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PubMed2002

The evolution and maintenance of monoecy and dioecy in Sagittaria latifolia (Alismataceae).

Plant species rarely exhibit both monoecious and dioecious sexual systems. This limits opportunities to investigate the consequences of combined versus separate sex function on mating patterns and genetic variation and the analysis of factors responsible for the evolution and maintenance of the two sexual systems. Populations of the North American clonal aquatic Sagittaria latifolia are usually either monoecious or dioecious and often grow in close geographic proximity. We investigated mating patterns, genetic structure, and relationships between the two sexual systems using allozyme variation in populations from southern Ontario, Canada. As predicted, selfing rates in monoecious populations (n = 6, mean = 0.41) were significantly higher than in dioecious populations (n = 6, mean = 0.11). Moreover, marker-based estimates of inbreeding depression (delta) indicated strong selection against inbred offspring in both monoecious (mean delta = 0.83) and dioecious (mean delta = 0.84) populations. However, the difference in selfing rate between the sexual systems was not reflected in contrasting levels of genetic variation. Our surveys of 12 loci in 15 monoecious and 11 dioecious populations revealed no significant differences in the proportion of polymorphic loci (P), number of alleles per locus (A), or observed and expected heterozygosity (H(o) and H(e), respectively). Strong inbreeding depression favoring survival of outcrossed offspring may act to maintain similar levels of diversity between monoecious and dioecious populations. Despite geographical overlap between the two sexual systems in southern Ontario, a dendrogram of genetic relationships indicated two distinct clusters of populations largely corresponding to monoecious and dioecious populations. Reproductive isolation between monoecious and dioecious populations appears to be governed, in part, by observed differences in habitat and life history. We suggest that selfing and inbreeding depression in monoecious populations are important in the transition from monoecy to dioecy and that the maintenance of distinct sexual systems in S. latifolia is governed by interactions between ecology, life history, and mating.

Biological Evolution↗
PubMed1996

Clinical aspects, cytogenetics and disease evolution in myelodysplastic syndromes.

Myelodysplastic syndrome (MDS) is a morphologically characterized hematologic entity that is one of the clonal myeloproliferative disorders. Approximately 50 approximately 70% of MDS patients have cytogenetic abnormalities; these are usually chromosomal deletions, but some involve translocations such as t(1;7) (q10;p10). Translocations involving chromosomal regions 3q26 or 22q11 are often therapy-related. Recent studies have demonstrated that cytogenetic changes in MDS patients have clinical relevance. Accordingly, there are now scoring systems for predicting the prognoses of MDS patients. In this review, we describe the clinical significance of cytogenetic changes in MDS. We include MDS with some atypical forms, such as MDS with hypocellular bone marrow, MDS with minimal dysplasia, and MDS with myelofibrosis.

Chromosomes, Human↗
PubMed1987

Spontaneous in vitro evolution of lytic specificity of cytotoxic T lymphocyte clones isolated from murine intestinal epithelium.

Three long-term clonally derived cytotoxic lines have been established from isolates of murine intraepithelial lymphocytes (IEL). All three lines were selected for with antigen and represent two allospecific cytotoxic T lymphocyte (CTL) clones and a major histocompatibility complex (MHC)-restricted clone specific for a murine minor histocompatibility antigen. On long-term in vitro culture, IEL clones gradually lost antigen-specific lytic activity and simultaneously acquired the capacity to lyse natural killer (NK)-sensitive target cells which, in some cases, required high-level lymphokine activation. Of interest was the finding that, despite changes in lytic specificity, IEL clones remained strictly antigen-dependent for proliferation. A murine CTL clone of splenic origin, which was propagated under culture conditions identical to those used for IEL, did not exhibit changes in lytic specificity, suggesting that acquired changes in IEL function cannot be attributed solely to the influence of in vitro culture. Phenotypic analyses of IEL clones with altered lytic specificity revealed that all lines remained Thy-1+, Lyt-2+, L3T4-, with or without lytic activation by lymphokines. The expression of CT-1, a murine CTL activation antigen, and asialo GM1, a murine NK cell marker, were variable on IEL clones, and their presence did not correlate with the changes in lytic behavior. Collectively, these findings provide evidence, at the clonal level, that at least some NK activity present in isolates of murine IEL may originate from antigen-specific CTL. The data also indicate that, on binding antigen, different signals are conveyed to T cells, resulting in proliferation or target cell lysis.

Animals↗
PubMed1987

Rapid evolution of RNA viruses.

