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PubMed2001

Evolution in action through hybridisation and polyploidy in an Iberian freshwater fish: a genetic review.

The Iberian minnow Leuciscus alburnoides represents a complex of diploid and polyploid forms with altered modes of reproduction. In the present paper, we review the recent data on the origin, reproductive modes, and inter-relationships of the various forms of the complex, in order to predict its evolutionary potential. The complex follows the hybrid-origin model suggested for most other asexual vertebrates. Diploid and triploid females from the southern river basins exhibit reproductive modes that cannot be conveniently placed into the categories generally recognised for these vertebrate complexes, which imply continuous shifting between forms, where genomes derived from both parental ancestors are cyclically lost, gained or replaced. Replacement of nuclear genomes allow the introduction of novel genetic material, that may compensate for the disadvantages of asexual reproduction. Contrasting with most other vertebrate complexes, L. alburnoides males are fertile and play an important role in the dynamics of the complex. Moreover, diploid hybrid males may have initiated a tetraploidization process, when a diploid clonal sperm fertilised a diploid egg. This direct route to tetraploidy by originating fish with the right constitution for normal meiosis (symmetric), may eventually lead to a new sexually reproducing polyploid species. This case-study reinforces the significance of hybridisation and polyploidy in evolution and diversification of vertebrates.

Animals↗
PubMedDate not supplied

[Alkylating damage by dipin of hematopoietic and stromal cells of the bone marrow].

Effect of alkylating agent dipin was studied on hematopoietic (CFU-S) and stromal (CFU-F) progenitor cells. Single administration of dipin (0.06 mg/g) to adult (CBAxC57Bl/6) F1 hybrid mice induced a long-term (2 years) oscillations in the numbers of day 7 CFU-S and day 11 CFU-S in the bone marrow and spleen. Dipin also damaged the hematopoietic stroma as indicated by decreased numbers of CFU-F which remained low for at least a year. The capacity of stromal cells to form ectopic hematopoietic foci was considerably inhibited and also remained low for 10 months. The obtained data suggest high dipin sensitivity of the earliest hematopoietic and stromal cells. The dynamics of CFU-S numbers in the hematopoietic organs supports their functioning on the basis of clonal succession (Kay, 1965).

Animals↗
PubMed2006

High-content kinetic calcium imaging in drug-sensitive and drug-resistant human breast cancer cells.

Intracellular calcium (Ca2+) is involved in the regulation of a variety of biological functions in cancer cells, including growth inhibition, tumor invasiveness, and drug resistance. To gain insight into the possible role played by Ca2+ in the development of drug resistance in breast cancer, we performed a comparative high-content analysis of the intracellular Ca2+ dynamics in drug-sensitive human breast cancer MCF-7 cells and five drug-resistant, MCF-7-derived clonal cell lines. Fura-2 single cell ratiometric fluorescence microscopy was used to monitor real-time quantitative changes in cytosolic-free Ca2+ concentration ( [Ca2+]i ) upon addition of phosphoinositol-coupled receptor agonists. While the magnitude and the onset kinetics of the [Ca2+]i rise were similar in drug-sensitive and drug-resistant cell lines, the decay kinetics of the [Ca2+]i increase was found to be consistently slower in drug-resistant than drug-sensitive cells. Such a delay in reestablishing homeostatic [Ca2+]i persisted in the absence of extracellular Ca2+ and was independent of the expression or function of specific drug efflux pumps associated with drug resistance. Moreover, intracellular Ca2+ pools releasable by phosphoinositol-coupled receptor agonists or thapsigargin appeared to be differentially shared in drug-sensitive and drug-resistant cells. In light of the clinical relevance that drug resistance has in the treatment of cancer, the molecular and biochemical relationship between alterations in Ca2+ dynamics and drug resistance demands to be further investigated and tested in a wider array of cell types. Automated microscopy will help greatly in this pursuit by facilitating both sample imaging and data analysis, thus allowing high-content as well as high-throughput screening of large sample sets. A protocol for studying [Ca2+]i kinetics with a commercially available automated imaging platform is described.

Automation↗
PubMed2003

Rapid evolution drives ecological dynamics in a predator-prey system.

