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At least 1,027 records · Page 57Linked to original sources
PubMed2005

Molecular characterization of a widespread, pathogenic, and antibiotic resistance-receptive Enterococcus faecalis lineage and dissemination of its putative pathogenicity island.

Enterococcus faecalis, a common cause of endocarditis and known for its capacity to transfer antibiotic resistance to other pathogens, has recently emerged as an important, multidrug-resistant nosocomial pathogen. However, knowledge of its lineages and the potential of particular clones of this species to disseminate and cause disease is limited. Using a nine-gene multilocus sequence typing (MLST) scheme, we identified an evolving and widespread clonal complex of E. faecalis that has caused outbreaks and life-threatening infections. Moreover, this unusual clonal complex was found to contain isolates of unexpected relatedness, including the first known U.S. vancomycin-resistant enterococcus (E. faecalis strain V583), the first known penicillinase-producing (Bla(+)) E. faecalis isolate, and the previously described widespread clone of penicillinase producers, a trait found in <0.1% of E. faecalis isolates. All members of this clonal cluster (designated as BVE for Bla(+) Van(r) endocarditis) were found to contain a previously described putative pathogenicity island (PAI). Further analysis of this PAI demonstrated its dissemination worldwide, albeit with considerable variability, confirmed its association with clinical isolates, and found a common insertion site in different clonal lineages. PAI deletions, MLST, and the uncommon resistances were used to predict the evolution of the BVE clonal cluster. The finding of a virulent and highly successful clonal complex of E. faecalis with different members resistant to the primary therapies of choice, ampicillin and vancomycin, has important implications for the evolution of virulence and successful lineages and for public health monitoring and control.

Bacterial Proteins↗
PubMed1997

Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome.

We describe the cytogenetic evolution of multiple cell lines in the gonadal tissue of a 10-year-old girl with mosaic Ullrich-Turner syndrome (UTS) involving clonal telomeric associations (tas) of the Y chromosome. G-band analysis of all tissues showed at least 2 cell lines; 45, X and 46,X,tas(Y;21)(q12;p13). However, analysis of left gonadal tissue of this patient showed the evolution of 2 additional cell lines, one designated 45,X,tas(Y;21)(q12;p13),-22 and the other 46,X,tas(Y;21)(q12;p13),+tas(Y;14)(q12;p13), -22. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei from uncultured gonadal tissue confirmed the findings of aneuploidy in the left gonadal tissue and extended the findings of aneuploidy to the tissue of the right gonad. The chromosome findings in the gonadal tissue of this patient suggest a preneoplastic karyotype relating to several distinct tumor associations. The clonal evolution of telomeric fusions indicates chromosomes instability and suggests the extra copy of the Y chromosome may have resulted from a fusion-related malsegregation. In addition, the extra Y suggests low-level amplification of a putative gonadoblastoma gene, while the loss of chromosome 22 suggests the loss of heterozygosity for genes on chromosome 22. This case demonstrates the utility of the study of gonadal tissue in 45,X/46XY UTS patients, and provides evidence that clonal telomeric fusions may, in rare cases, be associated with chromosome malsegregation and with the subsequent evolution of unstable karyotypes.

Child↗
PubMed2005

Predation effects on the evolution of life-history traits in a clonal oligochaete.

Although size at maturity and size and number of offspring are life-history traits widely studied in sexual and parthenogenetic reproduction, there is no such research on animals reproducing asexually without the involvement of gametes. Here we present an individual-based model in combination with experiments to study the clonal growth of Stylaria lacustris, an oligochaete reproducing through fission. We studied the effect of individual size at fission and fission ratio on clone fitness. Our results show that in benign environments without predators, fitness is higher when small worms produce small offspring. Then we included size-specific sublethal predation and found that the fitness of the clone is maximized when parental worms start fission at a large size and produce large descendants intercalated in the middle of the parental worm's body. These results agree with empirical findings. Furthermore, the results of our own laboratory experiment revealed that when S. lacustris is exposed to chemical alarm signals from injured conspecifics, it alters its life history in the same direction as predicted by the model. Our findings suggest that the effect of size-specific sublethal predation is similar to the effect of size-specific lethal predation because both modes of predation result in size-dependent prey mortality.

Animals↗
PubMed1995

Evolution of drug resistance in CCRF-CEM human leukemia cells selected by intermittent methotrexate exposure.

