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PubMed2003

Bivariate longitudinal model for the analysis of the evolution of HIV RNA and CD4 cell count in HIV infection taking into account left censoring of HIV RNA measures.

We present a bivariate linear mixed model taking into account censored measures of the response variable due to lower quantification limit of the assays. It allows an estimate of the correlation between the two response variables and takes into account this correlation for the estimation of other model parameters. This model was applied in a large cohort study (APROCO Cohort) to study the evolution under antiretroviral treatment of the two major biomarkers of the progression of Human Immunodeficiency Virus (HIV) infection: plasma HIV RNA and CD4+ T lymphocytes cell count. In a sample of 929 patients who started an highly active antiretroviral therapy, we illustrate the superiority in terms of likelihood of a bivariate model compared to two univariate models and the impact of taking into account the left-censoring of HIV-RNA. Moreover, interpretation of the model parameters allows confirmation of correlation between these two markers throughout the whole follow-up and the continuous decrease of plasma HIV RNA on average. Despite some limitations (distribution assumption, ignorance of missingness process), such a model appeared to be very useful to correctly describe the current evolution of important biomarkers in HIV infection.

CD4 Lymphocyte Count↗

PubMed1988

Arachidonate metabolism in myocardial ischemia and reperfusion.

Circulatory blood corpuscles have enzymes catalyzing arachidonic acid. Platelets have cyclo-oxygenase system which produce highly vasoconstrictive and thrombogenic thromboxane A2 (TXA2). Neutrophils have another type of arachidonate metabolism system, lipoxygenase enzymes, which produce hydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT), mediating inflammatory reactions. These arachidonate metabolites were found to play important roles in the evolution of myocardial ischemia. Thromboxane B2 (TXB2) a stable metabolite of TXA2, was elevated in peripheral blood of patients with angina pectoris. This elevation of TXB2 was supposed to be derived from platelet activation in coronary circulation due to altered production of TXA2 and prostacyclin (PGI2). Augmentation of TXA2 was also observed in patients with acute myocardial infarction. TXA2 synthetase inhibitors decreased plasma levels of TXB2 in these patients accompanied by attenuation of infarct size. Neutrophils were found to accumulate in ischemic myocardium and were augmented at reperfusion phase especially at interface between infarcted and risk zone. These infiltrated neutrophils may also provide deleterious effects on myocardial cells by producing lipoxygenase metabolites. In fact, a chemotactic and vasoconstrictive lipoxygenase product, 12-HETE, was produced selectively in ischemic myocardial tissue of an occlusion-reperfusion model. During evolution of myocardial cell damage, platelets and neutrophils, accumulated in ischemic tissue, may contribute to the exacerbation of microcirculatory disorders by producing vasoactive prostanoids, leading to expansion of myocardial necrosis. We should gain insights into these cellular interactions through arachidonate metabolism under normal and catastrophic conditions of coronary circulation.

Arachidonic Acids↗

PubMed2003

The evolutionary history of Shigella and enteroinvasive Escherichia coli revised.

In Shigella and enteroinvasive Escherichia coli (EIEC), the etiologic agents of shigellosis in humans, the determinants responsible for entry of bacteria into and dissemination within epithelial cells are encoded by a virulence plasmid. To understand the evolution of the association between the virulence plasmid and the chromosome, we performed a phylogenetic analysis using the sequences of four chromosomal genes (trpA, trpB, pabB, and putP) and three virulence plasmid genes (ipaB, ipaD, and icsA) of a collection of 51 Shigella and EIEC strains. The phylogenetic tree derived from chromosomal genes showed a typical "star" phylogeny, indicating a fast diversification of Shigella and EIEC groups. Phylogenetic groups obtained from the chromosomal and plasmidic genes were similar, suggesting that the virulence plasmid and the chromosome share similar evolutionary histories. The few incongruences between the trees could be attributed to exchanges of fragments of different plasmids and not to the transfer of an entire plasmid. This indicates that the virulence plasmid was not transferred between the different Shigella and EIEC groups. These data support a model of evolution in which the acquisition of the virulence plasmid in an ancestral E. coli strain preceded the diversification by radiation of all Shigella and EIEC groups, which led to highly diversified but highly specialized pathogenic groups.

Base Sequence↗

PubMed2002

The coevolution of warning signals.

