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Genomics May 2022Phasing, and in particular polyploid phasing, have been challenging problems held back by the limited read length of high-throughput short read sequencing methods which... (Review)
Review
Phasing, and in particular polyploid phasing, have been challenging problems held back by the limited read length of high-throughput short read sequencing methods which can't overcome the distance between heterozygous sites and labor high cost of alternative methods such as the physical separation of chromosomes for example. Recently developed single molecule long-read sequencing methods provide much longer reads which overcome this previous limitation. Here we review the alignment-based methods of polyploid phasing that rely on four main strategies: population inference methods, which leverage the genetic information of several individuals to phase a sample; objective function minimization methods, which minimize a function such as the Minimum Error Correction (MEC); graph partitioning methods, which represent the read data as a graph and split it into k haplotype subgraphs; cluster building methods, which iteratively grow clusters of similar reads into a final set of clusters that represent the haplotypes. We discuss the advantages and limitations of these methods and the metrics used to assess their performance, proposing that accuracy and contiguity are the most meaningful metrics. Finally, we propose the field of alignment-based polyploid phasing would greatly benefit from the use of a well-designed benchmarking dataset with appropriate evaluation metrics. We consider that there are still significant improvements which can be achieved to obtain more accurate and contiguous polyploid phasing results which reflect the complexity of polyploid genome architectures.
Topics: Humans; Genome, Human; Sequence Analysis, DNA; Haplotypes; Algorithms; Polyploidy; High-Throughput Nucleotide Sequencing
PubMed: 35483655
DOI: 10.1016/j.ygeno.2022.110369 -
Development (Cambridge, England) Jul 2021Terminally differentiated cells are generally thought to have arrived at their final form and function. Many terminally differentiated cell types are polyploid, i.e....
Terminally differentiated cells are generally thought to have arrived at their final form and function. Many terminally differentiated cell types are polyploid, i.e. they have multiple copies of the normally diploid genome. Mammalian heart muscle cells, termed cardiomyocytes, are one such example of polyploid cells. Terminally differentiated cardiomyocytes are bi- or multi-nucleated, or have polyploid nuclei. Recent mechanistic studies of polyploid cardiomyocytes indicate that they can limit cellular proliferation and, hence, heart regeneration. In this short Spotlight, we present the mechanisms generating bi- and multi-nucleated cardiomyocytes, and the mechanisms generating polyploid nuclei. Our aim is to develop hypotheses about how these mechanisms might relate to cardiomyocyte proliferation and cardiac regeneration. We also discuss how these new findings could be applied to advance cardiac regeneration research, and how they relate to studies of other polyploid cells, such as cancer cells.
Topics: Animals; Heart; Humans; Myocytes, Cardiac; Polyploidy; Regeneration
PubMed: 34897388
DOI: 10.1242/dev.199401 -
Cellular and Molecular Gastroenterology... 2020
Topics: Diploidy; Gene Expression Profiling; Hepatocytes; Humans; Ploidies; Polyploidy; Stem Cells; Transcriptome
PubMed: 31654613
DOI: 10.1016/j.jcmgh.2019.09.008 -
Transgenic Research Aug 2021Plant breeding aims to develop improved crop varieties. Many crops have a polyploid and often highly heterozygous genome, which may make breeding of polyploid crops a... (Review)
Review
Plant breeding aims to develop improved crop varieties. Many crops have a polyploid and often highly heterozygous genome, which may make breeding of polyploid crops a real challenge. The efficiency of traditional breeding based on crossing and selection has been improved by using marker-assisted selection (MAS), and MAS is also being applied in polyploid crops, which helps e.g. for introgression breeding. However, methods such as random mutation breeding are difficult to apply in polyploid crops because there are multiple homoeologous copies (alleles) of each gene. Genome editing technology has revolutionized mutagenesis as it enables precisely selecting targets. The genome editing tool CRISPR/Cas is especially valuable for targeted mutagenesis in polyploids, as all alleles and/or copies of a gene can be targeted at once. Even multiple genes, each with multiple alleles, may be targeted simultaneously. In addition to targeted mutagenesis, targeted replacement of undesirable alleles by desired ones may become a promising application of genome editing for the improvement of polyploid crops, in the near future. Several examples of the application of genome editing for targeted mutagenesis are described here for a range of polyploid crops, and achievements and bottlenecks are highlighted.