Ecological and evolutionary dynamics can occur on similar timescales. However, theoretical predictions of how rapid evolution can affect ecological dynamics are inconclusive and often depend on untested model assumptions. Here we report that rapid prey evolution in response to oscillating predator density affects predator-prey (rotifer-algal) cycles in laboratory microcosms. Our experiments tested explicit predictions from a model for our system that allows prey evolution. We verified the predicted existence of an evolutionary tradeoff between algal competitive ability and defence against consumption, and examined its effects on cycle dynamics by manipulating the evolutionary potential of the prey population. Single-clone algal cultures (lacking genetic variability) produced short cycle periods and typical quarter-period phase lags between prey and predator densities, whereas multi-clonal (genetically variable) algal cultures produced long cycles with prey and predator densities nearly out of phase, exactly as predicted. These results confirm that prey evolution can substantially alter predator-prey dynamics, and therefore that attempts to understand population oscillations in nature cannot neglect potential effects from ongoing rapid evolution.

Animals↗
PubMed2000

Adaptive dynamics in diploid, sexual populations and the evolution of reproductive isolation.

Evolutionary branching is the process whereby an initially monomorphic population evolves to a point where it undergoes disruptive selection and splits up into two phenotypically diverging lineages. We studied evolutionary branching in three models that are ecologically identical but that have different genetic systems. The first model is clonal, the second is sexual diploid with additive genetics on a single locus and the third is like the second but with an additional locus for mate choice. Evolutionary branching occurred under exactly the same ecological circumstances in all three models. After branching the evolutionary dynamics may be qualitatively different. In particular, in the diploid, sexual models there can be multiple evolutionary outcomes whereas in the corresponding clonal model there is only one. We showed that evolutionary branching favours the evolution of (partial) assortative mating and that this in turn effectively restores the results from the clonal model by rendering the alternative outcomes unreachable except for the one that also occurs in the clonal model. The evolution of assortative mating during evolutionary branching can be interpreted as the initial phase of sympatric speciation with phenotypic divergence and partial reproductive isolation.

Adaptation, Physiological↗
PubMed1994

Might stochasticity and sampling variation be a possible explanation for variation in clonal population survival curves.

Biogerontological survival analysis attempts to understand, through the use of mathematical and computer models, how biological and environmental processes affect the dynamics of survival. The survival model parameters are assumed to reflect an average or mean response to some intervention. Further, these parameters are usually assumed to be constant over the time course of the experiment and across the elements of the experimental cohort. In this paper, we introduce stochastic (random) features to the survival curve parameters and we observe how this might affect our interpretation of the biology; as reflected in the estimates of the model parameters. In particular, we provide a possible explanation for variation in parameter estimates within sample populations drawn from a population of genetic clones.

Computer Simulation↗
PubMed1999

Loss of pathogenic potential after cloning of the low-passage Borrelia burgdorferi ZS7 tick isolate: a cautionary note.

To study clonal polymorphism of Borrelia hurgdorferi antigens in the course of an experimental infection sequence, the low-passage tick isolate ZS7 was cloned by two rounds of agar subsurface plating. The resulting clones showed a variable pathogenic potential after experimental infection of C.B-17. scid mice. The test clone 4.2.II, selected for virulence by two passages in immunodeficient scid mice, failed to establish a successful infection in immunocompetent AKR/N mice, indicating the loss of pathogenicity traits required for evasion of the specific immune response. Cloning of natural or clinical B. burgdorferi isolates is a prerequisite for analyzing genetic and antigenic variation of the pathogen. However, the inevitable propagation in artificial media during cloning may lead to a loss of pathogenic features rendering the subsequent experimental infection of animals impossible. A combined procedure of in vitro cloning and in vivo selection also does not solve the dilemma because B. burgdorferi variants arise by recombinatorial processes in the pathogen's dynamic genome during the course of infection. Consequently, the resulting bacterial isolates from infected animal tissues represent again non-clonal, heterogeneous B. burgdorferi populations. In principle, cloning of a B. burgdorferi population is the appropriate method to analyze the polymorphism of individual molecules during infection. As a caveat, however, one has to envisage that during propagation of individual clones in vitro and in vivo independent genetic variations

Animals↗
PubMed2006

Telomeres, immune aging and autoimmunity.

Telomere length is important in constraining the replicative potential of cells; cellular systems that are dependent on cell replenishment for renewal or on cell proliferation for functionality are highly sensitive to telomeric erosion. Cell replication invariably leads to telomere loss, which, in some cellular systems, is partially compensated for by telomerase activity. In addition to this typical telomere loss, several mechanisms of sporadic telomere loss exist. Heterogeneity in age-dependent telomere loss can be a consequence of increased cellular turnover during a lifetime, accelerated telomeric DNA damage, or defects in telomere repair. The immune system is a prime example of a highly dynamic cellular system, for which telomere maintenance is pivotal. Immune competence is strictly dependent on rapid expansions of clonal T- and B-cell populations, and telomere loss may contribute to defective immune responses in the elderly. Equally interestingly, accelerated T-cell aging combined with telomeric shortening may predispose for autoimmune responses and thereby explain the increased susceptibility for chronic inflammatory diseases in the elderly.