The high error rate inherent in all RNA synthesis provides RNA virus genomes with extremely high mutation rates. Thus nearly all large RNA virus clonal populations are quasispecies collections of differing, related genomes (14, 49). These rapidly mutating populations can remain remarkably stable under certain conditions of replication. Under other conditions, virus-population equilibria become disturbed, and extremely rapid evolution can result. This extreme variability and rapid evolution can cause severe problems with previously unknown virus diseases (such as AIDS). It also presents daunting challenges for the design of effective vaccines for the control of diseases caused by rapidly evolving RNA virus populations.

Acute Disease↗
PubMed1984

Chromosome studies in polycythemia vera patients.

One hundred thirty-five polycythemia vera (PV) patients (30 untreated by chemotherapy and 105 treated) were studied cytogenetically . The incidence of clonal chromosomal abnormalities was 20.7% (28 patients in nonleukemic phase). The incidence of 20q - was 3.7% (5 patients). The presence of cytogenetically abnormal clones did not allow prediction of the evolution of the disease. In a few cases, abnormal clones disappeared at the time of later studies. Although nonrandom, the majority of clonal chromosomal abnormalities are believed to be secondary events in PV patients.

Aged↗
PubMed1999

Effect of retreatment with interferon alone or interferon plus ribavirin on hepatitis C virus quasispecies diversification in nonresponder patients with chronic hepatitis C.

Alpha interferon (IFN-alpha) treatment is effective on a long-term basis in only 15 to 25% of patients with chronic hepatitis C. The results of recent trials indicate that response rates can be significantly increased when IFN-alpha is given in combination with ribavirin. However, a large number of patients do not respond even to combination therapy. Nonresponsiveness to IFN is characterized by evolution of the hepatitis C virus (HCV) quasispecies. Little is known about the changes occurring within the HCV genomes when nonresponder patients are retreated with IFN or with IFN plus ribavirin. In the present study we have examined the genetic divergence of HCV quasispecies during unsuccessful retreatment with IFN or IFN plus ribavirin. Fifteen nonresponder patients with HCV-1 (4 patients with HCV-1a and 11 patients with HCV-1b) infection were studied while being retreated for 2 months (phase 1) with IFN-alpha (6 MU given three times a week), followed by IFN plus ribavirin or IFN alone for an additional 6 months (phase 2). HCV quasispecies diversification in the E2 hypervariable region-1 (HVR1) and in the putative NS5A IFN sensitivity determining region (ISDR) were analyzed for phase 1 and phase 2 by using the heteroduplex tracking assay and clonal frequency analysis techniques. A major finding of this study was the relatively rapid evolution of the HCV quasispecies observed in both treatment groups during the early phase 1 compared to the late phase 2 of treatment. The rate of quasispecies diversification in HVR1 was significantly higher during phase 1 versus phase 2 both in patients who received IFN plus ribavirin (P = 0.017) and in patients who received IFN alone (P = 0. 05). A trend toward higher rates of quasispecies evolution in the ISDR was also observed during phase 1 in both groups, although the results did not reach statistical significance. However, the NS5A quasispecies appeared to be rather homogeneous and stable in most nonresponder patients, suggesting the presence of a single well-fit major variant, resistant to antiviral treatment, in agreement with published data which have identified an IFN sensitivity determinant region within the NS5A. During the entire 8 months of retreatment, there was no difference in the rate of fixation of mutation between patients who received combination therapy and patients who were treated with IFN alone, suggesting that ribavirin had no major effects on the evolution of the HCV quasispecies after the initial 2 months of IFN therapy.

Adult↗
PubMed1995

The nature of gene evolution on the mammalian Y chromosome: lessons from Sry.

With the exception of a small region, heteromorphic sex chromosomes of mammals do not undergo recombination in male meiosis. As a result, the majority of the Y chromosome is clonally transmitted through paternal lineages. Numerous phenomena, including the Hill-Robertson effect, Muller's ratchet, genetic hitch-hiking, and male-driven molecular evolution, are associated with the special transmission properties of the Y chromosome, and can potentially explain the tempo and pattern of gene evolution on the mammalian Y. We explore these phenomena in light of comparative data from the Y-linked sex-determining locus, Sry. Sry exhibits rapid amino acid divergence between species and little to no variation within species. We find no evidence for directional selection acting on this locus. The pattern of evolution between species is consistent with the Hill-Robertson effect and Muller's ratchet. Lack of variation in Sry within species may reflect genetic hitch-hiking, however, we cannot exclude the confounding effects of small effective population size of Y chromosomes. We find no support for male-driven molecular evolution for Sry in Old World mice and rats. However, a more appropriate test of this hypothesis would be to compare the evolution of Sry to the X-linked Sox3 gene in these same species. Clearly, more comparative studies of Sry and other Y-linked loci are needed to characterize the effects of Y chromosome transmission on the evolution of Y-linked sequences.

