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At least 1,225 records · Page 68Linked to original sources
PubMed2004

Continuing diversification of Neisseria meningitidis W135 as a primary cause of meningococcal disease after emergence of the serogroup in 2000.

The occurrence of a clonal outbreak of serogroup W135 (of the electrophoretic type 37 [ET-37] clonal complex) meningococcal disease among Hajj pilgrims in 2000 has led to enhanced surveillance of the evolution of this particular serogroup, formerly considered rare, in invasive infections. Since the first case of meningococcal disease due to a serogroup W135 strain was detected in France in 1994, all isolates were characterized phenotypically. We further used phenotypic and genotypic approaches to type the 101 serogroup W135 strains isolated from patients with invasive meningococcal diseases in France in 2001 and 2002. Overall, 55% of these isolates had Hajj strain-related phenotypes (60 and 52% in 2001 and 2002, respectively), although only 45% belonged to the ET-37 clonal complex. Moreover, pulsed-field gel electrophoresis of the ET-37 clonal complex isolates showed that only 32% of the serogroup W135 isolates were indistinguishable from the 2000 Hajj-related strain. Our results suggest the continuous emergence of new genetic lineages of serogroup W135 independently of the 2000 global outbreak.

Bacterial Typing Techniques↗
PubMed1991

Karyotype evolution of Ph positive chronic myelogenous leukemia patients relapsed in advanced phases of the disease after allogeneic bone marrow transplantation.

Sixty-eight patients affected by Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) and were successfully studied from a cytogenetic point of view, before and after the BMT. Nineteen had evidence of cytogenetic and clinical relapse. Cytogenetic analyses of 14 patients who, after the relapse, showed progression to the accelerated or blastic phase of the disease, are presented. Five of these cases had only the Ph chromosome without karyotype evolution; in one case Ph duplication without other anomalies was detected, while in the remaining eight cases cytogenetic analysis showed apparently random clonal structural abnormalities (translocations, inversions, deletions, and marker formations). Therefore, the classical "non-random" abnormalities (+8, i(17q), +Ph, +19, +21) were not as common as in conventionally treated Ph+ CML. From our data, karyotype evolution during advanced phases in Ph+ CML patients after BMT differs from the evolution seen in conventionally treated patients, by the presence of numerous structural unusual abnormalities, possibly related to radiochemotherapy conditioning to BMT. Therefore, BMT treatment is not always able to eradicate the Ph+ clone but can reduce the incidence of the formation and/or expansion of Ph+ clones with additional non-random abnormalities.

Bone Marrow Transplantation↗
PubMed2000

Dominant role of host selective pressure in driving hepatitis C virus evolution in perinatal infection.

The dynamics of the genetic diversification of hepatitis C virus (HCV) populations was addressed in perinatal infection. Clonal sequences of hypervariable region 1 of the putative E2 envelope protein of HCV were obtained from four HCV-infected newborns (sequential samples spanning a period of 6 to 13 months after birth) and from their mothers (all samples collected at delivery). The data show that the variants detected between birth and the third month of life in samples from the four newborns were present in the HCV populations of their mothers at delivery. In the newborns, a unique viral variant (or a small group of closely related variants) remained stable for weeks despite active viral replication. Diversification of the intrahost HCV population was observed 6 to 13 months after birth and was substantially higher in two of the four subjects, as documented by the intersample genetic distance (GD) (P = 0.007). Importantly, a significant correlation between increasing GD and high values for the intersample K(a)/K(s) ratio (the ratio between anoffymous and synonymous substitutions; an index of the action of selective forces) was observed, as documented by the increase of both parameters over time (P = 0.01). These data argue for a dominant role of positive selection for amino acid changes in driving the pattern of genetic diversification of HCV populations, indicate that the intrahost evolution of HCV populations is compatible with a Darwinian model system, and may have implications in the designing of future antiviral strategies.

Amino Acid Sequence↗
PubMed2001

Molecular, cytogenetic and genetic abnormalities in MDS and secondary AML.