Topics: CRISPR-Cas Systems; Crops, Agricultural; Gene Editing; Genome, Plant; Plant Breeding; Plants, Genetically Modified; Polyploidy
PubMed: 33846956
DOI: 10.1007/s11248-021-00251-0 -
Biology Letters Dec 2022Whole-genome duplication is a common mutation in eukaryotes with far-reaching phenotypic effects, the resulting morphological and fitness consequences and how they... (Meta-Analysis)
Meta-Analysis
Whole-genome duplication is a common mutation in eukaryotes with far-reaching phenotypic effects, the resulting morphological and fitness consequences and how they affect the survival of polyploid lineages are intensively studied. Another important factor may also determine the probability of establishment and success of polyploid lineages: inbreeding depression. Inbreeding depression is expected to play an important role in the establishment of neopolyploid lineages, their capacity to colonize new environments, and in the simultaneous evolution of ploidy and other life-history traits such as self-fertilization. Both theoretically and empirically, there is no consensus on the consequences of polyploidy on inbreeding depression. In this meta-analysis, we investigated the effect of polyploidy on the evolution of inbreeding depression, by performing a meta-analysis within angiosperm species. The main results of our study are that the consequences of polyploidy on inbreeding depression are complex and depend on the time since polyploidization. We found that young polyploid lineages have a much lower amount of inbreeding depression than their diploid relatives and their established counterparts. Natural polyploid lineages are intermediate and have a higher amount of inbreeding depression than synthetic neopolyploids, and a smaller amount than diploids, suggesting that the negative effect of polyploidy on inbreeding depression decreases with time since polyploidization.
Topics: Inbreeding Depression; Polyploidy; Diploidy; Inbreeding; Magnoliopsida
PubMed: 36514955
DOI: 10.1098/rsbl.2022.0477 -
Clinical and Translational Medicine Feb 2024Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA... (Review)
Review
Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs.
Topics: Animals; Mice; Cell Line, Tumor; Giant Cells; Antineoplastic Agents; Polyploidy; Neoplasms
PubMed: 38362620
DOI: 10.1002/ctm2.1567 -
Genes Jan 2024Cells with an abnormal number of chromosomes have been found in more than 90% of solid tumors, and among these, polyploidy accounts for about 40%. Polyploidized cells... (Review)
Review
Cells with an abnormal number of chromosomes have been found in more than 90% of solid tumors, and among these, polyploidy accounts for about 40%. Polyploidized cells most often have duplicate centrosomes as well as genomes, and thus their mitosis tends to promote merotelic spindle attachments and chromosomal instability, which produces a variety of aneuploid daughter cells. Polyploid cells have been found highly resistant to various stress and anticancer therapies, such as radiation and mitogenic inhibitors. In other words, common cancer therapies kill proliferative diploid cells, which make up the majority of cancer tissues, while polyploid cells, which lurk in smaller numbers, may survive. The surviving polyploid cells, prompted by acute environmental changes, begin to mitose with chromosomal instability, leading to an explosion of genetic heterogeneity and a concomitant cell competition and adaptive evolution. The result is a recurrence of the cancer during which the tenacious cells that survived treatment express malignant traits. Although the presence of polyploid cells in cancer tissues has been observed for more than 150 years, the function and exact role of these cells in cancer progression has remained elusive. For this reason, there is currently no effective therapeutic treatment directed against polyploid cells. This is due in part to the lack of suitable experimental models, but recently several models have become available to study polyploid cells in vivo. We propose that the experimental models in , for which genetic techniques are highly developed, could be very useful in deciphering mechanisms of polyploidy and its role in cancer progression.