Animals↗
PubMed2002

Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin.

Lymphomatoid papulosis (LyP) represents an intriguing cutaneous T-cell lymphoproliferative disorder with a histologic appearance resembling malignant lymphoma. This finding strongly contrasts with the benign clinical course of the disease. However, in 10% to 20% of cases, LyP can precede, coexist with, or follow malignant lymphoma. In these cases, the same T-cell population has been shown to be present in the LyP as well as in the associated lymphoma. In most LyP cases, there is-despite the sometimes extremely long course of the disease-no evolution of a secondary lymphoma. The investigation of these uncomplicated LyP cases for the presence of clonal T-cell receptor rearrangements has produced heterogeneous results. This might be explained by biologic or technical reasons arising from analyzing whole tissue DNA extracts. To definitively clarify whether the large atypical CD30(+) cells in LyP without associated lymphoma all belong to the same clone or represent individually rearranged T cells, we analyzed the T-cell receptor-gamma rearrangements of single CD30+ as well as of single CD30- cells isolated from 14 LyP lesions of 11 patients. By using this approach we could demonstrate that the CD30+ cells represent members of a single T-cell clone in all LyP cases. Moreover, in 3 patients the same CD30+ cell clone was found in anatomically and temporally separate lesions. In contrast, with only a few exceptions, the CD30- cells were polyclonal in all instances and unrelated to the CD30+ cell clone. Our results demonstrate that LyP unequivocally represents a monoclonal T-cell disorder of CD30+ cells in all instances.

Adult↗
PubMed2000

Characterization of superantigen-induced clonal deletion with a novel clan III-restricted avian monoclonal antibody: exploiting evolutionary distance to create antibodies specific for a conserved VH region surface.

Evolution of the Ab system has yielded three clans of VH region genes that are represented in almost every known higher species with an adaptive immune system. These clans are defined by sequence homologies primarily in highly conserved framework (FR) subdomains, which serve a scaffolding function maintaining the conformation of loops responsible for Ag binding. Structural analyses indicate that the VH FR1 and FR3 form a conserved composite exposed surface, which has been implicated in interactions with B cell superantigens. To directly investigate the expression of clan-defined supraclonal sets, we exploited the evolutionary distance of the chicken immune system and the selection power of phage display, to derive Abs diagnostic for clan III Ig. Using a specially tailored immunization and selection strategy, we created recombinant avian single chain Fv Abs specific for the clan III products, including those from the human VH3 family, and the analogous murine 7183, S107, J606, X24, and DNA4 families, and binding was competitive with natural B cell superantigens. The archetype, LJ-26, was demonstrated to recognize a clan-specific surface expressed in diverse mammalian, and also the Xenopus and chicken, immune systems. In flow-cytometric studies with LJ-26, we found that treatment of heterozygous T15i transgenic mice with a model B cell superantigen induced a clan III-restricted clonal deletion. These studies demonstrate the utility of a novel recombinant serologic reagent to study the composition of the B cell compartment and also the consequences of B cell superantigen exposure.

Amino Acid Sequence↗
PubMed1999

Superbugs: How They Evolve and Minimize the Cost of Resistance.

The increasing frequency with which antimicrobial-resistant microorganisms have emerged in hospitals and communities has alarmed public health officials worldwide. The emergence of resistance results from the evolution of the sometimes elegant resistance mechanisms that create so-called superbugs, which disseminate by clonal spread or exchange resistance traits with other microorganisms. One major contributor to the emergence of resistance is selection intensity, which is determined by the volume of drug consumption by humans and the agriculture industry. De novo or acquired resistance is often initially associated with a cost to fitness of the microorganism. It therefore seems reasonable to assume that reducing the volume of drug use would slow the evolution and reduce the prevalence of resistance. This assumption has led to worldwide attempts to control the inappropriate use of antimicrobials in the hope of controlling the pandemic of antibiotic resistance. However, microorganisms have learned to adapt in order to survive in ever-changing environments. Superbugs have evolved numerous mechanisms that reduce or eliminate the cost of resistance, and such adaptations may minimize the potential benefits of programs aimed at reducing the volume of drug use. It therefore behooves us to look to other disciplines--such as population genetics, ecology, and mathematical biology--to help us tackle this perplexing and important problem.

