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PubMed2002

Does multiple infection select for raised virulence?

Classical models of virulence evolution conclude that the increased competition favoured by multiple infection will select for increasing consumption and deterioration of the host resource, or 'virulence'. However, recent empirical and theoretical studies suggest that this view of virulence has some shortcomings. Here, we argue that the evolutionary consequences of multiple infection depend critically on whether the exploitation rate of an individual parasite is governed directly by the behaviour of the individual, or whether it is limited by the collective behaviour of the coinfecting group. We illustrate that, depending on the mechanistic details of exploitation, multiple infection can select for reduced virulence.

Biological Evolution↗

PubMed2003

Sexual selection favors female-biased sex ratios: the balance between the opposing forces of sex-ratio selection and sexual selection.

In a verbal model, Trivers and Willard proposed that, whenever there is sexual selection among males, natural selection should favor mothers that produce sons when in good condition but daughters when in poor condition. The predictions of this model have been the subject of recent debate. We present an explicit population genetic model for the evolution of a maternal-effect gene that biases offspring sex ratio. We show that, like local mate competition, sexual selection favors female-biased sex ratios whenever maternal condition affects the reproductive competitive ability of sons. However, Fisherian sex-ratio selection, which favors a balanced sex ratio, is an opposing force. We show that the evolution of maternal sex-ratio biasing by these opposing selection forces requires a positive covariance across environments between the sex-ratio bias toward sons (b) and the mating success of sons (r). This covariance alone is not a sufficient condition for the evolution of maternal sex-ratio biasing; it must be sufficiently positive to outweigh the opposing sex-ratio selection. To identify the necessary and sufficient conditions, we partition total evolutionary change into three components: (1) maternal sex-ratio bias, (2) sexual selection on sons, and (3) sex-ratio selection. Because the magnitude of the first component asymmetrically affects the strength of the second, biasing broods toward females in a poor environment evolves faster than the same degree of bias toward males in a good environment. Consequently, female-biased sex ratios, rather than male-biased sex ratios, are more likely to evolve. We discuss our findings in the context of the primary sex-ratio biases observed in strongly sexually selected species and indicate how this perspective can assist the experimental study of sex ratio evolution.

Alleles↗

PubMed2004

Bacterial proteins predisposed for targeting to mitochondria.

Mitochondria evolved from an endosymbiotic proteobacterium in a process that required the transfer of genes from the bacterium to the host cell nucleus, and the translocation of proteins thereby made in the host cell cytosol into the internal compartments of the organelle. According to current models for this evolution, two highly improbable events are required to occur simultaneously: creation of a protein translocation machinery to import proteins back into the endosymbiont and creation of targeting sequences on the protein substrates themselves. Using a combination of two independent prediction methods, validated through tests on simulated genomes, we show that at least 5% of proteins encoded by an extant proteobacterium are predisposed for targeting to mitochondria, and propose we that mitochondrial targeting information was preexisting for many proteins of the endosymbiont. We analyzed a family of proteins whose members exist both in bacteria and in mitochondria of eukaryotes and show that the amino-terminal extensions occasionally found in bacterial family members can function as a crude import sequence when the protein is presented to isolated mitochondria. This activity leaves the development of a primitive translocation channel in the outer membrane of the endosymbiont as a single hurdle to initiating the evolution of mitochondria.

Amino Acid Sequence↗

PubMed2003

Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors.

Pineal evolution is envisaged as a gradual transformation of pinealocytes (a gradual regression of pinealocyte sensory capacity within a particular cell line), the so-called sensory cell line of the pineal organ. In most non-mammals the pineal organ is a directly photosensory organ, while the pineal organ of mammals (epiphysis cerebri) is a non-sensory neuroendocrine organ under photoperiod control. The phylogenetic transformation of the pineal organ is reflected in the morphology and physiology of the main parenchymal cell type, the pinealocyte. In anamniotes, pinealocytes with retinal cone photoreceptor-like characteristics predominate, whereas in sauropsids so-called rudimentary photoreceptors predominate. These have well-developed secretory characteristics, and have been interpreted as intermediaries between the anamniote pineal photoreceptors and the mammalian non-sensory pinealocytes. We have re-examined the original studies on which the gradual transformation hypothesis of pineal evolution is based, and found that the evidence for this model of pineal evolution is ambiguous. In the light of recent advances in the understanding of neural development mechanisms, we propose a new hypothesis of pineal evolution, in which the old notion 'gradual regression within the sensory cell line' should be replaced with 'changes in fate restriction within the neural lineage of the pineal field'.

Animals↗

PubMed2003

Hydrodynamics of bacterial colonies: a model.