It has long been recognized that defended prey tend to be conspicuous. Current theories suggest that the association ('aposematism') has arisen because predators more readily learn to avoid attacking defended phenotypes when they are conspicuous. In this paper, I consider why such psychology has evolved. In particular, I argue that aposematism may have evolved not because of an independent and pre-existing receiver bias, but because the conspicuousness of a prey item provides a reliable indicator of its likelihood of being defended. To develop my case I consider how warning signals might coevolve in a system containing a number of predators, whose foraging behaviour is also subject to selection. In these cases, models readily show that the greater the conspicuousness of a novel prey item, the more likely that it has been encountered by other predators and survived. As a consequence, naive predators should be less likely to attack highly conspicuous novel prey on encounter, or at least more inclined to attack them cautiously. This adaptive predator behaviour will greatly facilitate the spread of aposematic phenotypes from extreme rarity, which in turn will enhance selection for forms of predator behaviour under which aposematism will coevolve even more readily.

Animals↗

PubMed2000

Isomorphism of quasispecies and percolation models.

Population dynamics of tRNA-like macromolecules and viruses have been interpreted by Eigen (1971, Naturwissenschaften58, 465-526) on the basis of the "quasispecies" model. The present paper contains a qualitative analysis of the similarities between Eigen's quasispecies model and percolation models. In fact, different phenomena characterized by an analogous inner structure can conceivably be described by quite similar mathematical formalisms. The occurrence of a threshold in specific processes predicted by the models is considered first. Secondly, Ising's model of ferromagnetism is taken into account in the last section. An interpretation of the above-mentioned biological theory in terms of percolation, implying a zeroth-order approximation to the real situation, might be a point of departure to a deeper insight obtainable with more refined approaches. A better comprehension of biological phenomena might in any case arise from a percolative approach, even if the description of the systems is simplified. An overview of some quasispecies results and some plausible applications are presented.

Biological Evolution↗

PubMed2002

Chloroplast phylogeography and evolution of highly polymorphic microsatellites in lodgepole pine ( Pinus contorta).

We employed a novel set of six highly polymophic chloroplastic simple sequence repeat (cpSSR) loci to investigate the phylogeography of lodgepole pine ( Pinus contorta Dougl. Ex. Loud.), and to examine aspects of the evolutionary process operating on these repetitive DNA sequences. Chloroplast haplotypes of 500 trees, sampled throughout the range of lodgepole pine, were determined. We found a marked association of genetic distance with physical distance within the scale of 0 to 1,000 km, but no association beyond that range. Likewise, geographic clustering was observed only among recent clades in a dendrogram. These phylogeographic patterns are consistant with a rapid rangewide expansion ("big-bang") followed by recent, local population differentiation ("galaxy formation"). In support of this expansion, coalescent simulations of the genealogical process gave a long-term effective population size in the low thousands, and a time to common ancestry of about 1,500 generations (12,000 years), consistent with a post-Pleistocene population expansion as documented by previous pollen-sediment analyses. Two lines of evidence (mapping mutational events onto a phylogeny, and evaluation of observed versus expected gene diversity) suggest that five of the cpSSR loci evolve primarily by a stepwise model of evolution of single repeat changes (but with a small proportion of changes involving two or more repeats), and the coalescent simulations point to a mutation rate of about 10(-3).

Journal Article↗

PubMed1994

Analysis of peptides from known proteins: clusterization in sequence space.

A combinatorial sequence space (CSS) model was introduced to represent sequences as a set of overlapping k-tuples of some fixed length which correspond to points in the CSS. The aim was to analyze clusterization of protein sequences in the CSS and to test various hypotheses about the possible evolutionary basis of this clusterization. The authors developed an easy-to-use technique which can reveal and analyze such a clusterization in a multidimensional CSS. Application of the technique led to an unexpectedly high clusterization of points in the CSS corresponding to k-tuples from known proteins. The clusterization could not be inferred from nonuniform amino acid frequencies or be explained by the influence of homologous data. None of the tested possible evolutionary and structural factors could explain the clusterization observed either. It looked as if certain protein sequence variations occurred and were fixed in the early course of evolution. Subsequent evolution (predominantly neutral) allowed only a limited number of changes and permitted new variants which led to preservation of certain k-tuples during the course of evolution. This was consistent with the theory of exon shuffling and protein block structure evolution. Possible applications of sequence space features found were also discussed.

Biological Evolution↗

PubMed2006

Unifying the theories of inclusive fitness and reciprocal altruism.