Aging↗
PubMed1987

Tumor micro-ecology and competitive interactions.

Three nested models describing the growth of individual subpopulations in a heterogeneous environment are described. The models represent the dynamics of two populations which compete, to varying degrees, for common resources. The first model describes growth in a totally non-competitive micro-environment, the second model describes an ecology in which competition is proportional to competitor population size, and the third model ecology extends the model described by Jansson & Revesz (1974), which allows one population to emerge from the other. The critical points for each model are defined using the isoclines derived from the Ordinary Differential Equations (ODE's) describing competitive growth. The critical points for each model are characterized by the signs of the eigenvalues of the variational matrix at each point. The theoretical results of the analysis show that a competitive model ecology with Verhulstian logistics allows four critical points: the origin which is a repeller, two competitive exclusion points, and an equilibrium state (Waltman, 1983). The extended model ecology of Jansson & Revesz (1974), allows three critical points: the origin which is a repeller, competitive exclusion of the first population, and an equilibrium point. Data from a human adenocarcinoma of the colon and murine mammary tumors are used as qualitative measures of the dynamics of the three micro-ecologies. Issues such as stochastic extension to model small populations either for clonal extinction or heterogeneous emergence are discussed.

Adenocarcinoma↗
PubMed1999

Population dynamics of chesapeake bay virioplankton: total-community analysis by pulsed-field gel electrophoresis

Recognition of viruses as the most abundant component of aquatic microbial communities has stimulated investigations of the impact of viruses on bacterio- and phytoplankton host communities. From results of field studies to date, it is concluded that in most aquatic environments, a reduction in the number of bacteria on a daily basis is caused by viral infection. However, the modest amount of in situ virus-mediated mortality may be less significant than viral infection serving to maintain clonal diversity in the host communities directly, through gene transmission (i.e., transduction), and indirectly, by elimination of numerically dominant host species. If the latter mechanism for controlling community diversity prevails, then the overall structure of aquatic viral communities would be expected to change as well over short seasonal and spatial scales. To determine whether this occurs, pulsed-field gel electrophoresis (PFGE) was used to monitor the population dynamics of Chesapeake Bay virioplankton for an annual cycle (1 year). Virioplankton in water samples collected at six stations along a transect running the length of the bay were concentrated 100-fold by ultrafiltration. Viruses were further concentrated by ultracentrifugation, and the concentrated samples were embedded in agarose. PFGE analysis of virus DNA in the agarose plugs yielded several distinct bands, ranging from 50 to 300 kb. Principal-component and cluster analyses of the virus PFGE fingerprints indicated that changes in virioplankton community structure were correlated with time, geographical location, and extent of water column stratification. From the results of this study, it is concluded that, based on the dynamic nature of the Chesapeake Bay virioplankton community structure, the clonal diversity of bacterio- and phytoplankton host communities is an important component of the virus community.

Journal Article↗
PubMed1993

Molecular variation in Giardia.

Molecular characterisation of species within the genus Giardia has revealed that much of the phenotypic heterogeneity, particularly within the species G. duodenalis, has a genetic basis. The source of this genetic variation appears to arise from predominantly asexual, clonal reproduction, although occasional bouts of sexual reproduction cannot be ruled out. Genetic variation is extensive with some clones widely distributed and others seemingly unique and localised to a particular endemic focus. Little attention has been given to the molecular epidemiology of Giardia infections. Future studies should be directed at studying the ecology and dynamics of transmission of Giardia clones, particularly in localised areas, and to evaluating the factors that serve to maintain genetic diversity between clones, especially the role of inter-clonal competition. Future research using molecular techniques should aim to identify and follow Giardia clones in nature and correlate genetic typing with important clinical and epidemiological characteristics such as virulence, drug sensitivity and zoonotic potential.

Animals↗
PubMed2002

Modulation of Fas-dependent apoptosis: a dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cells.