We propose a hydrodynamic model for the evolution of bacterial colonies growing on soft agar plates. This model consists of reaction-diffusion equations for the concentrations of nutrients, water, and bacteria, coupled to a single hydrodynamic equation for the velocity field of the bacteria-water mixture. It captures the dynamics inside the colony as well as on its boundary and allows us to identify a mechanism for collective motion towards fresh nutrients, which, in its modeling aspects, is similar to classical chemotaxis. As shown in numerical simulations, our model reproduces both usual colony shapes and typical hydrodynamic motions, such as the whirls and jets recently observed in wet colonies of Bacillus subtilis. The approach presented here could be extended to different experimental situations and provides a general framework for the use of advection-reaction-diffusion equations in modeling bacterial colonies.

Agar↗

PubMed2005

Glassy dynamics in the adaptive immune response prevents autoimmune disease.

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.

Animals↗

PubMed2002

Invasion of unisexuals in hermaphrodite populations of animal-pollinated plants: effects of pollination ecology and floral size-number trade-offs.

The most common sexual system in animal-pollinated plants is hermaphroditism, while some species are dioecious or gynodioecious and a very few are androdioecious. In this paper, I attempt to explain this pattern by extending previous models for the evolution of sexual systems to incorporate two main features: (1) a portion of investment in pollinator attraction contributes to only female or male function, because one sexual function of a flower is saturated with pollinator visitation earlier than the other sexual function; and (2) there are trade-offs between the size and number of flowers. The analysis was conducted to determine the conditions when females and males can increase in frequency in a hermaphroditic population, assuming either concave or convex pollinator gain curves (relation between investment to attractive structures of a flower and frequency of pollinator visits to the flower). The results suggest that both of the main factors play important roles in the evolution of plant sexual systems: uneven contribution of pollinator-attractive structures and nonlinear trade-offs between flower size and number can destabilize hermaphroditism. When a convex pollinator gain curve was assumed, the effect of nonlinear trade-offs can produce accelerating compensation from the elimination of one sexual function, allowing males to increase for large regions of parameter space, where females could not increase. The last prediction obviously conflicts with the observed rarity of androdioecy in nature, indicating the necessity of exploring pollinator gain curves in more detail.

Animals↗

PubMed2002

Evolution of drug resistance in Candida albicans.

The widespread deployment of antimicrobial agents in medicine and agriculture is nearly always followed by the evolution of resistance to these agents in the pathogen. With the limited availability of antifungal drugs and the increasing incidence of opportunistic fungal infections, the emergence of drug resistance in fungal pathogens poses a serious public health concern. Antifungal drug resistance has been studied most extensively with the yeast Candida albicans owing to its importance as an opportunistic pathogen and its experimental tractability relative to other medically important fungal pathogens. The emergence of antifungal drug resistance is an evolutionary process that proceeds on temporal, spatial, and genomic scales. This process can be observed through epidemiological studies of patients and through population-genetic studies of pathogen populations. Population-genetic studies rely on sampling of the pathogen in patient populations, serial isolations of the pathogen from individual patients, or experimental evolution of the pathogen in nutrient media or in animal models. Predicting the evolution of drug resistance is fundamental to prolonging the efficacy of existing drugs and to strategically developing and deploying novel drugs.

Antifungal Agents↗

PubMedDate not supplied

Managed care, market stages, and integrated delivery systems: is there a relationship?

This DataWatch evaluates four-stage models of market evolution developed initially by the University HealthSystem Consortium (UHC). Such models suggest that increasing health maintenance organization (HMO) penetration is linked with increases in hospital consolidation and vertical integration between physicians and hospitals. These claims are tested using national data for 1992-1995. Results suggest that such models accurately classify the markets of UHC member hospitals according to their levels of HMO penetration only. Moreover, they do not discern evolutionary stages of market development and may not be generalizable to the markets of non-UHC member hospitals. Researchers and policymakers should exercise caution in applying such models.

Delivery of Health Care, Integrated↗

PubMed2000

Spatial-temporal correlations in the process to self-organized criticality.

A different type of spatial-temporal correlation in the process approaching the self-organized criticality is investigated for the two simple models for biological evolution. The changed behaviors of the position with minimum barrier are shown to be quantitatively different in the two models. Different results of the correlation are given for the two models. We argue that the correlation can be used, together with the power-law distributions, as criteria for self-organized criticality.

Biological Evolution↗

PubMed1983

Intracellular compartmentation of isozymes of sugar phosphate metabolism in green leaves.