Inclusive fitness and reciprocal altruism are widely thought to be distinct explanations for how altruism evolves. Here we show that they rely on the same underlying mechanism. We demonstrate this commonality by applying Hamilton's rule, normally associated with inclusive fitness, to two simple models of reciprocal altruism: one, an iterated prisoner's dilemma model with conditional behavior; the other, a mutualistic symbiosis model where two interacting species differ in conditional behaviors, fitness benefits, and costs. We employ Queller's generalization of Hamilton's rule because the traditional version of this rule does not apply when genotype and phenotype frequencies differ or when fitness effects are nonadditive, both of which are true in classic models of reciprocal altruism. Queller's equation is more general in that it applies to all situations covered by earlier versions of Hamilton's rule but also handles nonadditivity, conditional behavior, and lack of genetic similarity between altruists and recipients. Our results suggest changes to standard interpretations of Hamilton's rule that focus on kinship and indirect fitness. Despite being more than 20 years old, Queller's generalization of Hamilton's rule is not sufficiently appreciated, especially its implications for the unification of the theories of inclusive fitness and reciprocal altruism.

Altruism↗

PubMed2002

Chromosomal rearrangements and evolution of recombination: comparison of chiasma distribution patterns in standard and robertsonian populations of the house mouse.

The effects of chromosomal rearrangements on recombination rates were tested by the analysis of chiasma distribution patterns in wild house mice. Males and females of two chromosomal races from Tunisia differing by nine pairs of Robertsonian (Rb) fusions (standard all-acrocentric, 2N = 40 and 2N = 22) were studied. A significant decrease in chiasma number (CN) was observed in Rb mice compared to standard ones for both sexes. The difference in CN was due to a reduction in the number of proximal chiasmata and was associated with an overall more distal redistribution. These features were related to distance of chiasmata to the centromere, suggesting that the centromere effect was more pronounced in Rb fusions than in acrocentric chromosomes. These modifications were interpreted in terms of structural meiotic constraints, although genic factors were likely involved in patterning the observed differences between sexes within races. Thus, the change in chromosomal structure in Rb mice was associated with a generalized decrease in recombination due to a reduction in diploid number, a lower CN, and a decrease in the efficiency of recombination. The effects of such modifications on patterns of genic diversity are discussed in the light of models of evolution of recombination.

Animals↗

PubMed1989

Saltatory transitions are a naturally occurring property of evolving systems.

On the basis of paleological evidence, it has been suggested that biological evolution need not necessarily be characterized by gradual change. Rather, evolutionary history may display saltatory periods of rapid speciation alternating with periods of relative quiescence, the whole dynamic being called punctuated equilibria. The empirical evidence that has been presented in support of this hypothesis has been the object of a vigorous dispute. Mathematical investigations of complex models of biological evolution that contain random elements have demonstrated that these systems can display saltatory behavior. In this paper we address a more abstract question: can saltations occur in the evolution of very simple, deterministic mathematical systems that function in a constant environment? The answer appears to be yes. Saltations appear as a natural dynamical behavior in the evolution of simplistic information processing networks. We stress that these networks do not constitute a model of biological evolution. However, the appearance of saltations in such simple systems suggests that their appearance in a process as complex as biological evolution is not surprising.

Animals↗

PubMed1994

Structure of the gene encoding the alpha subunit of the human granulocyte-macrophage colony stimulating factor receptor. Implications for the evolution of the cytokine receptor superfamily.

The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of at least two subunits, alpha and beta. In addition to the conserved cysteine residues and a "WSxWS" motif, the extracellular segments of both subunits have domains that are structurally related to a fibronectin type III domain. This structure is conserved in all members of the cytokine receptor superfamily. We isolated and characterized genomic DNA clones containing the entire coding sequences of the alpha subunit of the human GM-CSF receptor (hGMR alpha). The gene spans approximately 44 kilobases and has 13 exons. The major transcription initiation site was determined to be 195 base pairs upstream of the translation initiation site. The putative promoter region lacks a typical TATA motif and an Sp1 binding site, but contains a purine-rich stretch about 30 base pairs upstream of the transcription initiation site. This stretch is also found in the human interleukin 2 receptor gamma subunit and granulocyte colony-stimulating factor receptor genes. We compared the exon-intron organization of the hGMR alpha gene with other members of the cytokine receptor superfamily and found the genomic organizations to be remarkably well conserved. On the basis of these observations, we propose a model for evolution of this gene family.

