-
The Plant Cell Jul 2022Bread wheat (Triticum aestivum, genome BBAADD) is a young hexaploid species formed only 8,500-9,000 years ago through hybridization between a domesticated...
Bread wheat (Triticum aestivum, genome BBAADD) is a young hexaploid species formed only 8,500-9,000 years ago through hybridization between a domesticated free-threshing tetraploid progenitor, genome BBAA, and Aegilops tauschii, the diploid donor of the D subgenome. Very soon after its formation, it spread globally from its cradle in the fertile crescent into new habitats and climates, to become a staple food of humanity. This extraordinary global expansion was probably enabled by allopolyploidy that accelerated genetic novelty through the acquisition of new traits, new intergenomic interactions, and buffering of mutations, and by the attractiveness of bread wheat's large, tasty, and nutritious grain with high baking quality. New genome sequences suggest that the elusive donor of the B subgenome is a distinct (unknown or extinct) species rather than a mosaic genome. We discuss the origin of the diploid and tetraploid progenitors of bread wheat and the conflicting genetic and archaeological evidence on where it was formed and which species was its free-threshing tetraploid progenitor. Wheat experienced many environmental changes throughout its evolution, therefore, while it might adapt to current climatic changes, efforts are needed to better use and conserve the vast gene pool of wheat biodiversity on which our food security depends.
Topics: Bread; Diploidy; Evolution, Molecular; Genome, Plant; Hybridization, Genetic; Polyploidy; Tetraploidy; Triticum
PubMed: 35512194
DOI: 10.1093/plcell/koac130 -
Nature Apr 2022Diploid and stable karyotypes are associated with health and fitness in animals. By contrast, whole-genome duplications-doublings of the entire complement of...
Diploid and stable karyotypes are associated with health and fitness in animals. By contrast, whole-genome duplications-doublings of the entire complement of chromosomes-are linked to genetic instability and frequently found in human cancers. It has been established that whole-genome duplications fuel chromosome instability through abnormal mitosis; however, the immediate consequences of tetraploidy in the first interphase are not known. This is a key question because single whole-genome duplication events such as cytokinesis failure can promote tumorigenesis. Here we find that human cells undergo high rates of DNA damage during DNA replication in the first S phase following induction of tetraploidy. Using DNA combing and single-cell sequencing, we show that DNA replication dynamics is perturbed, generating under- and over-replicated regions. Mechanistically, we find that these defects result from a shortage of proteins during the G1/S transition, which impairs the fidelity of DNA replication. This work shows that within a single interphase, unscheduled tetraploid cells can acquire highly abnormal karyotypes. These findings provide an explanation for the genetic instability landscape that favours tumorigenesis after tetraploidization.
Topics: Chromosomal Instability; DNA Damage; DNA Replication; Gene Duplication; Humans; Karyotype; Mitosis; S Phase; Tetraploidy
PubMed: 35355016
DOI: 10.1038/s41586-022-04578-4 -
Oncotarget Nov 2014
Topics: Humans; Neoplasms; Tetraploidy
PubMed: 25526024
DOI: 10.18632/oncotarget.2790 -
Cancer Science Sep 2018Tetraploidy, a condition in which a cell has four homologous sets of chromosomes, is often seen as a natural physiological condition but is also frequently seen in... (Review)
Review
Tetraploidy, a condition in which a cell has four homologous sets of chromosomes, is often seen as a natural physiological condition but is also frequently seen in pathophysiological conditions such as cancer. Tetraploidy facilitates chromosomal instability (CIN), which is an elevated level of chromosomal loss and gain that can cause production of a wide variety of aneuploid cells that carry structural and numerical aberrations of chromosomes. The resultant genomic heterogeneity supposedly expedites karyotypic evolution that confers oncogenic potential in spite of the reduced cellular fitness caused by aneuploidy. Recent studies suggest that tetraploidy might also be associated with aging; mice with mutations in an intermediate filament protein have revealed that these tetraploidy-prone mice exhibit tissue disorders associated with aging. Cellular senescence and its accompanying senescence-associated secretory phenotype have now emerged as critical factors that link tetraploidy and tetraploidy-induced CIN with cancer, and possibly with aging. Here, we review recent findings about how tetraploidy is related to cancer and possibly to aging, and discuss underlying mechanisms of the relationship, as well as how we can exploit the properties of cells exhibiting tetraploidy-induced CIN to control these pathological conditions.
Topics: Aging; Animals; Cellular Senescence; Chromosomal Instability; Humans; Mice; Neoplasms; Tetraploidy
PubMed: 29949679
DOI: 10.1111/cas.13717 -
International Journal of Molecular... Apr 2017v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers,... (Review)
Review
v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers, and is critical in tumor progression through multiple processes. However, in some experimental conditions, v-Src causes growth suppression and apoptosis. In this review, we highlight recent progress in our understanding of cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src-expressing cells. v-Src induces cell cycle changes-such as the accumulation of the 4N cell population-and increases the number of binucleated cells, which is accompanied by an excess number of centrosomes. Time-lapse analysis of v-Src-expressing cells showed that cytokinesis failure is caused by cleavage furrow regression. Microscopic analysis revealed that v-Src induces delocalization of cytokinesis regulators including Aurora B and Mklp1. Tetraploid cell formation is one of the causes of chromosome instability; however, tetraploid cells can be eliminated at the tetraploidy checkpoint. Interestingly, v-Src weakens the tetraploidy checkpoint by inhibiting the nuclear exclusion of the transcription coactivator YAP, which is downstream of the Hippo pathway and its nuclear exclusion is critical in the tetraploidy checkpoint. We also discuss the relationship between v-Src-induced chromosome instability and growth suppression in v-Src-induced oncogenesis.
