SEARCH · PubMed Health

Results for “evolutionary scale model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1999

(R)evolutionary considerations in hematopoietic development.

Evolutionary aspects of three characteristics of the mammalian hematopoietic system are considered in the context of both established and recent data. First, the lineage relationships among early members of the hematopoietic hierarchy are reconsidered in a tripartite model proposing lineage segregation based on vascular function, innate immunity, and acquired immunity on an evolutionary time scale. Second, the observation of two stem cell populations that differ in cell cycle status is considered as an evolved mechanism to enhance survival of the species in response to exposure to environmental toxins. Finally, the mobilization of hematopoietic stem cells into the peripheral circulation is proposed to be a mechanism for rapid dissemination of myeloid function during acute bacterial infections. These revolutionary hypotheses challenge some conventional concepts of stem cell biology, and provide an evolutionary context for considering mammalian hematopoiesis.

Animals↗

PubMed2006

Topology of resultant networks shaped by evolutionary pressure.

Understanding the topology of complex systems abstracted to networks is important for unraveling their functional capabilities. Many such networks follow the small-world and scale-free regimes. Several models of artificially growing networks lead to this observed network topology. Most previously proposed models for growing networks, such as rich-get-richer and duplication-divergence, produce realistic network topologies but do not consider the effects of exogenous forces such as optimization for adaptation in shaping network topology. It is likely that such forces have shaped complex systems throughout their evolution. To develop further insights into possible mechanisms that shape networks, a model that uses several previously proposed network growth algorithms was developed to grow networks that adapt under exogenous stress. A decision tree problem was used to generate a complex Boolean function. Growing networks were required to adapt to correctly decode this function using an evolutionary selection process. Under this growth regimen all growing network models are similarly adaptable. The newly added nodes tend to cluster into pathways emanating from few inputs, regardless of the growth algorithm. Distribution of redundant pathways from inputs to the output follow a power-law function with a scaling exponent (approximately 1.3). Similar distribution of redundant pathways was observed from inputs in a cell signaling network and an air traffic control network. A flat distribution of redundant pathways from inputs was observed in growing networks that do not attempt to adapt. This analysis provides initial insights into distribution of pathways in naturally evolving complex systems that have defined input-output relationships.

Algorithms↗

PubMed2003

Description and interpretation of adaptive evolution of Escherichia coli K-12 MG1655 by using a genome-scale in silico metabolic model.

Genome-scale in silico metabolic networks of Escherichia coli have been reconstructed. By using a constraint-based in silico model of a reconstructed network, the range of phenotypes exhibited by E. coli under different growth conditions can be computed, and optimal growth phenotypes can be predicted. We hypothesized that the end point of adaptive evolution of E. coli could be accurately described a priori by our in silico model since adaptive evolution should lead to an optimal phenotype. Adaptive evolution of E. coli during prolonged exponential growth was performed with M9 minimal medium supplemented with 2 g of alpha-ketoglutarate per liter, 2 g of lactate per liter, or 2 g of pyruvate per liter at both 30 and 37 degrees C, which produced seven distinct strains. The growth rates, substrate uptake rates, oxygen uptake rates, by-product secretion patterns, and growth rates on alternative substrates were measured for each strain as a function of evolutionary time. Three major conclusions were drawn from the experimental results. First, adaptive evolution leads to a phenotype characterized by maximized growth rates that may not correspond to the highest biomass yield. Second, metabolic phenotypes resulting from adaptive evolution can be described and predicted computationally. Third, adaptive evolution on a single substrate leads to changes in growth characteristics on other substrates that could signify parallel or opposing growth objectives. Together, the results show that genome-scale in silico metabolic models can describe the end point of adaptive evolution a priori and can be used to gain insight into the adaptive evolutionary process for E. coli.

Adaptation, Physiological↗

PubMed2005

Structure alignment via Delaunay tetrahedralization.