Base Sequence↗

PubMed2001

Evolution of reduced dispersal mortality and 'fat-tailed' dispersal kernels in autocorrelated landscapes.

Models describing the evolution of dispersal strategies have mostly focused on the evolution of dispersal rates. Taking trees as a model for organisms with undirected, passive dispersal, we have developed an individual-based, spatially explicit simulation tool to investigate the evolution of the dispersal kernel, P(r), and its resulting cumulative seed-density distribution, D(r). Simulations were run on a variety of fractal landscapes differing in the fraction of suitable habitat and the spatial autocorrelation. Starting from a uniform D(r), evolution led to an increase in the fraction of seeds staying in the home cell, a reduction of the dispersal mortality (arrival in unsuitable habitat), and the evolution of 'fat-tailed' D(r) in autocorrelated landscapes and approximately uniform D(r) in random landscapes. The evolutionary process was characterized by long periods of stasis with a few bouts of rapid change in the dispersal rate.

Biological Evolution↗

PubMed2002

Removal of As, Mn, Mo, Se, U, V and Zn from groundwater by zero-valent iron in a passive treatment cell: reaction progress modeling.

Three treatment cells were operated at a site near Durango, CO. One treatment cell operated for more than 3 years. The treatment cells were used for passive removal of contamination from groundwater at a uranium mill tailings repository site. Zero-valent iron [Fe(0)] that had been powdered, bound with aluminosilicate and molded into plates was used as a reactive material in one treatment cell. The others used granular Fe(0) and steel wool. The treatment cells significantly reduced concentrations of As, Mn, Mo, Se, U, V and Zn in groundwater that flowed through it. Zero-valent iron [Fe(0)], magnetite (Fe3O4), calcite (CaCO3), goethite (FeOOH) and mixtures of contaminant-bearing phases were identified in the solid fraction of one treatment cell. A reaction progress approach was used to model chemical evolution of water chemistry as it reacted with the Fe(0). Precipitation of calcite, ferrous hydroxide [Fe(OH)2] and ferrous sulfide (FeS) were used to simulate observed changes in major-ion aqueous chemistry. The amount of reaction progress differed for each treatment cell. Changes in contaminant concentrations were consistent with precipitation of reduced oxides (UO2, V2O3), sulfides (As2S3, ZnS), iron minerals (FeSe2, FeMoO4) and carbonate (MnCO3). Formation of a free gas phase and precipitation of minerals contributed to loss of hydraulic conductivity in one treatment cell.

Arsenic↗

PubMed2001

Coexistence under positive frequency dependence.

Negative frequency dependence resulting from interspecific interactions is considered a driving force in allowing the coexistence of competitors. While interactions between species and genotypes can also result in positive frequency dependence, positive frequency dependence has usually been credited with hastening the extinction of rare types and is not thought to contribute to coexistence. In the present paper, we develop a stochastic cellular automata model that allows us to vary the scale of frequency dependence and the scale of dispersal. The results of this model indicate that positive frequency dependence will allow the coexistence of two species at a greater rate than would be expected from chance. This coexistence arises from the generation of banding patterns that will be stable over long time-periods. As a result, we found that positive frequency-dependent interactions over local spatial scales promote coexistence over neutral interactions. This result was robust to variation in boundary conditions within the simulation and to variation in levels of disturbance. Under all conditions, coexistence is enhanced as the strength of positive frequency-dependent interactions is increased.

Animals↗

PubMed2006

The narrow-leaf syndrome: a functional and evolutionary approach to the form of fog-harvesting rosette plants.

Plants that use fog as an important water-source frequently have a rosette growth habit. The performance of this morphology in relation to fog interception has not been studied. Some first-principles from physics predict that narrow leaves, together with other ancillary traits (large number and high flexibility of leaves, caudices, and/or epiphytism) which constitute the "narrow-leaf syndrome" should increase fog-interception efficiency. This was tested using aluminum models of rosettes that differed in leaf length, width and number and were exposed to artificial fog. The results were validated using seven species of Tillandsia and four species of xerophytic rosettes. The total amount of fog intercepted in rosette plants increased with total leaf area, while narrow leaves maximized interception efficiency (measured as interception per unit area). The number of leaves in the rosettes is physically constrained because wide-leafed plants can only have a few blades. At the limits of this constraint, net fog interception was independent of leaf form, but interception efficiency was maximized by large numbers of narrow leaves. Atmospheric Tillandsia species show the narrow-leaf syndrome. Their fog interception efficiencies were correlated to the ones predicted from aluminum-model data. In the larger xerophytic rosette species, the interception efficiency was greatest in plants showing the narrow-leaf syndrome. The adaptation to fog-harvesting in several narrow-leaved rosettes was tested for evolutionary convergence in 30 xerophytic rosette species using a comparative method. There was a significant evolutionary tendency towards the development of the narrow-leaf syndrome the closer the species grew to areas where fog is frequently available. This study establishes convergence in a very wide group of plants encompassing genera as contrasting as Tillandsia and Agave as a result of their dependence on fog.

