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Current Biology : CB Sep 2022Whole-genome duplication, leading to polyploidy and endopolyploidy, is widespread throughout the tree of life. Both polyploidy and endopolyploidy can increase cell size...
Whole-genome duplication, leading to polyploidy and endopolyploidy, is widespread throughout the tree of life. Both polyploidy and endopolyploidy can increase cell size via nucleotypic effects, but the phenotypic consequences of increased cell size at the tissue and whole-organism levels are less well understood. We quantified the consequences of autopolyploidy and endopolyploidy in nine diploid accessions of Arabidopsis thaliana, representing a gradient in endopolyploidy, to their corresponding experimentally synthesized neo-tetraploid and neo-octoploid cytotypes. The increase in cell size following genome duplication increased plant storage capacity, which increased tolerance of resource limitation, but also incurred biomechanical costs because of a reduction in the amount of cell wall per unit tissue volume. Our findings also show that the functional consequences of autopolyploidy can vary with accession identity, and the presence of this variation suggests that there is potential for adaptation following whole-genome duplication.
Topics: Arabidopsis; Diploidy; Genome, Plant; Humans; Polyploidy
PubMed: 35944542
DOI: 10.1016/j.cub.2022.07.019 -
Stem Cells and Development Dec 2019A major objective of modern biomedical research aims to promote tissue self-regeneration after injury, obviating the need for whole organ transplantation and avoiding... (Review)
Review
A major objective of modern biomedical research aims to promote tissue self-regeneration after injury, obviating the need for whole organ transplantation and avoiding mortality due to organ failure. Identifying the population of cells capable of regeneration, alongside understanding the molecular mechanisms that activate that population to re-enter the cell cycle, are two important steps to advancing the field of endogenous tissue regeneration toward the clinic. In recent years, an emerging trend has been observed, whereby polyploidy of relevant parenchymal cells, arising from alternative cell cycles as part of a normal developmental process, is linked to restricted proliferative capacity of those cells. An accompanying hypothesis, therefore, is that a residual subpopulation of diploid parenchymal cells retains proliferative competence and is the major driver for any detected postnatal cell turnover. In this perspective review, we examine the emerging literature on residual diploid parenchymal cells and the possible link of this population to endogenous tissue regeneration, in the context of both heart and liver. We speculate on additional cell types that may play a similar role in their respective tissues and discuss outstanding questions for the field.
Topics: Diploidy; Heart; Humans; Liver; Polyploidy; Regeneration; Tissue Engineering
PubMed: 31608782
DOI: 10.1089/scd.2019.0193 -
Vaccine Aug 2022Shorter rabies pre-exposure prophylaxis (PrEP) regimens may offer improved convenience and feasibility over classic 3-week regimens, for example in regions with poor... (Randomized Controlled Trial)
Randomized Controlled Trial
One-week intramuscular or intradermal pre-exposure prophylaxis with human diploid cell vaccine or Vero cell rabies vaccine, followed by simulated post-exposure prophylaxis at one year: A phase III, open-label, randomized, controlled trial to assess immunogenicity and safety.
Shorter rabies pre-exposure prophylaxis (PrEP) regimens may offer improved convenience and feasibility over classic 3-week regimens, for example in regions with poor access to vaccines or for travelers to rabies-endemic regions. In this multicenter, open-label, controlled trial, 570 healthy participants aged 2-64 years were randomized to receive: 1-week PrEP (vaccination days [D]0 and 7; Group 1) or classic 3-week PrEP regimen (D0, D7, and D21; Group 2) with one 1.0 mL intramuscular [IM] dose of human diploid cell culture rabies vaccine (HDCV) at each visit; 1-week PrEP with two 0.1 mL intradermal (ID) HDCV doses at each visit (Group 3); or 1-week PrEP with one 0.5 mL IM dose (Group 4) or two 0.1 mL ID doses (Group 5) of Vero cell rabies vaccine (PVRV) at each visit. Participants received simulated post-exposure prophylactic (PEP) vaccination (two IM or ID doses of HDCV or PVRV three days apart) one year later. Rabies virus neutralizing antibody titers and seroconversion (titers ≥ 0.5 IU/mL) rates were assessed 14 days and up to 1 year post-PrEP, and pre- and post-PEP. Safety was assessed throughout the study. Seroconversion rates were high 14 days post-last PrEP injection (ranging from 96.7 % to 97.2 % across groups 1, 3-5; 1-week PrEP) and reached 100 % in Group 2 (3-week PrEP). Non-inferiority of Group 1 versus Group 2 in terms of seroconversion rates 14 days post-last PrEP injection (primary objective) was not demonstrated. After simulated PEP, all groups showed rapid and robust immune responses, with all but one participant achieving seroconversion (titers ≥ 0.5 IU/mL). There were no safety concerns, and the tolerability profiles of the vaccines were similar across the groups. A 1-week, IM or ID PrEP regimen with HDCV or PVRV provided efficacious priming, enabling rapid robust anamnestic responses to simulated PEP 1 year later across age groups. ClinicalTrials.gov number: NCT03700242. WHO Universal Trial Number (UTN): U1111-1183-5743.