Myelodysplasia (MDS) is a clonal disease, which increases with age, suggesting that multiple steps are required for the evolution of the condition. Approximately 30% of MDS evolve into acute myelogenous leukemia (AML). In this review, we intend to delineate the genetic events, which may drive this sequence and therefore we will focus primarily on cytogenetic abnormalities where the genes have been identified and oncogenes and suppressor genes that have been implicated. In terms of the biological mechanisms, which characterise this process, it is generally thought that the MDS cell has impaired differentiation, and has increased apoptosis. As the disease progresses in addition, the cells have increased proliferation. As the disease evolves, the population of cells, which predominate remain immature, have decreased apoptosis and in many cases, upregulate anti-apoptotic genes and have deregulated proliferation as the number of blast cells increase. Etiological factors, which contribute to the development of leukemia, include therapeutic agents administered for a primary malignancy. The cytogenetic abnormalities, predisposition factors and genes involved in secondary leukemia will also be reviewed.

Acute Disease↗
PubMed2006

Toward a Wolbachia multilocus sequence typing system: discrimination of Wolbachia strains present in Drosophila species.

Among the diverse maternally inherited symbionts in arthropods, Wolbachia are the most common and infect over 20% of all species. In a departure from traditional genotyping or phylogenetic methods relying on single Wolbachia genes, the present study represents an initial Multilocus Sequence Typing (MLST) analysis to discriminate closely related Wolbachia pipientis strains, and additional data on sequence diversity in Wolbachia. We report a new phylogenetic characterization of four genes (aspC, atpD, sucB, and pdhB), and provide an expanded analysis of markers described in previous studies (16S rDNA, ftsZ, groEL, dnaA, and gltA). MLST analysis of the bacterial strains present in 16 different Drosophila-Wolbachia associations detected four distinct clonal complexes that also corresponded to maximum-likelihood identified phylogenetic clades. Among the 16 associations analyzed, six could not be assigned to MLST clonal complexes and were also shown to be in conflict with relationships predicted by maximum-likelihood phylogenetic inferences. The results demonstrate the discriminatory power of MLST for identifying strains and clonal lineages of Wolbachia and provide a robust foundation for studying the ecology and evolution of this widespread endosymbiont.

Animals↗
PubMed1996

Predominance of defective proviral sequences in an HIV + long-term non-progressor.

We examined the accessory genes and envelope V3 region of provirus obtained over a 5 year period from an HIV+ long-term non-progressor with very low viral load and no in vitro recoverable virus during that same time span. LTR sequences supported normal Tat-mediated promoter activity. Multiple clones of nef sequences were highly conserved with < 10% containing frame shift or stop codon mutations. Functional analysis of the predominant nef sequence indicated wild type downregulation of surface CD4 and good function in a complementation infectivity assay. By contrast, inactivating mutations were found in 64% of amplicons containing vif, vpr, vpu, tat1, and rev1, and in 41% of amplicons containing env V3. Identical inactive sequences were obtained at an interval of 2 years, suggesting persistence of quiescent defective provirus in a long-lived clonal cell population. Furthermore, genetic distance versus time analysis revealed an absence of progressive evolution or arborization of quasispecies over time. This contrasts with data generated from other asymptomatic HIV+ individuals. The non-progressive pattern of env sequence diversity and low R2 for genetic divergence over time suggests that the defective provirus circulating in the periphery of this patient represents a randomly sampled 'fossil record' of earlier replication competent HIV-1 genomes.

Defective Viruses↗
PubMed2001

MHC-restricted and -unrestricted CD8 T cells: an evolutionary perspective.