A novel protein structure alignment technique has been developed reducing much of the secondary and tertiary structure to a sequential representation greatly accelerating many structural computations, including alignment. Constructed from incidence relations in the Delaunay tetrahedralization, alignments of the sequential representation describe structural similarities that cannot be expressed with rigid-body superposition and complement existing techniques minimizing root-mean-squared distance through superposition. Restricting to the largest substructure superimposable by a single rigid-body transformation determines an alignment suitable for root-mean-squared distance comparisons and visualization. Restricted alignments of a test set of histones and histone-like proteins determined superpositions nearly identical to those produced by the established structure alignment routines of DaliLite and ProSup. Alignment of three, increasingly complex proteins: ferredoxin, cytidine deaminase, and carbamoyl phosphate synthetase, to themselves, demonstrated previously identified regions of self-similarity. All-against-all similarity index comparisons performed on a test set of 45 class I and class II aminoacyl-tRNA synthetases closely reproduced the results of established distance matrix methods while requiring 1/16 the time. Principal component analysis of pairwise tetrahedral decomposition similarity of 2300 molecular dynamics snapshots of tryptophanyl-tRNA synthetase revealed discrete microstates within the trajectory consistent with experimental results. The method produces results with sufficient efficiency for large-scale multiple structure alignment and is well suited to genomic and evolutionary investigations where no geometric model of similarity is known a priori.

Algorithms↗

PubMed2001

Two continuous models for the dynamics of sandpile surfaces.

We consider a modified Bouchaud-Cates-Ravi Prakash-Edwards model for pile surface dynamics, and show that in the long-scale limit this model converges to a quasistationary model of pile growth in the form of an evolutionary variational inequality.

Biophysics↗

PubMed1999

Conservatism of ecological niches in evolutionary time

Theory predicts low niche differentiation between species over evolutionary time scales, but little empirical evidence is available. Reciprocal geographic predictions based on ecological niche models of sister taxon pairs of birds, mammals, and butterflies in southern Mexico indicate niche conservatism over several million years of independent evolution (between putative sister taxon pairs) but little conservatism at the level of families. Niche conservatism over such time scales indicates that speciation takes place in geographic, not ecological, dimensions and that ecological differences evolve later.

Journal Article↗

PubMed1985

Generation of single base-pair deletions, insertions, and substitutions by a site-specific recombination system.

The sequence analysis of both products of individual phi 80 site-specific recombination events in vivo shows that recombination with a secondary attachment (att) site generates several different novel joints at the mismatched position: one recombination event resulted in a single base-pair deletion and two other recombination events resulted in two different single base-pair substitutions. The characterized products of recombination can be straightforwardly interpreted as the outcome of strand exchange involving staggered nicks bracketing the heterology within an overlap region of five to nine base pairs. In comparison, more complex segregation patterns have been observed in previous studies of lambda recombination between nonidentical att sites; the nature of the overlap region heterology may have a significant effect on the segregation patterns. To recover both products of a single recombination event, we used a plasmid that carries the phi 80 int and xis genes and both att sites. Because the two att sites are situated in opposite orientation, intramolecular recombination between them inverts rather than deletes the intervening segment of DNA. Although subsequent reinversion restores the original gross genetic arrangement, single base-pair insertions, deletions, and substitutions are introduced at the sites of recombination. One of the mutations improves the recombination efficiency of the secondary att site and thereby converts a formerly "stable" sequence to an efficient target for rearrangement, and other mutations are predicted to alter the specificity of recombination. These pathways may also provide useful models for the efficient generation of localized sequence diversity on a development (as well as evolutionary) time scale.

Bacteriophage lambda↗

PubMed2026

A pangenome framework uncovers the role of deletions in repeated evolution of cave-derived traits.

Structural variants (SVs) are increasingly recognized as key contributors to adaptive evolution, yet they remain underexplored compared with single-nucleotide variation. To understand how large-scale genomic changes shape repeated evolution, we leveraged multiple levels of sequence data across the powerful evolutionary model system of the Mexican tetra fish (Astyanax mexicanus). We constructed one of the first pangenome graphs from a naturally evolving vertebrate, enabling comprehensive discovery of SVs among 120 fish from 11 populations. We discover substantial amounts of structural variation and explore the roles of genomic biases and selection in shaping the distribution of these variants. More than 2400 high-confidence cave-specific deletions are enriched in biological pathways involved in vision, metabolism, and behavior and cluster nonrandomly in quantitative trait loci linked to cavefish traits. Additionally, 67 genes harbor unique deletions between independent cavefish lineages. These reused genes show evidence of population-specific selection (99% contain selective sweeps compared with 8%-15% in genes lacking SVs), indicating that deletions likely rose in frequency through repeated positive selection rather than drift. Together, these results reveal that recurrent deletion events have repeatedly contributed to the evolution of cave-adapted phenotypes and highlight deletions as underexplored contributors of adaptive evolution in extreme environments.