Topics: Animals; Drosophila; Neoplasms; Polyploidy; Centrosome; Chromosomal Instability
PubMed: 38254985
DOI: 10.3390/genes15010096 -
Seminars in Cancer Biology Jun 2022Therapeutic resistance represents a major cause of death for most lethal cancers. However, the underlying mechanisms of such resistance have remained unclear. The... (Review)
Review
Therapeutic resistance represents a major cause of death for most lethal cancers. However, the underlying mechanisms of such resistance have remained unclear. The polyploid cells are due to an increase in DNA content, commonly associated with cell enlargement. In human, they play a variety of roles in physiology and pathologic conditions and perform the specialized functions during development, inflammation, and cancer. Recent work shows that cancer cells can be induced into polyploid giant cancer cells (PGCCs) that leads to reprogramming of surviving cancer cells to acquire resistance. In this article, we will review the polyploidy involved in development and inflammation, and the process of PGCCs formation and propagation that benefits to cell survival. We will discuss the potential opportunities in fighting resistant cancers. The increased knowledge of PGCCs will offer a completely new paradigm to explore the therapeutic intervention for lethal cancers.
Topics: Giant Cells; Humans; Inflammation; Neoplasms; Polyploidy
PubMed: 33839294
DOI: 10.1016/j.semcancer.2021.04.005 -
Development (Cambridge, England) Jun 2023The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in...
The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in nature but its regulators and significance in the placenta are unknown. We have discovered that many murine placental cell types are polyploid and have identified factors that license polyploidy using single-cell RNA sequencing. Myc is a key regulator of polyploidy and placental development, and is required for multiple rounds of DNA replication, likely via endocycles, in trophoblast giant cells. Furthermore, MYC supports the expression of DNA replication and nucleotide biosynthesis genes along with ribosomal RNA. Increased DNA damage and senescence occur in trophoblast giant cells without Myc, accompanied by senescence in the neighboring maternal decidua. These data reveal Myc is essential for polyploidy to support normal placental development, thereby preventing premature senescence. Our study, combined with available literature, suggests that Myc is an evolutionarily conserved regulator of polyploidy.
Topics: Animals; Female; Mice; Pregnancy; Placenta; Placentation; Polyploidy; Trophoblasts
PubMed: 37278344
DOI: 10.1242/dev.201581 -
The Plant Journal : For Cell and... Aug 2022Polyploidy is a major force shaping eukaryote evolution but poses challenges for meiotic chromosome segregation. As a result, first-generation polyploids often suffer...
Polyploidy is a major force shaping eukaryote evolution but poses challenges for meiotic chromosome segregation. As a result, first-generation polyploids often suffer from more meiotic errors and lower fertility than established wild polyploid populations. How established polyploids adapt their meiotic behaviour to ensure genome stability and accurate chromosome segregation remains an active research question. We present here a cytological description of meiosis in the model allopolyploid species Arabidopsis suecica (2n = 4x = 26). In large part meiosis in A. suecica is diploid-like, with normal synaptic progression and no evidence of synaptic partner exchanges. Some abnormalities were seen at low frequency, including univalents at metaphase I, anaphase bridges and aneuploidy at metaphase II; however, we saw no evidence of crossover formation occurring between non-homologous chromosomes. The crossover number in A. suecica is similar to the combined number reported from its diploid parents Arabidopsis thaliana (2n = 2x = 10) and Arabidopsis arenosa (2n = 2x = 16), with an average of approximately 1.75 crossovers per chromosome pair. This contrasts with naturally evolved autotetraploid A. arenosa, where accurate chromosome segregation is achieved by restricting crossovers to approximately 1 per chromosome pair. Although an autotetraploid donor is hypothesized to have contributed the A. arenosa subgenome to A. suecica, A. suecica harbours diploid A. arenosa variants of key meiotic genes. These multiple lines of evidence suggest that meiosis in the recently evolved allopolyploid A. suecica is essentially diploid like, with meiotic adaptation following a very different trajectory to that described for autotetraploid A. arenosa.
Topics: Arabidopsis; Diploidy; Genome, Plant; Meiosis; Polyploidy
PubMed: 35759495
DOI: 10.1111/tpj.15879