BACKGROUND: In mammals, cytotoxic CD8 T cells are crucial effectors of a typical adaptive cellular immune response. They recognize and kill cells that express at their surface antigenic peptides complexed to major histocompatibility complex (MHC) class I molecules. Although T cells (undefined as to CD determinants) and associated in vitro cytotoxic activity have been described in a few amphibian and teleost species, their in vivo functions have yet to be characterized. METHODS AND RESULTS: CD8 function has been investigated in the frog Xenopus by antibody depletion, skin allografting, and tumor transplantation. Injection of adult frogs with anti-Xenopus CD8 monoclonal antibody effects transient CD8 T-cell depletion in vivo that correlates with delayed rejection of MHC-disparate skin allografts and an impaired immune response against transplanted syngeneic MHC class I-negative tumors. CONCLUSIONS: For the first time, CD8 T cells have been shown to be involved in acute skin allograft rejection in an ectothermic vertebrate. Our data also suggest that, at least in Xenopus, T cells that express a CD8 epitope may be effectors in MHC-unrestricted anti-tumor responses.

Animals↗
PubMed2026

Comparative genomics reveals lineage-associated structural variation and diversification in a barley fungal pathogen.

Leaf rust, caused by Puccinia hordei, is a major barley disease worldwide. Despite repeated shifts in virulence, contrasting reproductive histories, and emerging fungicide insensitivity, the genomic basis of its diversification and adaptation remains poorly understood. In this study, we generated haplotype-resolved, chromosome-level genome assemblies for two isolates with contrasting virulence and analyzed 41 Australian isolates collected over 54&#x2009;yr (1966-2020), integrating comparative and population genomics, mating-type gene phylogenies, chromosome-specific k-mer profiling, genome-wide copy-number variation (CNV) analysis, and gene-expression analysis. We identified a structurally dynamic chromosome characterized by repeat-associated rearrangements, structural variation, and lineage-associated CNV, representing the first evidence in a rust fungus of chromosome-scale structural diversification of this extent. Population analyses distinguished clonally expanded lineages from recombination-associated lineages, with mating-type gene phylogenies providing further support for lineage differentiation. More recently collected isolates showed increased duplication-associated variation, and CNV boundaries were associated with structural-variant breakpoints. We also identified lineage-associated amplification of Cyp51, with increased copy number associated with higher transcript abundance, supporting a potential role in fungicide adaptation. Overall, our findings highlight structural variation, contrasting reproductive histories, and lineage-associated CNV as important contributors to diversification in P. hordei, providing insights for future rust pathogen surveillance and management strategies.

Cyp51 gene↗
PubMed1982

Biological diversity in metastatic neoplasms: origins and implications.

Whether neoplasms are unicellular or multicellular in their origin, the process of tumor evolution and progression can rapidly generate biological diversity. Metastases result from the survival and proliferation of specialized subpopulations of cells within the parent tumor. Metastases may have a clonal origin and different metastases may develop from different progenitor cells. However, as with the primary tumor, the origin of metastases is unimportant since the process of tumor evolution and progression can generate biological diversity within and among different metastatic foci.

Animals↗
PubMed2005

["Chain" karyotypic evolution of embryonic stem cell line R1 in vitro].

Cytogenetic anomaly frequencies were analysed in three sublines of ES R1 line in its five clonal sublines, obtained from two cell colonies after transformation of ES R1 cells by plasmid with gene lif. Cell transformation did not increase cytogenic anomalies, however, the initial sublines of ES R1 line, as well as its transformed clonal descendants bore a redundant quantity of the chromosome 8 material within the structure of various Robertsonian translocations even in cells with diploid chromosome quantity (2n = 40). In the initial sublines ES R1 and its clonal descendants a common Rb (8; 15) was revealed. It was supposed that selection for the increase in ES cell sensitivity to cytokines (in particular, LIF) under cultural conditions was accompanied by an increase in chromosomal copies, carrying genes of mapk andjak/stat, through which downstream effectors of cytokine signals for preservation of cell pluripotention and propagation are realized. Genes of chromatid separation and chromosome segregation control (for example, separase gene Esp1 in chromosome 15) may be passively involved in this process, thus promoting acceleration of karyotype evolution in ES cells.

Animals↗
PubMed2006

Deterministic and stochastic regimes of asexual evolution on rugged fitness landscapes.