Topics: Animals; Cell Cycle Proteins; Cell Proliferation; Cell Transformation, Neoplastic; Chromosomal Instability; Cytokinesis; Genes, src; Genetic Variation; Humans; Mitosis; Protein Transport; Tetraploidy
PubMed: 28417908
DOI: 10.3390/ijms18040811 -
EMBO Reports Mar 2024Tumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells...
Tumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells by combining pH-dependent flow cytometry cell sorting from 3D colorectal tumor spheroids and transcriptomic profiling. Besides metabolic rewiring, we identify an increase in tetraploid cell frequency and DNA damage response as consistent hallmarks of acid-exposed cancer cells, supported by the activation of ATM and ATR signaling pathways. We find that regardless of the cell replication error status, both ATM and ATR inhibitors exert preferential growth inhibitory effects on acid-exposed cancer cells. The efficacy of a combination of these drugs with 5-FU is further documented in 3D spheroids as well as in patient-derived colorectal tumor organoids. These data position tumor acidosis as a revelator of the therapeutic potential of DNA repair blockers and as an attractive clinical biomarker to predict the response to a combination with chemotherapy.
Topics: Humans; Tetraploidy; Ataxia Telangiectasia Mutated Proteins; Signal Transduction; DNA Damage; DNA Repair; Protein Kinase Inhibitors; Colorectal Neoplasms
PubMed: 38366255
DOI: 10.1038/s44319-024-00089-7 -
Aging Oct 2017
Topics: Aging; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Humans; Mice; Mice, Transgenic; Neurons; Tetraploidy
PubMed: 29070731
DOI: 10.18632/aging.101312 -
BMC Plant Biology Nov 2023Artificial induction of polyploidy is the most common and effective way to improve the biological properties of Populus and develop new varieties of this tree. In this...
BACKGROUND
Artificial induction of polyploidy is the most common and effective way to improve the biological properties of Populus and develop new varieties of this tree. In this study, in order to confirm and expand earlier findings, we established a protocol using colchicine and based on an efficient shoot regeneration system of leaf blades to induce tetraploidy in vitro in three genotypes from diploid Populus hopeiensis. The stomatal characteristics, leaf blade size, and growth were evaluated for diploids and tetraploids of three genotypes.
RESULTS
We found that genotype, preculture duration, colchicine concentration, and colchicine exposure time had highly significant effects on the tetraploid induction rate. The optimal protocol for inducing tetraploidy in P. hopeiensis was to preculture leaf blades for 7 days and then treat them for 4 days with 40 mg/L colchicine. The tetraploid induction rates of genotypes BT1, BT3, and BT8 were 21.2, 11.4 and 16.7%, respectively. A total of 136 tetraploids were identified by flow cytometry analysis and somatic chromosome counting. The stomatal length, width, and density of leaf blades significantly differed between diploid and tetraploid plants. Compared with their diploid counterparts, the tetraploids produced larger leaf blades and had a slower growth rate. Our findings further document the modified morphological characteristics of P. hopeiensis following whole-genome duplication (e.g., induced tetraploidy).
CONCLUSIONS
We established a protocol for in vitro induction of tetraploidy from diploid leaf blades treated with colchicine, which can be applied to different genotypes of P. hopeiensis.
Topics: Tetraploidy; Populus; Polyploidy; Diploidy; Biological Variation, Population; Colchicine
PubMed: 37957587
DOI: 10.1186/s12870-023-04578-0 -
Scientific Reports May 2022One of the most important crops worldwide is wheat. Wheat domestication took place about 10,000 years ago. Not only that its wild progenitors have been discovered and...
One of the most important crops worldwide is wheat. Wheat domestication took place about 10,000 years ago. Not only that its wild progenitors have been discovered and phenotypically characterized, but their genomes were also sequenced and compared to modern wheat. While comparative genomics is essential to track genes that contribute to improvement in crop yield, comparative analyses of functional biological end-products, such as metabolites, are still lacking. With the advent of rigorous mass-spectrometry technologies, it is now possible to address that problem on a big-data scale. In attempt to reveal classes of metabolites, which are associated with wheat domestication, we analyzed the metabolomes of wheat kernel samples from various wheat lines. These wheat lines represented subspecies of tetraploid wheat along primary and secondary domestications, including wild emmer, domesticated emmer, landraces durum, and modern durum. We detected that the groups of plant metabolites such as plant-defense metabolites, antioxidants and plant hormones underwent significant changes during wheat domestication. Our data suggest that these metabolites may have contributed to the improvement in the agricultural fitness of wheat. Closer evaluation of specific metabolic pathways may result in the future in genetically-engineered high-yield crops.
Topics: Crops, Agricultural; Domestication; Metabolome; Tetraploidy; Triticum
PubMed: 35595776
DOI: 10.1038/s41598-022-11952-9 -
Cell Cycle (Georgetown, Tex.) 2015
Topics: Antineoplastic Agents; Chromosomal Instability; Drug Resistance, Multiple; Humans; Mitosis; Tetraploidy
PubMed: 26517196
DOI: 10.1080/15384101.2015.1084208