Animals↗

PubMed1993

Epidemiology of contagious diseases, ecology of mammals, health, management and conservation biology: concluding remarks.

In conclusion to the Proceedings of the Symposium on the Health and management of free-ranging mammals (held in Nancy, France, in 1991), the author presents a review of the literature on the ecology of diseases of wild mammals. This discipline involves the ecology of both pathogens and hosts. The ecology of a pathogen may be considered as a synonym of epidemiology, i.e. the mode of transmission and circulation of parasites, their origin, invasion and persistence. The ecology of the host deals with the outcome of infection within different geographical and time scales: a) the impact on population density and communities within the time scale of the "observer" b) the effect of infection on the co-evolution of hosts and pathogens within the evolutionary time scale. This account is illustrated by numerous examples from field studies, as well as mathematical models, and concludes by examining the effect of pathogens on biodiversity, human health and the health of domestic animals.

Animals↗

PubMed2000

[Genetic evolution under vaccine pressure: the Bordetella pertussis model].

A possible genetic selective pressure related to the long-term use of vaccines has been the object of recent theoretical thought and publications. For more than thirty years, an effective vaccine has been in use against whooping cough on a wide scale basis in several countries. Thus, the Bordetella pertussis model may contribute to the analysis of an evolutionary risk linked to the vaccine. To maintain and improve the control of whooping cough, better vaccination coverage must be achieved in countries where prevalence is low. In countries where high vaccination coverage has been achieved over a long period, a trend toward the resurgence of the disease has been observed. Efforts are therefore now being directed toward primary vaccination and boosters. These two targets require new vaccines with fewer side effects. Outbreaks in highly vaccinated populations have been reported, raising the issues of vaccine efficacy, of the long-term effect of vaccines on the transmission of the disease, and of genetic selective pressure. Time trend modifications of circulating strains related to vaccination practices and vaccine types have been observed and are compatible with a selective pressure of the vaccine on related pathogens. However, evidence for a causal relation is lacking. In order to monitor and understand the various effects the vaccine may be having on the effectiveness of immunisation against whooping cough, further surveillance is needed, integrating a standardised characterisation of circulating strains and vaccines by way of a space-time sampling model.

Biological Evolution↗

PubMed1998

Genetic measurement of theory of epistatic effects.

Epistasis is defined as the influence of the genotype at one locus on the effect of a mutation at another locus. As such it plays a crucial role in a variety of evolutionary phenomena such as speciation, population bottle necks, and the evolution of genetic architecture (i.e., the evolution of dominance, canalization, and genetic correlations). In mathematical population genetics, however, epistasis is often represented as a mere noise term in an additive model of gene effects. In this paper it is argued that epistasis needs to be scaled in a way that is more directly related to the mechanisms of evolutionary change. A review of general measurement theory shows that the scaling of a quantitative concept has to reflect the empirical relationships among the objects. To apply these ideas to epistatic mutation effects, it is proposed to scale A x A epistatic effects as the change in the magnitude of the additive effect of a mutation at one locus due to a mutation at a second locus. It is shown that the absolute change in the additive effect at locus A due to a substitution at locus B is always identical to the absolute change in B due to the substitution at A. The absolute A x A epistatic effects of A on B and of B on A are identical, even if the relative effects can be different. The proposed scaling of A x A epistasis leads to particularly simple equations for the decomposition of genotypic variance. The Kacser Burns model of metabolic flux is analyzed for the presence of epistatic effects on flux. It is shown that the non-linearity of the Kacser Burns model is not sufficient to cause A x A epistasis among the genes coding for enzymes. It is concluded that non-linearity of the genotype-phenotype map is not sufficient to cause epistasis. Finally, it is shown that there exist correlations among the additive and epistatic effects among pairs of loci, caused by the inherent symmetries of Mendelian genetic systems. For instance, it is shown that a mutation that has a larger than average additive effect will tend to decrease the additive effect of a second mutation, i.e., it will tend to have a negative (canalizing) interaction with a subsequent gene substitution. This is confirmed in a preliminary analysis of QTL-data for adult body weight in mice.

Animals↗

PubMed2003

Numerical bifurcation analysis of ecosystems in a spatially homogeneous environment.