We have previously shown that regulatory CD25(+)CD4(+) T cells are resistant to clonal deletion induced by viral superantigen in vivo. In this work we report that isolated CD25(+)CD4(+) T cells activated in vitro by anti-CD3 Ab are resistant to Fas-induced apoptosis, in contrast to their CD25(-)CD4(+) counterparts. Resistance of CD25(+)CD4(+) T cells to Fas-dependent activation-induced cell death is not linked to their inability to produce IL-2 or to their ability to produce IL-10. The sensitivity of both populations to Fas-induced apoptosis can be modulated in vitro by changing the CD25(+)CD4(+):CD25(-)CD4(+) T cell ratio. The sensitivity of CD25(-)CD4(+) T cells to apoptosis can be reduced, while the sensitivity of CD25(+)CD4(+) T cells can be enhanced. Modulation of Fas-dependent apoptosis is associated with changes in cytokine production. However, while CD25(-)CD4(+) T cell apoptosis is highly dependent on IL-2 (production of which is inhibited by CD25(+)CD4(+) T cells in coculture), modulation of CD25(+)CD4(+) T cell apoptosis is IL-2 independent. Taken together, these results suggest that CD25(+)CD4(+) and CD25(-)CD4(+) T cell sensitivity to Fas-dependent apoptosis is dynamically modulated during immune responses; this modulation appears to help maintain a permanent population of regulatory T cells required to control effector T cells.

Animals↗
PubMed1990

Organization of the bacterial chromosome.

Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction between a large plasmid and a second chromosome is discussed. Recent information on repeated sequences and chromosomal rearrangements is presented. The growing understanding of limitations on the rearrangements that can be tolerated by bacteria and those that cannot is summarized, and the sensitive region flanking the terminator loci is described. Sources and types of genetic variation in bacteria are listed, from simple single nucleotide mutations to intragenic and intergenic recombinations. A model depicting the dynamics of the evolution and genetic activity of the bacterial chromosome is described which entails acquisition by recombination of clonal segments within the chromosome. The model is consistent with the existence of only a few genetic types of E. coli worldwide. Finally, there is a summary of recent reports on lateral genetic exchange across great taxonomic distances, yet another source of genetic variation and innovation.

Bacteria↗
PubMed1999

Population structure and dynamics of Magnaporthe grisea in the Indian Himalayas.

The population genetics of Magnaporthe grisea, the rice blast pathogen, were analyzed in a center of rice diversity (the Uttar Pradesh hills of the Indian Himalayas) using multilocus and single-, or low-copy, DNA markers. Based on DNA fingerprinting with the multilocus probe MGR586 and single-locus probes, 157 haplotypes clustered into 56 lineages (at >/=70% MGR586 band similarity, each with unique single-locus profiles) and high diversity indices were detected among 458 isolates collected from 29 sites during 1992-1995. Most valleys sampled had distinct populations (73% of the lineages were site specific) with some containing one or a few lineages, confirming the importance of clonal propagation, and others were very diverse. Widely distributed lineages suggested that migration occurs across the region and into the Indo-Gangetic plains. Repeated sampling at one site, Matli, (170 isolates, 1992-1995) yielded 19 lineages and diversity significantly greater than that reported from similar samples from Colombia and the Philippines. Analysis of allelic associations using pairwise comparisons and multilocus variance analysis failed to reject the hypothesis of gametic phase equilibrium. The Matli population shifted from highly diverse in 1992 to almost complete dominance by one lineage in 1995. Such population dynamics are consistent with recombination followed by differential survival of clonal descendants of recombinant progeny. At another site, Ranichauri, population (n = 84) composition changed from 2 to 11 lineages over 2 yr and yielded additional evidence for equilibrium. Sexually fertile and hermaphrodite isolates of both mating types were recovered from rice in both Matli and Ranichauri. We demonstrate that Himalayan M. grisea populations are diverse and dynamic and conclude that the structure of some populations may be affected to some extent by sexual recombination.

Crosses, Genetic↗
PubMed2004

Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer.