Topics: Animals; Antibodies, Viral; Chlorocebus aethiops; Diploidy; Humans; Injections, Intradermal; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Rabies; Rabies Vaccines; Rabies virus; Vaccination; Vero Cells
PubMed: 35933278
DOI: 10.1016/j.vaccine.2022.07.037 -
Methods in Molecular Biology (Clifton,... 2023Analyzing autopolyploid genetic data still presents numerous challenges due to, e.g., missing dosage information of genotypes and the presence of multiple ploidy levels...
Analyzing autopolyploid genetic data still presents numerous challenges due to, e.g., missing dosage information of genotypes and the presence of multiple ploidy levels within species or populations, but also because the choice of software is limited when compared to what is available for diploid data. However, over the last years, the number of software programs that can deal with polyploid data is slowly increasing. The software GENODIVE is one of the most widely used programs for the analysis of polyploid genetic data, presenting a wide array of different methods. In this chapter, I outline several frequently used types of population genetic analyses and explain how these apply to polyploid data, including possible pitfalls and biases. I then explain how GENODIVE approaches these analyses and whether and how it can overcome possible biases. Specifically, I focus on analyses of genetic diversity, Hardy-Weinberg equilibrium, quantifying population differentiation, clustering, and calculation of genetic distances. GENODIVE can be downloaded freely from http://www.patrickmeirmans.com/software .
Topics: Humans; Cluster Analysis; Diploidy; Genotype; Ploidies; Polyploidy
PubMed: 36720818
DOI: 10.1007/978-1-0716-2561-3_14 -
Stem Cell Reports May 2023Humans are diploid organisms, and triploidy in human embryos is responsible for ∼10% of spontaneous miscarriages. Surprisingly, some pregnancies proceed to triploid...
Humans are diploid organisms, and triploidy in human embryos is responsible for ∼10% of spontaneous miscarriages. Surprisingly, some pregnancies proceed to triploid newborns that suffer from many neuro-developmental disorders. To investigate the impact of triploidy on human development, we generate triploid human embryonic stem cells (hESCs) by fusing isogenic haploid and diploid hESCs. Comparison of the transcriptome, methylome, and genome-wide replication timing shows general similarity between diploid and triploid hESCs. However, triploid cells have a larger volume than diploid cells, demonstrating decreased surface-area-to-volume ratio. This leads to a significant downregulation of cell surface ion channel genes, which are more essential in neural progenitors than in undifferentiated cells, leading to inhibition of differentiation, and it affects the neuronal differentiation ability of triploid hESCs, both in vitro and in vivo. Notably, our research establishes a platform to study triploidy in humans and points to their pathology as observed in triploid embryos.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Triploidy; Human Embryonic Stem Cells; Cell Differentiation; Genome; Genomics; Diploidy
PubMed: 37116485
DOI: 10.1016/j.stemcr.2023.04.001 -
BMC Genomics Oct 2020In diploid cells, it is important to construct maternal and paternal Hi-C contact maps respectively since the two homologous chromosomes can differ in chromatin...
BACKGROUND
In diploid cells, it is important to construct maternal and paternal Hi-C contact maps respectively since the two homologous chromosomes can differ in chromatin three-dimensional (3D) organization. Though previous softwares could construct diploid (maternal and paternal) Hi-C contact maps by using phased genetic variants, they all neglected the systematic biases in diploid Hi-C contact maps caused by variable genetic variant density in the genome. In addition, few of softwares provided quantitative analyses on allele-specific chromatin 3D organization, including compartment, topological domain and chromatin loop.
RESULTS
In this work, we revealed the feature of allele-assignment bias caused by the variable genetic variant density, and then proposed a novel strategy to correct the systematic biases in diploid Hi-C contact maps. Based on the bias correction, we developed an integrated tool, called HiCHap, to perform read mapping, contact map construction, whole-genome identification of compartments, topological domains and chromatin loops, and allele-specific testing for diploid Hi-C data. Our results show that the correction on allele-assignment bias in HiCHap does significantly improve the quality of diploid Hi-C contact maps, which subsequently facilitates the whole-genome identification of diploid chromatin 3D organization, including compartments, topological domains and chromatin loops. Finally, HiCHap also supports the data analysis for haploid Hi-C maps without distinguishing two homologous chromosomes.
CONCLUSIONS
We provided an integrated package HiCHap to perform the data processing, bias correction and structural analysis for diploid Hi-C data. The source code and tutorial of software HiCHap are freely available at https://pypi.org/project/HiCHap/ .
Topics: Chromatin; Chromosomes; Data Analysis; Diploidy; Software
PubMed: 33109075
DOI: 10.1186/s12864-020-07165-x -
American Journal of Botany Jul 2023Recently formed allopolyploids Tragopogon mirus and T. miscellus and their diploid parental species, T. dubius, T. porrifolius, and T. pratensis, offer a rare...