The dynamics of single populations up to ecosystems, are often described by one or a set of non-linear ordinary differential equations. In this paper we review the use of bifurcation theory to analyse these non-linear dynamical systems. Bifurcation analysis gives regimes in the parameter space with quantitatively different asymptotic dynamic behaviour of the system. In small-scale systems the underlying models for the populations and their interaction are simple Lotka-Volterra models or more elaborated models with more biological detail. The latter ones are more difficult to analyse, especially when the number of populations is large. Therefore for large-scale systems the Lotka-Volterra equations are still popular despite the limited realism. Various approaches are discussed in which the different time-scale of ecological and evolutionary biological processes are considered together.

Animals↗

PubMed1989

Towards an artificial brain.

Three components of a brain model operating on neuromolecular computing principles are described. The first component comprises neurons whose input-output behavior is controlled by significant internal dynamics. Models of discrete enzymatic neurons, reaction-diffusion neurons operating on the basis of the cyclic nucleotide cascade, and neurons controlled by cytoskeletal dynamics are described. The second component of the model is an evolutionary learning algorithm which is used to mold the behavior of enzyme-driven neurons or small networks of these neurons for specific function, usually pattern recognition or target seeking tasks. The evolutionary learning algorithm may be interpreted either as representing the mechanism of variation and natural selection acting on a phylogenetic time scale, or as a conceivable ontogenetic adaptation mechanism. The third component of the model is a memory manipulation scheme, called the reference neuron scheme. In principle it is capable of orchestrating a repertoire of enzyme-driven neurons for coherent function. The existing implementations, however, utilize simple neurons without internal dynamics. Spatial navigation and simple game playing (using tic-tac-toe) provide the task environments that have been used to study the properties of the reference neuron model. A memory-based evolutionary learning algorithm has been developed that can assign credit to the individual neurons in a network. It has been run on standard benchmark tasks, and appears to be quite effective both for conventional neural nets and for networks of discrete enzymatic neurons. The models have the character of artificial worlds in that they map the hierarchy of processes in the brain (at the molecular, neuronal, and network levels), provide a task environment, and use this relatively self-contained setup to develop and evaluate learning and adaptation algorithms.

Artificial Intelligence↗

PubMed1994

Cell-lytic and antibacterial peptides that act by perturbing the barrier function of membranes: facets of their conformational features, structure-function correlations and membrane-perturbing abilities.

Almost all hemolytic and antimicrobial peptides form part of the defense mechanism of species widely distributed across the evolutionary scale. Although these peptides are of varying lengths and composition, they form amphiphilic structures in a hydrophobic environment. They also have the ability to form channels in natural and model membranes. Hemolytic peptides have proven to be very useful in studying the mechanism of hemolysis and the permeability properties of red blood cells. Preliminary investigations indicate that these peptides may also be useful in the investigation of complex cellular phenomena like exocytosis and neurotransmission. Although molecules like vancomycin, bacitracin and penicillins have been extensively used as antibiotics for therapeutic purposes, most species throughout the evolutionary scale use peptides as antimicrobial agents. These peptides exert their activity by altering the permeability properties of the bacterial plasma membrane and do not interfere with macro molecular synthesis like the other antibiotics that are presently used in therapies. Hence it is likely that resistance to peptide antibacterial agents may not develop easily. Since the problem of antibiotic resistance is presently a particularly severe one, peptide antibiotics may be the drugs of choice in the future.

Amino Acid Sequence↗

PubMed2003

Evolutionary pace of chromosomal polymorphism in colonizing populations of Drosophila subobscura: an evolutionary time series.

Biologists have long debated the speed, uniformity, and predictability of evolutionary change. However, evaluating such patterns on a geographic scale requires time-series data on replicate sets of natural populations. Drosophila subobscura has proven an ideal model system for such studies. This fly is broadly distributed in the Old World, but was introduced into both North and South America just over two decades ago and then spread rapidly. Rapid, uniform, and predictable evolution would be demonstrated if the invading flies evolved latitudinal clines that progressively converged on those of the native populations. Evolutionary geneticists quickly capitalized on this opportunity to monitor evolutionary dynamics. Just a few years after the introduction, they surveyed chromosomal inversion frequencies in both North and South America. On both continents they detected incipient latitudinal clines in chromosome inversion frequencies that almost always had the same sign with latitude as in the Old World. Thus the initial evolution of chromosomal polymorphisms on a continental scale was remarkably rapid and consistent. Here we report newer samples of inversion frequencies for the colonizing populations: the time series now spans almost one decade for North America and almost two decades for South America. Almost all inversions in the New World continue to show the same sign of frequency with latitude as in the Old World. Nevertheless, inversion clines have not consistently increased in steepness over time; nor have they consistently continued to converge on the Old World baseline. However, five arrangements in South America show directional, continentwide shifts in frequency. Overall, the initial consistency of clinal evolutionary trajectories seen in the first surveys seems not to have been maintained.