Prostate cancer is still diagnosed by pathologists based on subjective assessment of altered cell and tissue structure. The cellular-level structural changes diagnostic of some forms of cancer are known to be induced by cancer genes, but the relation between specific cellular-level structural features and cancer genes has not been explored in the prostate. Two important cell structural changes in prostate cancer-nucleolar enlargement and nuclear envelope (NE) irregularity-are discussed from the perspective that they should also relate to the function of the genes active in prostate cancer. Enlargement of the nucleolus is the key diagnostic feature of high-grade prostatic intraepithelial neoplasia (PIN), an early stage that appears to be the precursor to the majority of invasive prostate cancers. Nucleolar enlargement classically is associated with increased ribosome production, and production of new ribosomes appears essential for cell-cycle progression. Several cancer genes implicated in PIN are known (in other cell types) to augment ribosome production, including c-Myc, p27, retinoblastoma, p53, and growth factors that impact on ERK signaling. However, critical review of the available information suggests that increased ribosome production per se may be insufficient to explain nucleolar enlargement in PIN, and other newer functions of nucleoli may therefore need to be invoked. NE irregularity develops later in the clonal evolution of some prostate cancers, and it has adverse prognostic significance. Nuclear irregularity has recently been shown to develop dynamically during interphase following oncogene expression, without a requirement for post-mitotic NE reassembly. NE irregularity characteristic of some aggressive prostate cancers could reflect cytoskeletal forces exerted on the NE during active cell locomotion. NE irregularity could also promote chromosomal instability because it leads to chromosomal asymmetry in metaphase. Finally, NE irregularity could impact replication competence, transcriptional programming and nuclear pore function.

Biological Evolution↗
PubMed1999

Continuous in vitro propagation and differentiation of cultures of the intramolluscan stages of the human parasite Schistosoma mansoni.

The metazoan parasitic blood flukes, Schistosoma spp., infect over 200 million people worldwide and cause extensive human morbidity and mortality. Research strategies for development of anti-schistosomal agents are impeded by the organism's complex molluscan-mammalian life cycle, which limits experimental approaches and availability of material. We derived long-term continuously proliferative cultures of Schistosoma mansoni sporocysts capable of generating cercariae in vitro. Cultured organisms retained the ability to parasitize the host, and they exhibited developmental regulation of candidate stage-specific genes in the host-free culture system. Evidence for expression of a reverse transcriptase also was found in the cultured organisms, pointing to this activity as a possible mechanistic contributor to the dynamic relationship between the parasite and its hosts. Continuous in vitro propagation of the asexual sporocyst stage allows isolation of clonally derived parasite populations and provides a means to study schistosomal molecular genetics, metabolism, and evasion of host defenses.

Animals↗
PubMed1996

Evolution of fitness in experimental populations of vesicular stomatitis virus.

The evolution of fitness in experimental clonal populations of vesicular stomatitis virus (VSV) has been compared under different genetic (fitness of initial clone) and demographic (population dynamics) regimes. In spite of the high genetic heterogeneity among replicates within experiments, there is a clear effect of population dynamics on the evolution of fitness. Those populations that went through strong periodic bottlenecks showed a decreased fitness in competition experiments with wild type. Conversely, mutant populations that were transferred under the dynamics of continuous population expansions increased their fitness when compared with the same wild type. The magnitude of the observed effect depended on the fitness of the original viral clone. Thus, high fitness clones showed a larger reduction in fitness than low fitness clones under dynamics with included periodic bottleneck. In contrast, the gain in fitness was larger the lower the initial fitness of the viral clone. The quantitative genetic analysis of the trait "fitness" in the resulting populations shows that genetic variation for the trait is positively correlated with the magnitude of the change in the same trait. The results are interpreted in terms of the operation of Muller's ratchet and genetic drift as opposed to the appearance of beneficial mutations.

Adaptation, Physiological↗
PubMed2002

The structural nature of chromosomal instability in colon cancer cells.

Biological and genetic cell heterogeneity is a landmark of most colorectal cancers and provides a frame for tumor progression as an evolutional process. Classical models have hypothesized that increased genetic instability may contribute to modulating and shaping malignant transformation. This is true for the small subset of colorectal cancers displaying microsatellite instability. For the rest of colorectal tumors, numerical and/or structural chromosomal alterations are the most prominent outcome of genetic disruption. These observations have prompted some investigators to hypothesize about the presence of chromosomal instability in these cells. To characterize chromosomal instability in cancer cells, we have analyzed genetic clonal divergence in three colorectal cancer cell lines considered to be archetypes in cancer research (HCT116, LoVo, and SW480). A dynamic setting was designed to allow the calculation of mutation rates. Comprehensive analyses at the chromosomal level revealed distinctive patterns of genetic divergence. Aneuploid SW480 cells displayed high rates of structural alterations (>100-fold) as compared with near diploid LoVo cells. Numerical alterations also occurred more frequently in SW480 cells but at low rates as compared with rearrangements in the chromosomically unstable SW480 cells. These results strengthen the role of structural instability in the generation of genetic heterogeneity in colorectal cancer.

Chromosome Aberrations↗