Journal Article↗
PubMed1996

CD30-positive cutaneous large cell lymphomas. A comparative study of clinicopathologic and molecular features of 16 cases.

The authors have analyzed and compared the clinicopathologic and molecular features of 16 cases of large cell cutaneous lymphomas expressing CD30 antigen. Three main clinical groups were defined: (1) a group of localized skin disease (7 cases); (2) a group of multicentric skin disease (5 cases); and (3) a group of concomitant skin and extracutaneous disease. Good prognosis was associated with localized skin disease and no history of lymphoma. Interestingly, a majority of Reed Sternberg-like cells was only observed in this group (5 of 6 cases). The two other groups did not show distinctive evolutive nor morphologic features. Southern blot and/or polymerase chain reaction (PCR) technique showed clonality and a T-cell genotype in respectively 13 of 14 and 12 of 12 analyzed cases. Viral infection of tumoral cells was investigated by PCR, in situ hybridization (ISH) or electron microscopy. Epstein-Barr virus (EBV) sequences were detected by PCR and ISH in tumoral cells of cutaneous lesions in one case of skin lymphoma with extracutaneous spreading. No EBV sequence was detected by ISH in the localized lymphomas, whereas HIV particles were visible in tumoral cells in one of these cases. No human T-cell lymphotropic virus (HTLV) tax sequence was amplified by PCR in any case of our series. Our results confirm that CD30-positive cutaneous large cell lymphomas are different clinical and molecular entities. However, a combined clinical and morphologic analysis may help to identify a subset of CD30 cutaneous lymphomas with favorable prognosis.

Adolescent↗
PubMed1992

Molecular studies on the aerolysin gene of Aeromonas species and discovery of a species-specific probe for Aeromonas trota species nova.

A large group of aeromonads and other enteric microorganisms were assayed for the presence of the aerolysin gene with use of DNA-DNA hybridization. Two DNA fragments corresponding to the regulatory region (aerC) and the structural gene (aerA) were used as probes for the detection of the aerolysin gene in these strains. Sequences corresponding to the aerolysin structural gene were widespread among Aeromonas isolates. In contrast, the aerC probe was much more selective, and sequences corresponding to the aerC region were detected in only a small subset of strains. Concurrent studies using numerical taxonomy and DNA hybridization with the aerC probe on a larger set of strains led to the identification of a distinct cluster of 14 presumed atypical Aeromonas sobria strains. These strains have recently been grouped into a new species designated Aeromonas trota. Hence, the DNA fragment aerC used in the study is a species-specific gene probe for A. trota. The ability of the aerC probe to detect strains belonging to a single species suggests that there is selection pressure to maintain the clonality of this species. These results have important implications with respect to the evolution of "pathogenic profiles" among these medically important bacteria.

Aeromonas↗
PubMed2002

[Analysis of sister chromatid differentiation in myelodysplastic syndrome and its clinical application].

OBJECTIVE: To verify the value of sister chromatid differentiation (SCD) analysis of bone marrow cells in establishing the diagnosis and predicting prognosis of myelodysplastic syndrome (MDS). METHODS: S-bromodeoxyuridine-SCD and karyotyping studies were performed in 50 cases with clinically suspected MDS. RESULTS: Prolonged cell cycle time (CT) was found in 33 of the 50 cases (66.0%). In 13 cases with acute myeloid leukemia (AML), all had prolonged CT. However, only 2 (10.5%) of the 19 cases with nonmalignant hematological disorders had prolonged CT. There were significant differences of CT between the cases with MDS and those with AML, aplastic anemia (AA) and benign hypercellular anemias as well as healthy individuals. However, there were no significant differences between healthy individuals and cases with AA and, with benign hepercellular anemia. CT gradually prolonged during the evolution of MDS. 24 of the 50 patients (48.0%) were found to have clonal chromosomal abnormalities. In seven cases not compatible with MDS according to FAB criteria, six were found to have clonal chromosomal abnormalities. The mortality rates were 11.8 and 50.0% in the groups of normal SCD and of prolonged SCD, respectively (P < 0.05). The rates of leukemia transformation in both the groups were 5.9% and 16.7% (P > 0.05). The median survival of both the groups was 12 months and 8 months (P = 0.051). CONCLUSION: SCD analysis is valuable for establishing the diagnosis and predicting the prognosis of MDS.

Adolescent↗
PubMedDate not supplied

The point on myelodysplastic syndromes.