A clinically relevant mechanism of acquired methotrexate (MTX) resistance is decreased MTX polyglutamate (MTXGn) synthesis (McCloskey et al. J. Biol. Chem. 266:6181, 1991) secondary to deficient folylpolyglutamate synthetase (FPGS) activity. Earlier studies showed that this mechanism resulted after intermittent MTX treatment, but did not define its evolution in populations or its clonal frequency of occurrence and heterogeneity. We thus studied evolution of resistance in CCRF-CEM human leukemia cell populations and clones after repeated treatment with 30 microM MTX for 24 h. In populations, MTX resistance was detectable after 1 treatment and increased in degree as total cycles increased to 7. Defective MTXGn synthesis in populations was the only resistance mechanism detected, and FPGS activity in extracts decreased with treatment cycle. After 1 treatment, defective MTXGn synthesis was the major (27/48 clones) form of resistance; 18 clones were sensitive, while 1 clone with a DHFR-related change, no clones with decreased MTX uptake, and 2 complex phenotypes were observed. Sporadic clones with DHFR-mediated resistance appeared up to cycle 4, but defective MTXGn synthesis remained the major resistance mechanism. The degree of clonal resistance tended to increase with treatment cycle, but 1 clone in cycle 2 was similar to the clones from cycle 7. No change in FPGS gene copy number or restriction pattern, or FPGS mRNA level or size (2.3 Kb) was detected in populations. Decreased FPGS activity must result from decreased translation, increased protein turnover, or a point mutation affecting catalysis.

Antimetabolites, Antineoplastic↗
PubMed1995

Cytogenetic and flow cytometry DNA analysis of regional heterogeneity in a low grade human glioma.

This study combined flow cytometry with standard cytogenetic analysis of first division cells to evaluate regional heterogeneity in 38 spatially mapped regions of a low grade human oligoastrocytoma. Histologically, the tumor was relatively homogeneous. In contrast, flow cytometry and cytogenetic analyses identified variable percentages of near-diploid (ND; 35 to 57 chromosomes/metaphase) and near-tetraploid (81-103 chromosomes/metaphase) populations. The largest proportion of cells in the ND population was 46,XY with normal Giemsa bands; however, four karyotypically unrelated ND clones also were identified. The development of these clonal populations centered around a region in which more than 50% of the cells contained nonclonal abnormalities and which demonstrated more histological pleomorphism than any other region. The frequency of the nonclonal karyotypes suggested that this region was genetically unstable. Three of the clonal ND populations resided in small, spatially discreet areas of the tumor. The largest and the most widely distributed clonal population, 47,XY,+7, underwent further evolution to give rise to seven additional sidelines. This investigation demonstrates that low grade gliomas have areas of genetic instability capable of generating mutant cells with the capacity to proliferate and to form cellular foci. As a result, multiple, spatially distinct clonal populations can exist in low grade gliomas, some of which are capable of further cytogenetic evolution and clonal expansion, resulting in tumor progression.

Adult↗
PubMedDate not supplied

Clonal drift and role of chromosome dosage in human melanoma metastatic cell lines: a statistical analysis.

Karyotypic analyses were performed on twenty human melanoma clones and variants all deriving, following in vivo selections and/or in vitro cloning, from the parental M4Be cell line, but expressing different tumorigenicity (expressed as mean tumor weight) and metastatic ability (expressed as pulmonary metastasis frequency) after s.c. injection in antithymocyte immunosuppressed newborn rats. These cells were hypertriploid, showing quite comparable modal numbers (around 70). They all expressed a wide range of chromosome number per mitosis (28 to 198), as well as a large extent of karyotypic heterogeneity, showed by extensive clonal drifts within the different cell lines. Their common origin was ascertained by five clonal abnormal marker chromosomes deriving from chromosomes 6, 7, 8, 9, 11 and 14. Twenty-one additional marker chromosomes, most of them non clonal, were observed in the different cell lines. We developed a statistical analysis to search for putative relationship between the expression of tumorigenicity and metastatic ability and the evolution of specific subclones within the different cell lines. We showed that the expression of a high mean tumor weight and/or a high metastasis incidence was related to the modification of the ratio of different subclones within each cell line, and more especially to the emergence of subclones presenting partial losses of individual chromosomes or chromosomal fragments, which were encountered with a lower frequency in the low metastatic cell lines. The biological relevance of these findings in terms of clonal evolution and role of chromosome dosage in tumor progression is discussed.

