on cellular physiology. Thus, the yeast model may provide novel insights into the general mechanisms of genomic instability in eukaryotes and improve our understanding of the consequences of ploidy changes and their relevance for disease.
Topics: Aneuploidy; Cell Physiological Phenomena; Genomic Instability; Polyploidy; Saccharomyces
PubMed: 25155743
DOI: 10.1002/yea.3037 -
Seminars in Cancer Biology Jun 2022Senescence is a tumor suppressor response that prevents the proliferation of mutated cells and alert the immune system for their elimination. However, this program is... (Review)
Review
Senescence is a tumor suppressor response that prevents the proliferation of mutated cells and alert the immune system for their elimination. However, this program is not perfect and with time additional genetic and epigenetic changes can impair tumor suppression and promote cancer progression both in cell autonomous and non-cell autonomous manners. A polyploid barrier is implemented in senescent cells to further prevent cell expansion but polyploid cells can generate highly malignant tumor cells via de-polyploidization. The nuclear lamina can act as an additional fail safe to prevent cancer in these cells and drugs able to stabilize the nuclear lamina may help to treat cancers by preventing senescence escape.
Topics: Cell Cycle; Cell Proliferation; Cellular Senescence; Humans; Neoplasms; Polyploidy
PubMed: 33359514
DOI: 10.1016/j.semcancer.2020.12.017 -
International Journal of Molecular... Jul 2023Single cell biology has revealed that solid tumors and tumor-derived cell lines typically contain subpopulations of cancer cells that are readily distinguishable from... (Review)
Review
Single cell biology has revealed that solid tumors and tumor-derived cell lines typically contain subpopulations of cancer cells that are readily distinguishable from the bulk of cancer cells by virtue of their enormous size. Such cells with a highly enlarged nucleus, multiple nuclei, and/or multiple micronuclei are often referred to as polyploid giant cancer cells (PGCCs), and may exhibit features of senescence. PGCCs may enter a dormant phase (active sleep) after they are formed, but a subset remain viable, secrete growth promoting factors, and can give rise to therapy resistant and tumor repopulating progeny. Here we will briefly discuss the prevalence and prognostic value of PGCCs across different cancer types, the current understanding of the mechanisms of their formation and fate, and possible reasons why these tumor repopulating "monsters" continue to be ignored in most cancer therapy-related preclinical studies. In addition to PGCCs, other subpopulations of cancer cells within a solid tumor (such as oncogenic caspase 3-activated cancer cells and drug-tolerant persister cancer cells) can also contribute to therapy resistance and pose major challenges to the delivery of cancer therapy.
Topics: Humans; Neoplasms; Giant Cells; Polyploidy
PubMed: 37511291
DOI: 10.3390/ijms241411534 -
Cancer Letters May 2024Recurrent chemotherapy-induced senescence and resistance are attributed to the polyploidization of cancer cells that involve genomic instability and poor prognosis due... (Review)
Review
Recurrent chemotherapy-induced senescence and resistance are attributed to the polyploidization of cancer cells that involve genomic instability and poor prognosis due to their unique form of cellular plasticity. Autophagy, a pre-dominant cell survival mechanism, is crucial during carcinogenesis and chemotherapeutic stress, favouring polyploidization. The selective autophagic degradation of essential proteins associated with cell cycle progression checkpoints deregulate mitosis fidelity and genomic integrity, imparting polyploidization of cancer cells. In connection with cytokinesis failure and endoreduplication, autophagy promotes the formation, maintenance, and generation of the progeny of polyploid giant cancer cells. The polyploid cancer cells embark on autophagy-guarded elevation in the expression of stem cell markers, along with triggered epithelial and mesenchymal transition and senescence. The senescent polyploid escapers represent a high autophagic index than the polyploid progeny, suggesting regaining autophagy induction and subsequent autophagic degradation, which is essential for escaping from senescence/polyploidy, leading to a higher proliferative phenotypic progeny. This review documents the various causes of polyploidy and its consequences in cancer with relevance to autophagy modulation and its targeting for therapeutic intervention as a novel therapeutic strategy for personalized and precision medicine.
Topics: Humans; Autophagy; Polyploidy; Cellular Senescence; Neoplasms; Neoplastic Stem Cells; Animals; Epithelial-Mesenchymal Transition
PubMed: 38579893
DOI: 10.1016/j.canlet.2024.216843 -
International Journal of Molecular... Aug 2022Polyploidy, a condition in which more than two sets of chromosomes are present in a cell, is a characteristic feature of hepatocytes. A significant number of hepatocytes... (Review)
Review
Polyploidy, a condition in which more than two sets of chromosomes are present in a cell, is a characteristic feature of hepatocytes. A significant number of hepatocytes physiologically undergo polyploidization at a young age. Polyploidization of hepatocytes is enhanced with age and in a diseased liver. It is worth noting that polyploid hepatocytes can proliferate, in marked contrast to other types of polyploid cells, such as megakaryocytes and cardiac myocytes. Polyploid hepatocytes divide to maintain normal liver homeostasis and play a role in the regeneration of the damaged liver. Furthermore, polyploid hepatocytes have been shown to dynamically reduce ploidy during liver regeneration. Although it is still unclear why hepatocytes undergo polyploidization, accumulating evidence has revealed that alterations in the ploidy in hepatocytes are involved in the pathophysiology of liver cirrhosis and carcinogenesis. This review discusses the significance of hepatocyte ploidy in physiological liver function, liver injury, and liver cancer.