The Myelodysplastic Syndromes (MDS) are heterogeneous borderline diseases, with propensity to transform into acute leukemia. Some paradoxes need more attention either in experimental and clinical approach: the clonal proliferation, involving all the hematopoietic lines, but associated with a relatively long evolution which ends not always into acute leukemia; involvement of cytokines, but a poor therapeutical response to anti-cytokine therapy; the surprisingly good effect of the "differentiating "drugs in vitro and the poor response in vivo. The prognostic scores according to cytological, histological and genetic criteria, and the therapeutical approach are discussed.

Humans↗
PubMed2004

Self-representation in the thymus: an extended view.

The thymus has been viewed as the main site of tolerance induction to self-antigens that are specifically expressed by thymic cells and abundant blood-borne self-antigens, whereas tolerance to tissue-restricted self-antigens has been ascribed to extrathymic (peripheral) tolerance mechanisms. However, the phenomenon of promiscuous expression of tissue-restricted self-antigens by medullary thymic epithelial cells has led to a reassessment of the role of central T-cell tolerance in preventing organ-specific autoimmunity. Recent evidence indicates that both genetic and epigenetic mechanisms account for this unorthodox mode of gene expression. As we discuss here, these new insights have implications for our understanding of self-tolerance in humans, its breakdown in autoimmune diseases and the significance of this tolerance mode in vertebrate evolution.

Animals↗
PubMed2025

Climate-driven co-evolution of antimicrobial resistance and virulence in Escherichia coli on dairy farms: unraveling adaptive genetic signatures with novel SSCP-PCR.

This study addresses a critical One Health challenge by investigating the epidemiological and genetic drivers of antimicrobial resistance (AMR) in E. coli from 290 clinical bovine samples. On Egyptian dairy farms, our findings revealed that while calf diarrhea peaked during the winter, a higher rate of multidrug resistance was consistently observed in isolates from the summer, directly linking seasonal pressures to AMR dissemination. Strikingly, a mastitis isolate was confirmed as the highly virulent E. coli O157:H7 serotype, harboring the Shiga toxin genes stx1 and stx2, underscoring a direct and significant public health risk. To dissect the molecular basis of these trends, we pioneered the use of a novel Single-Strand Conformation Polymorphism Polymerase Chain Reaction (SSCP-PCR) assay on 33 selected isolates. This high-throughput approach revealed prevalent mutations in resistance genes (blaTEM and gyrB) and the virulence gene (fimH). Crucially, sequencing confirmed that mutations in the highly conserved 16S rRNA gene significantly co-occurred with mutations in blaTEM, fimH, and lacI, providing compelling evidence for co-selected adaptive pathways and clonal expansion. Our research demonstrates that climate-driven environmental pressures fuel the co-evolution of AMR and virulence on farms, championing SSCP-PCR as a robust tool for tracking microbial evolution and advocating for integrated, molecularly-informed One Health strategies.

Escherichia coli↗
PubMed1993

Genome macrorestriction analysis of diversity and variability of Pseudomonas aeruginosa strains infecting cystic fibrosis patients.

Genome macrorestriction fingerprinting with XbaI and DraI was used to analyze the relatedness of 166 Pseudomonas aeruginosa isolates collected from 31 cystic fibrosis patients over a 1- to 20-month period and to correlate their genotype with patterns of resistance to 14 antimicrobial agents. Quantitative comparison of intra- and interpatient similarities of P. aeruginosa macrorestriction patterns disclosed two discrete ranges that clearly discriminated subclonal variation (> 80% relatedness) and clonal diversity (10 to 70% relatedness). Cloning-derived mutants exhibited up to 20% divergence of genomic macrorestriction patterns during the course of chronic colonization of individual patients. Change of susceptibility to multiple antimicrobial agents developed in 50% of sequential pairs of isolates from individual patients. Only 19% of these susceptibility changes were attributable to strain substitution, while the majority (56%) of resistance changes were associated with minor genomic variations of a persistent strain. Sixty-six percent of patients harbored one strain, and 33% carried two strains. Three common strains colonized 5 (28%) of 18 patients attending a cystic fibrosis clinic, and another two strains colonized two patient pairs (31%) of 13 patients staying at a rehabilitation center, suggesting potential cross-infection in these settings. By indexing regional polymorphisms throughout the chromosome structure, macrorestriction analysis can monitor subclonal evolution of P. aeruginosa and identify isogenic resistance mutants. Quantitative macrorestriction fingerprinting enables discrimination between clonal variants and clones of distinct origins and should therefore provide a reliable tool for investigating the mode of acquisition of P. aeruginosa in cystic fibrosis patients.

Cross Infection↗