Chromosome Aberrations↗
PubMed2004

Floral evolution and pollinator mate choice in a sexually deceptive orchid.

Sexually deceptive orchids mimic sex pheromones and appearance of female insects to attract males, which pollinate the flowers in an attempted mating. This study examines the effects of pollinator mate choice on orchid floral evolution using the Thynnine wasp Neozeleboria cryptoides (Smith) (Hymenoptera: Tiphiidae), which pollinates the sexually deceptive orchid Chiloglottis trapeziformis Fitzg. (i) When male wasps were given the choice between two female dummies of different sizes and identical amount of synthetic pheromone, they preferentially attempted to copulate with medium-sized dummies over small dummies. (ii) When given the choice between two dummies of identical size but different amounts of pheromone, males preferred the larger amount of pheromone. Larger amounts of pheromone generally attracted more males than smaller amounts. (iii) Orchid flower labella, which mimic a female body, were significantly longer and broader than female wasp bodies, and the flowers also produced on average 10 times more 'pheromone' than females. The evolution and maintenance of these exaggerated mating signals is likely to be mediated by the male pollinator behaviour demonstrated here. (iv) When five dummies were offered simultaneously in a 10 cm circular array, males rarely attempted copulation on more than one dummy during a single visit. This behaviour may foster the evolution or maintenance of clonality in C. trapeziformis, as it will minimize pollen exchange within clones.

Animals↗
PubMed2026

highSpaClone enables copy number alteration inference and tumor subclone analysis for high-resolution spatial transcriptomics.

High-resolution spatially resolved transcriptomics (SRT) offers unprecedented opportunities to investigate tumor heterogeneity but poses substantial computational and analytical challenges. Here, we present highSpaClone, a computational framework for copy number alteration (CNA) inference and tumor subclone identification from high-resolution SRT data across multiple spatial scales. By integrating spatial constraints into CNA estimation and clonal clustering, highSpaClone enables neighboring spatial locations to share information, thereby improving the robustness of genomic signals and the accuracy of subclone delineation. Across multiple Xenium and Visium HD datasets, highSpaClone revealed unique transcriptional programs, clonal evolutionary trajectories, and distinct tumor-microenvironment interactions. Furthermore, in human colorectal cancer samples, highSpaClone detected CNA events in histologically normal epithelial regions, highlighting early genomic alterations associated with field cancerization. These findings establish highSpaClone as a scalable framework for studying clonal architecture and tumor evolution.

CP: cancer biology↗
PubMed2006

Molecular evolution of porcine circovirus type 2 genomes: phylogeny and clonality.

Porcine circoviruses (PCVs) type 1 (PCV1) and type 2 (PCV2) show high levels of nucleotide similarity, but PCV1 is considered non-pathogenic and PCV2 has been associated with several disease outcomes in pigs, mainly postweaning multisystemic wasting syndrome (PMWS). After exploring different topologies of the origin of PCVs, it was concluded that PCV1 and PCV2 seem to have a common origin. On the other hand, PCV2 could be divided into two groups (1 and 2) and eight clusters (1A to 1C and 2A to 2E), but none of those was apparently associated with disease status or geographic area. When phylogenetic trees constructed with the whole PCV2 genome, the cap or the rep genes were compared, some incongruence was identified. The possible existence of recombination was evaluated and cluster 1B was found to have a possible recombinant origin. Selective pressure was detected in all parts of the PCV2 genome, especially in the rep gene. Finally, the cap gene was the more suitable phylogenetic and epidemiological marker for PCV2, despite the fact that the virus can undergo recombination mainly within the first part of the rep region.

Animals↗
PubMed2002

Experimental life-history evolution: selection on the allocation to sexual reproduction and its plasticity in a clonal plant.