We study the adaptation dynamics of an initially maladapted asexual population with genotypes represented by binary sequences of length L. The population evolves in a maximally rugged fitness landscape with a large number of local optima. We find that whether the evolutionary trajectory is deterministic or stochastic depends on the effective mutational distance d(eff) up to which the population can spread in genotype space. For d(eff) = L, the deterministic quasi-species theory operates while for d(eff) < 1, the evolution is completely stochastic. Between these two limiting cases, the dynamics are described by a local quasi-species theory below a crossover time T(x) while above T(x) the population gets trapped at a local fitness peak and manages to find a better peak via either stochastic tunneling or double mutations. In the stochastic regime d(eff) < 1, we identify two subregimes associated with clonal interference and uphill adaptive walks, respectively. We argue that our findings are relevant to the interpretation of evolution experiments with microbial populations.

Adaptation, Biological↗
PubMed2006

Mutations, mutation rates, and evolution at the hypervariable VNTR loci of Yersinia pestis.

VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing approximately 96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database.

Animals↗
PubMed2002

Microevolution of the direct repeat region of Mycobacterium tuberculosis: implications for interpretation of spoligotyping data.

The direct repeat (DR) region has been determined to be an important chromosomal domain for studying the evolution of Mycobacterium tuberculosis. Despite this, very little is known about microevolutionary events associated with clonal expansion and how such events influence the interpretation of both restriction fragment length polymorphism (RFLP) and spoligotype data. This study examined the structure of the DR region in three independently evolving lineages of M. tuberculosis with a combination of DR-RFLP, spoligotyping, and partial DNA sequencing. The results show that the duplication of direct variable repeat (DVR) sequences and single-nucleotide polymorphisms is rare; conversely, the deletion of DVR sequences and IS6110-mediated mutation is observed frequently. Deletion of either single or contiguous DVR sequences was observed. The deletion of adjacent DVR sequences occurred in a dependent manner rather than as an accumulation of independent events. Insertion of IS6110 into either the direct repeat or spacer sequences influenced the spoligotype pattern, resulting in apparent deletion of DVR sequences. Homologous recombination between adjacent IS6110 elements led to extensive deletion in the DR region, again demonstrating a dependent evolutionary mechanism. Different isolates from the same strain family and isolates from different strain families were observed to converge to the same spoligotype pattern. In conclusion, the binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of M. tuberculosis. This has important implications for molecular epidemiologic strain tracking and for the application of spoligotype data to phylogenetic analysis of M. tuberculosis isolates.

Bacterial Typing Techniques↗
PubMed2004

Keeping sensory cells and evolving neurons to connect them to the brain: molecular conservation and novelties in vertebrate ear development.

The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an 'organ' system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.

Animals↗
PubMed2006

Genetic variability and adaptive evolution in parthenogenetic root-knot nematodes.

Root-knot nematodes (RKN) of the genus Meloidogyne are biotrophic plant parasites of major agricultural importance, which exhibit very variable modes of reproduction, from classical amphimixis to mitotic parthenogenesis. This review focuses on those RKN species that reproduce exclusively by mitotic parthenogenesis (apomixis), in contrast to those that have meiotic/amphimitic events in their life cycle. Although populations of clonal organisms are often represented as being ecologically isolated and evolutionary inert, a considerable volume of literature provides evidence that asexual RKN are neither: they are widely distributed, extremely polyphagous, and amenable to selection and adaptive variation. The ancestors of the genus are unknown, but it is assumed that the parthenogenetic RKN have evolved from amphimictic species through hybridization and subsequent aneuploidization and polyploidization events. Molecular studies have indeed confirmed that the phylogenetic divergence between meiotic and mitotic RKN lineages occurred early, and have revealed an unexpected level of clonal diversity among populations within apomictic species. Laboratory experiments have shown that asexual RKN can rapidly adapt to new environmental constraints (eg host resistance), although with some fitness costs. Lastly, the molecular and chromosomal mechanisms that could contribute to genome plasticity leading to persistent genetic variation and adaptive evolution in apomictic RKN are discussed. It is concluded that RKN provide an excellent model system in which to study the dynamic nature and adaptive potential of clonal genomes.