Aluminum↗

PubMed1984

The evolution of multigene families under intrachromosomal gene conversion.

A model for the evolution of the probabilities of genetic identity within and between loci of a multigene family in a finite population is formulated and investigated. Unbiased intrachromosomal gene conversion, equal crossing over between tandemly repeated genes, random genetic drift and mutation to new alleles are incorporated. Generations are discrete and nonoverlapping; the diploid, monoecious population mates at random. Formulas for the equilibrium values of the probabilities of identity and a cubic equation for the rate of convergence are deduced. Numerical examples indicate the following. The amount of homology at equilibrium generally decreases as the mutation rate, the population size and the number of repeats increase; it may increase or decrease with increasing crossover rate. The intralocus homology has an intermediate minimum, whereas the interlocus homology increases, as the rate of gene conversion increases. The intralocus homology decreases, whereas the interlocus homology increases, as the proportion of symmetric heteroduplexes increases. The characteristic convergence time can be sufficiently short to imply that intrachromosomal gene conversion may be an important mechanism for maintaining sequence homogeneity among repeated genes. The convergence time decreases as the conversion rate and the proportion of symmetric heteroduplexes increase; although exceptions occur, it generally increases as the population size and the number of repeats increase; it may increase or decrease with increasing crossover rate.

Animals↗

PubMed2005

Evolution of host specificity in fleas: is it directional and irreversible?

Evolutionary trends in the evolution of host specificity have been the focus of much discussion but little rigorous empirical testing. On the one hand, specialization is often presumed to lead irreversibly into evolutionary dead ends and little diversification; this would mean that generalists might evolve into specialists, but not vice versa. On the other hand, low host specificity may limit the risk of extinction and provide more immediate fitness benefits to parasites, such that selection may favour evolution toward a generalist strategy. Here, we test for directionality in the evolution of host specificity using a large data set and phylogenetic information on 297 species of fleas parasitic on small mammals. The analyses determined whether host specificity, measured both as the number of host species exploited and their taxonomic diversity, was related to clade rank of the flea species, or the number of branching events between an extant species and the root of the phylogenetic tree (i.e., the total path length from the root of the tree to the species). Based on regression analyses, we found positive relationships between the number of host species used and clade rank across all 297 species, as well as within one (Hystrichopsyllidae) of four large families and one of seven large genera investigated separately; in addition, we found a positive relationship between the taxonomic diversity of host species used and clade rank in another of the seven genera. These results suggest a slight evolutionary trend of decreasing host specificity. Using a much more conservative likelihood ratio test, however, a random walk, or null model, of evolution could not be discarded in favour of the directional trends in all cases mentioned above. Still, these results suggest that host specificity may have tended to decrease in many flea lineages, a process that could have been driven by the benefits of exploiting a wide range of host species.

Adaptation, Biological↗

PubMed2000

Adaptation and the cost of complexity.

Adaptation is characterized by the movement of a population toward a many-character optimum, movement that results in an increase in fitness. Here I calculate the rate at which fitness increases during adaptation and describe the curve giving fitness versus time as a population approaches an optimum in Fisher's model of adaptation. The results identify several factors affecting the speed of adaptation. One of the most important is organismal complexity--complex organisms adapt more slowly than simple ones when using mutations of the same phenotypic size. Thus, as Fisher foresaw, organisms pay a kind of cost of complexity. However, the magnitude of this cost is considerably larger than Fisher's analysis suggested. Indeed the rate of adaptation declines at least as fast as n-1, where n is the number of independent characters or dimensions comprising an organism. The present results also suggest that one can define an effective number of dimensions characterizing an adapting species.

Adaptation, Physiological↗