Allocation to sexual reproduction is an important life-history trait in clonal plants. Different selection pressures between competitive and competition-free environments are likely to result in the evolution of specialized genotypes and to maintain genetic variation in reproductive allocation. Moreover, selection may also result in the evolution of plastic allocation strategies. The necessary prerequisite for evolution, heritable genetic variation, can best be studied with selection experiments. Starting from a base population of 102 replicated genotypes of the clonal herb Ranunculus reptans, we imposed selection on the proportion of flowering rosettes in the absence of competition (base population: mean = 0.391, broad-sense heritability = 0.307). We also selected on the plasticity in this trait in response to competition with a naturally coexisting grass in a parallel experiment (base population: 14% lower mean in the presence of competition, broad-sense heritability = 0.072). After two generations of bidirectional selection, the proportion of flowering rosettes was 26% higher in the high line than in the low line (realized heritability +/- SE = 0.205 +/- 0.017). Moreover, genotypes of the high line had 11% fewer carpels per flower, a 22% lower proportion of rooted rosettes, and a 39% smaller average distance between rosettes within a clone. In the second experiment, we found no significant responses to selection for high and low plasticity in the proportion of flowering rosettes (realized heritability +/- SE = -0.002 +/- 0.013). Our study indicates a high heritability and potential for further evolution of the proportion of flowering rosettes in R. reptans, but not for its plasticity, which may have been fixed by past evolution at its current level. Moreover, our results demonstrate strong genetic correlations between allocation to sexual reproduction and other clonal life-history characteristics.

Biological Evolution↗
PubMed2004

Evolution of the core genome of Pseudomonas syringae, a highly clonal, endemic plant pathogen.

Pseudomonas syringae is a common foliar bacterium responsible for many important plant diseases. We studied the population structure and dynamics of the core genome of P. syringae via multilocus sequencing typing (MLST) of 60 strains, representing 21 pathovars and 2 nonpathogens, isolated from a variety of plant hosts. Seven housekeeping genes, dispersed around the P. syringae genome, were sequenced to obtain 400 to 500 nucleotides per gene. Forty unique sequence types were identified, with most strains falling into one of four major clades. Phylogenetic and maximum-likelihood analyses revealed a remarkable degree of congruence among the seven genes, indicating a common evolutionary history for the seven loci. MLST and population genetic analyses also found a very low level of recombination. Overall, mutation was found to be approximately four times more likely than recombination to change any single nucleotide. A skyline plot was used to study the demographic history of P. syringae. The species was found to have maintained a constant population size over time. Strains were also found to remain genetically homogeneous over many years, and when isolated from sites as widespread as the United States and Japan. An analysis of molecular variance found that host association explains only a small proportion of the total genetic variation in the sample. These analyses reveal that with respect to the core genome, P. syringae is a highly clonal and stable species that is endemic within plant populations, yet the genetic variation seen in these genes only weakly predicts host association.

Base Sequence↗
PubMed1992

Evolution of B-cell lymphoma from pseudolymphoma. A multidisciplinary approach using histology, immunohistochemistry, and Southern blot analysis.

Cutaneous B-cell lymphomas are rare neoplasms that can present as lesions involving solely the skin or develop in association with a systemic lymphoma. Histologically they are often difficult to differentiate from pseudolymphomas, and the use of immunohistochemistry may be necessary to correctly classify them. We report a study of multiple skin lesions in a patient who initially presented with multiple pseudolymphomas, apparently associated with an immune response to the dye of his tattoos. Over a period of 4 years his skin lesions evolved from histologically benign and immunologically polyclonal pseudolymphomas to a histologically malignant and immunologically monoclonal B-cell large cell lymphoma. Genotypic analysis with a probe for the heavy-chain immunoglobulin gene demonstrated the presence of clonal B-cell populations in all of the pseudolymphoma biopsy samples as well as in the subsequent lymphoma tissue samples, with a pattern of clonal bands suggestive of evolution of the B-cell clones. These findings suggest that the development of B-cell lymphoma in this patient was related to a persistent abnormal immune response to the chronic antigenic stimulus of the dye of the tattoo. The presence of clonal B-cell populations in pseudolymphoma by Southern blot analysis may be useful in predicting those patients who will subsequently develop overt lymphoma.

Blotting, Southern↗
PubMed2006

The evolution of adaptive immune systems.