Animals↗

PubMed2001

Hormesis: a generalizable and unifying hypothesis.

The present article represents a comprehensive effort to assess the hypothesis that hormesis is a highly generalizable biological phenomenon independent of environmental stressor, biological endpoint, and experimental model system. The evaluative methodology and complementary approaches employed to assess this question are (1) evolutionary biology-based theoretical paradigm; (2) evaluation of > 20,000 toxicology articles using a priori entry and evaluative criteria; (3) evaluation of 17 large-scale studies each providing data on numerous agents tested in the same experimental model by the same research team; (4) the assimilation of experimental pharmacological data on 24 receptor systems in which biphasic dose responses have been established reproducibly along with hormetic mechanism elucidation; and (5) assessment of the original hormesis database with 1600 dose-response relationships demonstrating evidence consistent with the hormesis hypothesis. The complementary approaches for assessing hormesis provided strong support for its credibility as a central biological theory based on its high frequency of occurrence and quantitative features of expression within microbe, plant, and invertebrate and vertebrate animal systems. The findings suggest that hormetic effects represent evolutionary-based adaptive responses to environmentally induced disruptions in homeostasis. Such adaptive responses, which are incorporated into organismal integrative physiological systems and now clarified at the mechanistic level for more than two dozen receptor systems, provide a cogent basis for the application of hormetic mechanisms in the elucidation of fundamental evolutionary-based biological processes and in the development of novel clinical modalities.

Adaptation, Physiological↗

PubMed2005

Evolutionary programming as a platform for in silico metabolic engineering.

BACKGROUND: Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms where structural and stoichiometric complexity is inherently accounted for. New algorithms are being developed by using genome-scale metabolic models that enable identification of gene knockout strategies for obtaining improved phenotypes. However, the problem of finding optimal gene deletion strategy is combinatorial and consequently the computational time increases exponentially with the size of the problem, and it is therefore interesting to develop new faster algorithms. RESULTS: In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters in industrial fermentations, one linear and other non-linear, by using a genome-scale model of the yeast Saccharomyces cerevisiae. Potential metabolic engineering targets for improved production of succinic acid, glycerol and vanillin are identified and underlying flux changes for the predicted mutants are discussed. CONCLUSION: We show that evolutionary programming enables solving large gene knockout problems in relatively short computational time. The proposed algorithm also allows the optimization of non-linear objective functions or incorporation of non-linear constraints and additionally provides a family of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span several different pathways and may be necessary for solving challenging metabolic engineering problems.

Algorithms↗

PubMed2004

Fine-scale geographical structure, intra-individual polymorphism and recombination in nuclear ribosomal internal transcribed spacers in Armeria (Plumbaginaceae).

BACKGROUND AND AIMS: Isolation and drift are the main causes for geographic structure of molecular variation. In contrast, the one found in a previous survey in Armeria (Plumbaginaceae) for nuclear ribosomal ITS multicopy regions was species-independent and has been hypothesized to be due to extensive gene-flow and biased concerted evolution. Since this was inferred from a genus-level phylogenetic analysis, the aim of this study was to check for the occurrence of such structure and the validity of the proposed model at a local scale, in a southern Spanish massif (Sierra Nevada), as well as to examine the evolutionary implications at the organism level. METHODS: In addition to 117 sequences of direct PCR products from genomic DNA, 50 sequences of PCR products from cloned DNA were obtained to analyse cases of intragenomic polymorphisms for the ITS regions. KEY RESULTS: Sequence data confirm the occurrence of a species-independent structure at a local scale and reveal insights through the analysis of contact areas between different ITS copies (ribotypes). A comparison between cloned and direct sequences (a) confirms that, within these contact areas, ITS copies co-occur both in different individuals and within single genomes; and (b) reveals recombination between different copies. CONCLUSIONS: This study supports the utility of direct sequences for detecting intra-individual polymorphism and for partially inferring the ITS copies involved, given previous knowledge of the variability. The main evolutionary implication at the organism level is that gene-flow and concerted evolution shape the geographic structure of ITS variation.

Base Sequence↗