Adaptation, Physiological↗
PubMed1994

Karyotype evolution in a patient with Down syndrome and acute leukemia following a congenital leukemoid reaction.

We report the serial cytogenetic study of a patient with Down syndrome who experienced a congenital leukemoid reaction, underwent a spontaneous remission within four months, and subsequently developed acute myeloid leukemia at 16 months. A blood chromosome study to rule out Down syndrome performed at age 24 days, during the leukemoid reaction, revealed a 47,XX,+21 karyotype. The diagnosis of acute leukemia was made at 16 months, at which time a chromosome study, on bone marrow, was performed. This analysis revealed a clonal karyotype of 47,XX,+21,-22,+der(22)t(1;22)(q21;q13) in all but one cell studied. The single apparently nonclonal cell showed a karyotype of 49,XX,+12,-13,-19,+der(19)t(19;?)(q11;?)x2,+21,+22. A third chromosome study at 19 months indicated the original leukemic clone with t(1;22) (q21;q13) had been replaced by the clone represented by the single cell with 49 chromosomes seen in the previous chromosome study. This case of an infant with Down syndrome and acute leukemia illustrated rapid evolution and a transitory nature to clonal chromosome aberrations while retaining AML morphology and course.

Acute Disease↗
PubMed1998

Clonality Studies in the Analysis of Adrenal Medullary Proliferations: Application Principles and Limitations.

Clonality remains as the hallmark of neoplasms. A dual genetic approach using markers nonrelated (e.g., X-chromosome inactivation assays) and related to the malignant transformation (such as loss of heterozygosity analyses of tumor-suppressor genes) would provide useful clonality information from early and advanced tumor stages, respectively. Tumor progression and clonal selection would result in genetic instability and heterogeneous expression of those molecular markers related to the malignant pathway. Therefore, only the coexistence of multiple genetic abnormalities would support the clonal nature as an expression of convergent cell selection. Considering those facts, the currently available evidence on tumorigenesis and clonality in the adrenal medulla can be summarized as follows: 1. Multistep tumorigenesis defines the evolution of pheochromocytomas, as evidenced by the presence of several genetic alterations. 2. Both the significant association of nonrandom genetic alterations (specially 1p and 22q interstitial deletions) and the topographic accumulation of genetic deletions at the peripheral tumor compartment support a convergent clone selection for these neoplasms. 3. Although many genetic loci show nonrandom abnormalities, the most frequently involved locates on chromosome 1p regardless of genetic tumor background (sporadic or inherited predisposition). 4. Most pheochromocytomas should begin as monoclonal proliferations that do not always correlate with histopathologic features, particularly in inherited tumor syndromes. 5. Early histopathologic stages, described as adrenal medullary hyperplasias, are defined by hyperproliferative features in animal models and monoclonal patterns in the adrenal nodules from patients with MEN-2a.

Journal Article↗
PubMed2005

Evidence for recombination in Candida glabrata.

Despite its clinical importance, little is known of the epidemiology and population structure of Candida glabrata. C. glabrata possesses a mating type system similar to that in Saccharomyces cerevisiae, however mating, meiosis and recombination have not been demonstrated. We performed multilocus sequence typing on a collection of 165 isolates to test for evidence of genetic recombination. A total of 3345 bp from six loci (FKS, LEU2, NMT1, TRP1, UGP1, and URA3) were sequenced for each isolate. The polymorphisms at these loci defined 34 sequence types. Significant evidence for a clonal population was revealed by the index of association and the number of phylogenetically compatible pairs of loci. However, 14 examples of phylogenetic incompatibility were also found. Thus we conclude that although C. glabrata has a predominantly clonal population structure, the multiple phylogenetic incompatibilities found strongly suggest that recombination occurred during the evolution of C. glabrata, and may infrequently still occur.

Candida glabrata↗