Topics: Hepatocytes; Humans; Liver; Liver Neoplasms; Liver Regeneration; Polyploidy
PubMed: 36012671
DOI: 10.3390/ijms23169409 -
Methods in Molecular Biology (Clifton,... 2023CRISPR/Cas system has been widely used for genome editing in the past few years. Even though it has been performed in many polyploid species to date, its efficient...
CRISPR/Cas system has been widely used for genome editing in the past few years. Even though it has been performed in many polyploid species to date, its efficient accomplishment in these organisms is still a challenge. The presence of multiple homoeologous genes as targets for their editing requires more rigorous work and specific needs to assess successful genome editing. Here, we describe a general stepwise protocol to select target sites, design sgRNAs, indicate vector requirements, and screen CRISPR/Cas9-mediated genome editing in polyploid species.
Topics: Humans; Gene Editing; CRISPR-Cas Systems; Polyploidy
PubMed: 36720828
DOI: 10.1007/978-1-0716-2561-3_24 -
International Journal of Molecular... Feb 2024Organisms with three or more complete sets of chromosomes are designated as polyploids. Polyploidy serves as a crucial pathway in biological evolution and enriches... (Review)
Review
Organisms with three or more complete sets of chromosomes are designated as polyploids. Polyploidy serves as a crucial pathway in biological evolution and enriches species diversity, which is demonstrated to have significant advantages in coping with both biotic stressors (such as diseases and pests) and abiotic stressors (like extreme temperatures, drought, and salinity), particularly in the context of ongoing global climate deterioration, increased agrochemical use, and industrialization. Polyploid cultivars have been developed to achieve higher yields and improved product quality. Numerous studies have shown that polyploids exhibit substantial enhancements in cell size and structure, physiological and biochemical traits, gene expression, and epigenetic modifications compared to their diploid counterparts. However, some research also suggested that increased stress tolerance might not always be associated with polyploidy. Therefore, a more comprehensive and detailed investigation is essential to complete the underlying stress tolerance mechanisms of polyploids. Thus, this review summarizes the mechanism of polyploid formation, the polyploid biochemical tolerance mechanism of abiotic and biotic stressors, and molecular regulatory networks that confer polyploidy stress tolerance, which can shed light on the theoretical foundation for future research.
Topics: Humans; Biological Evolution; Polyploidy; Phenotype; Diploidy
PubMed: 38396636
DOI: 10.3390/ijms25041957 -
Seminars in Cancer Biology Jun 2022Ploidy increase has been shown to occur in different type of tumors and participate in tumor initiation and resistance to the treatment. Polyploid giant cancer cells... (Review)
Review
Ploidy increase has been shown to occur in different type of tumors and participate in tumor initiation and resistance to the treatment. Polyploid giant cancer cells (PGCCs) are cells with multiple nuclei or a single giant nucleus containing multiple complete sets of chromosomes. The mechanism leading to formation of PGCCs may depend on: endoreplication, mitotic slippage, cytokinesis failure, cell fusion or cell cannibalism. Polyploidy formation might be triggered in response to various genotoxic stresses including: chemotherapeutics, radiation, hypoxia, oxidative stress or environmental factors like: air pollution, UV light or hyperthermia. A fundamental feature of polyploid cancer cells is the generation of progeny during the reversal of the polyploid state (depolyploidization) that may show high aggressiveness resulting in the formation of resistant disease and tumor recurrence. Therefore, we propose that modern anti-cancer therapies should be designed taking under consideration polyploidization/ depolyploidization processes, which confer the polyploidization a hidden potential similar to a Trojan horse delayed aggressiveness. Various mechanisms and stress factors leading to polyploidy formation in cancer cells are discussed in this review.
Topics: Cell Nucleus; Giant Cells; Humans; Neoplasm Recurrence, Local; Polyploidy
PubMed: 33727077
DOI: 10.1016/j.semcancer.2021.03.003 -
Trends in Plant Science Dec 2017Mixed-ploidy species harbor a unique form of genomic and phenotypic variation that influences ecological interactions, facilitates genetic divergence, and offers... (Review)
Review
Mixed-ploidy species harbor a unique form of genomic and phenotypic variation that influences ecological interactions, facilitates genetic divergence, and offers insights into the mechanisms of polyploid evolution. However, there have been few attempts to synthesize this literature. We review here research on the cytotype distribution, diversity, and dynamics of intensively studied mixed-ploidy species and consider the implications for understanding mechanisms of polyploidization such as cytotype formation, establishment, coexistence, and post-polyploid divergence. In general, mixed-ploidy species are unevenly represented among families: they exhibit high cytotype diversity, often within populations, and frequently comprise rare and odd-numbered ploidies. Odd-ploidies often occur in association with asexuality. We highlight research hypotheses and opportunities that take advantage of the unique properties of ploidy variation.
Topics: Chromosomes, Plant; Genetic Variation; Plants; Ploidies; Polyploidy
PubMed: 29054346
DOI: 10.1016/j.tplants.2017.09.011