PREMISE
Recently formed allopolyploids Tragopogon mirus and T. miscellus and their diploid parental species, T. dubius, T. porrifolius, and T. pratensis, offer a rare opportunity to study the earliest stages of allopolyploidy. The allopolyploid species have also been resynthesized, allowing comparisons between the youngest possible allopolyploid lineages and their natural, established counterparts. For the first time, we compared phenotypic traits on a large scale in Tragopogon diploids, natural allopolyploids, and three generations of synthetic allopolyploids.
METHODS
Our large common-garden experiment measured traits in growth, development, physiology, and reproductive fitness. We analyzed trait differences between allopolyploids and their parental species, and between synthetic and natural allopolyploids.
RESULTS
As in many polyploids, the allopolyploid species had some larger physical traits and a higher capacity for photosynthesis than diploid species. Reproductive fitness traits were variable and inconsistent. Allopolyploids had intermediate phenotypes compared to their diploid parents in several traits, but patterns of variation often varied between allopolyploid complexes. Resynthesized and natural allopolyploid lines generally showed minor to nonexistent trait differences.
CONCLUSIONS
In Tragopogon, allopolyploidy results in some typical phenotypic changes, including gigas effects and increased photosynthetic capacity. Being polyploid did not produce a significant reproductive advantage. Comparisons between natural and synthetic T. mirus and T. miscellus are consistent with very limited, idiosyncratic phenotypic evolution following allopolyploidization.
Topics: Tragopogon; Diploidy; Polyploidy; North America; Genome, Plant
PubMed: 37210744
DOI: 10.1002/ajb2.16189 -
MBio Aug 2022species are obligate fungal biotrophs that colonize the lungs of mammals. They cause deadly pneumonia in immunocompromised hosts. The sexual phase seems obligate during...
species are obligate fungal biotrophs that colonize the lungs of mammals. They cause deadly pneumonia in immunocompromised hosts. The sexual phase seems obligate during their life cycle and essential for survival because it is believed to ensure proliferation and transmission between hosts. Here, we consider if the sexual phase is initiated by the fusion of two cells or by nucleus duplication in order to generate diploid cells that can undergo meiosis. The juxtaposition of the nucleus-associated organelles of pairs of cells with fused cytoplasmic membranes demonstrated that cell fusion can occur. Nevertheless, the frequency of cell fusion remains to be determined, and it cannot be excluded that both cell fusion and nucleus duplication are used to ensure the occurrence of the essential sexual phase. culturing of these fungi is a major milestone that could clarify the issue.
Topics: Animals; Cell Fusion; Diploidy; Mammals; Meiosis; Pneumocystis; Reproduction
PubMed: 35726921
DOI: 10.1128/mbio.00859-22 -
Cell Research Nov 2015To maintain homeostasis, organs replace cells lost through normal cellular turnover, often through the straightforward replication of existing cells. A recent paper in...
To maintain homeostasis, organs replace cells lost through normal cellular turnover, often through the straightforward replication of existing cells. A recent paper in Nature shows that cells in the liver are not equivalent when it comes to their replicative capacity; rather, a subset of hepatocytes defined by the maintenance of active Wnt signaling bears the brunt of responsibility for maintaining liver mass.
Topics: Animals; Axin Protein; Diploidy; Female; Hepatocytes; Homeostasis; Liver; Male
PubMed: 26403190
DOI: 10.1038/cr.2015.117 -
Genome Biology and Evolution May 2022Many animal species are haplodiploid: their fertilized eggs develop into diploid females and their unfertilized eggs develop into haploid males. The unique genetic...
Many animal species are haplodiploid: their fertilized eggs develop into diploid females and their unfertilized eggs develop into haploid males. The unique genetic features of haplodiploidy raise the prospect that these systems can be used to disentangle the population genetic consequences of haploid and diploid selection. To this end, sex-specific reproductive genes are of particular interest because, while they are shared within the same genome, they consistently experience selection in different ploidal environments. However, other features of these genes, including sex-specific expression and putative involvement in postcopulatory sexual selection, are potentially confounding factors because they may also impact the efficacy of selection asymmetrically between the sexes. Thus, to properly interpret evolutionary genomic patterns, it is necessary to generate a null expectation for the relative amount of polymorphism and divergence we expect to observe among sex-specific genes in haplodiploid species, given differences in ploidal environment, sex-limited expression, and their potential role in sexual selection. Here, we derive the theoretical expectation for the rate of evolution of sex-specific genes in haplodiploid species, under the assumption that they experience the same selective environment as genes expressed in both sexes. We find that the null expectation is that reproductive genes evolve more rapidly than constitutively expressed genes in haplodiploid genomes. However, despite the aforementioned differences, the null expectation does not differ between male- and female-specific reproductive genes, when assuming additivity. Our theoretical results provide an important baseline expectation that should be used in molecular evolution studies comparing rates of evolution among classes of genes in haplodiploid species.
Topics: Animals; Diploidy; Female; Genetics, Population; Genome; Haploidy; Male; Reproduction
PubMed: 35640985
DOI: 10.1093/gbe/evac070