A clonally diverse anticipatory repertoire in which each lymphocyte bears a unique antigen receptor is the central feature of the adaptive immune system that evolved in our vertebrate ancestors. The survival advantage gained through adding this type of adaptive immune system to a pre-existing innate immune system led to the evolution of alternative ways for lymphocytes to generate diverse antigen receptors for use in recognizing and repelling pathogen invaders. All jawed vertebrates assemble their antigen-receptor genes through recombinatorial rearrangement of different immunoglobulin or T cell receptor gene segments. The surviving jawless vertebrates, lampreys and hagfish, instead solved the receptor diversification problem by the recombinatorial assembly of leucine-rich-repeat genetic modules to encode variable lymphocyte receptors. The convergent evolution of these remarkably different adaptive immune systems involved innovative genetic modification of innate-immune-system components.

Animals↗
PubMed1992

Sexuality in a natural population of bacteria--Bacillus subtilis challenges the clonal paradigm.

Reproduction by binary fission necessarily establishes a clonal genotypic structure in bacterial populations unless a high rate of genetic recombination opposes it. Several genetic properties were examined for a wild population of Bacillus subtilis in the Sonoran Desert of Arizona to assess the extent of recombination in a natural population. These properties included allozyme variation revealed by multilocus enzyme electrophoresis, phage and antibiotic resistance, and restriction fragment length polymorphism with Southern hybridization. Evidence of extensive genetic recombination was found along with evidence of modest clonal structure. Recombination must be frequent relative to binary fission in this population. This mixed population structure provides broader options for bacterial evolution than would a purely clonal structure.

Bacillus subtilis↗
PubMed2004

Analysis of the allelic diversity of the mycobacterial interspersed repetitive units in Mycobacterium tuberculosis strains of the Beijing family: practical implications and evolutionary considerations.

A study set comprised 44 Mycobacterium tuberculosis strains of the Beijing family selected for their representativeness among those previously characterized by IS6110-RFLP and spoligotyping (Northwest Russia, 1997 to 2003). In the present study, these strains were subjected to mycobacterial interspersed repetitive units (MIRU) typing to assess a discriminatory power of the 12-MIRU-loci scheme (P. Supply et al., J. Clin. Microbiol. 39:3563-3571, 2001). The 44 Russian Beijing strains were subdivided into 12 MIRU types with identical profiles: 10 unique strains and two major types shared by 10 and 24 strains. Thus, basically, two distinct sublineages appear to shape the evolution of the Beijing strains in Russia. Most of the MIRU loci were found to be (almost) monomorphic in the Russian Beijing strains; the Hunter-Gaston discriminatory index (HGDI) for all 12 loci taken together was 0.65, whereas MIRU26 (the most variable in our study) showed a moderate level of discrimination (0.49). The results were compared against all available published MIRU profiles of Beijing strains from Russia (3 strains) and other geographic areas (51 strains in total), including South Africa (38 strains), East Asia (7 strains), and the United States (4 strains). A UPGMA (unweighted pair-group method with arithmetic averages)-based tree was constructed. Interestingly, no MIRU types were shared by Russian and South African strains (the two largest samples in this analysis), whereas both major Russian types included also isolates from other locations (United States and/or East Asia). This implies the evolution of the Beijing genotype to be generally strictly clonal, although a possibility of a convergent evolution of the MIRU loci cannot be excluded. We propose a dissemination of the prevailing local Beijing clones to have started earlier in South Africa rather than in Russia since more monomorphic loci were identified in Russian samples than in South African samples (mean HGDI scores, 0.08 versus 0.17). To conclude, we suggest to use a limited number of MIRUs for preliminary subdivision of Beijing strains in Russian (loci 26 + 31), South African (10 + 26 + 39), and global settings (10 + 26 + 39).

Alleles↗
PubMed1996

T-cell receptor J beta 1/J beta 2 locus rearrangements in an HTLV-1-positive T-cell lymphoma with complex chromosomal aberrations.

We report a case of human T-cell lymphotropic virus type 1 (HTLV-1)-infected adult T-cell lymphoma that has multiple chromosomal abnormalities, including the presence of an additional 7q22-36, which contains the locus of the T-cell receptor (TCR) beta chain gene. Specific TCR J beta 1/J beta 2 gene rearrangements were detected in both marrow and peripheral blood DNA, with evidence of further evolution of the transformed clonal population within the peripheral lymphocytes. To our knowledge, this is the first case in which gene rearrangements have been associated with additional TCR loci. Consequently, it is advised that every effort should be made to correlate chromosomal abnormalities with gene rearrangement by molecular methods.

Adult↗