The present paper has summarized evidence for the presence of two isozymes for many enzyme activities of sugar phosphate metabolism in plant leaves. These two isozymes are clearly compartmentalized in the chloroplasts and in the cytosol of plant leaf cells. In C4 plants there exists an additional isozyme in the mesophyll cells of these leaves in addition to the two isozymes in the bundle sheath cells. Such cell-compartment-specific and cell-specific isozymes provide duplicate (and possibly triplicate) enzyme systems for complete or almost complete pathways (ie, glycolysis, gluconeogenesis, and the oxidative pentose phosphate pathway). They provide a basis for the understanding as to how many isozymes one may expect in plants. They also provide a challenge to determine what their function is particularly in the differential regulation of metabolic pathways in different cell compartments. Based on his genetic analyses Weeden [1981] has recently proposed a model for the evolution of chloroplast-specific isozymes of sugar phosphate metabolism. This model rests on the endosymbiotic theory for the origin of chloroplasts. It still is highly speculative. However, cell-compartment specific isozymes may eventually provide a means of studying plant evolution, especially if we succeed in analyzing their primary structure.

Antigen-Antibody Complex↗

PubMed2003

The EBG system of E. coli: origin and evolution of a novel beta-galactosidase for the metabolism of lactose.

The EBG system of E. coli has served as a model for the evolution of novel functions. This paper reviews the experimental evolution of the catabolism of beta-galactoside sugars in strains of E. coli that carry deletions of the classical lacZ beta-galactosidase gene. Evolution of the ebgA encoded Ebg beta-galactosidase for an expanded substrate range, evolution of the ebgR encoded Ebg repressor for sensitivity to an expanded range of inducers, the amino acid replacements responsible for those changes, and the evolutionary potential of the system are discussed. The EBG system has also served as a model for studying the detailed catalytic consequences of experimental evolution at the physical-chemical level. The analysis of free-energy profiles for the wildtype and all of the various evolved Ebg enzymes has permitted rejection of the Albery-Knowles hypothesis that relates likely changes in free-energy profiles to evolutionary change.

Crosses, Genetic↗

PubMed2005

Duplication-divergence model of protein interaction network.

We investigate a very simple model describing the evolution of protein-protein interaction networks via duplication and divergence. The model exhibits a remarkably rich behavior depending on a single parameter, the probability to retain a duplicated link during divergence. When this parameter is large, the network growth is not self-averaging and an average node degree increases algebraically. The lack of self-averaging results in a great diversity of networks grown out of the same initial condition. When less than a half of links are (on average) preserved after divergence, the growth is self-averaging, the average degree increases very slowly or tends to a constant, and a degree distribution has a power-law tail. The predicted degree distributions are in a very good agreement with the distributions observed in real protein networks.

Computer Simulation↗

PubMed2001

Stochastic population models with interacting species.

A stochastic model concerning the evolution of a multi-species population is presented assuming species competition for a habitat. The model takes into account colonization, death and replacement for all individuals. Two cases are treated: (i) colonizations follow the hierarchic rule by which species of lower rank are always outcompeted by those of higher rank and (ii) there are no privileged species. In both cases, under suitable assumptions, a thorough description of the evolution of the population is obtained. The two models are finally compared and the corresponding evolutionary behaviors of the populations are discussed.

Animals↗

PubMed2007

Clonal and parallel evolution of primary lung cancers and their metastases revealed by molecular dissection of cancer cells.

PURPOSE: Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been proposed to date. The purpose of this study is to investigate the authenticity of these models by comparison of accumulated genetic alterations between primary and corresponding metastatic lung cancers. EXPERIMENTAL DESIGN: A whole-genome allelic imbalance scanning using a high-resolution single nucleotide polymorphism array and mutational analysis of the p53, EGFR, and KRAS genes were done on eight sets of primary and metastatic lung cancers. Based on the genotype data, the natural history of each case was deduced, and candidate metastasis suppressor loci were determined. RESULTS: Five to 20 chromosomal regions showed allelic imbalance in each tumor. Accumulated genetic alterations were similar between primary and corresponding metastatic tumors, and the majority(>67%) of genetic alterations detected in metastatic tumors was also detected in the corresponding primary tumors. On the other hand, in seven of the eight cases, there were genetic alterations accumulated only in metastatic tumors. Among these alterations, allelic imbalances at chromosome 11p15 and 11p11-p13 regions were the most frequent ones (4 of 8, 50%). Likewise, four cases showed genetic alterations detected only in primary tumors. CONCLUSIONS: The natural history of each case indicated that the process of metastasis varies among cases, and that all three models are applicable to lung cancer progression. According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is present on chromosome 11p.

Adult↗

PubMed2004

A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process.

Most current models of sequence evolution assume that all sites of a protein evolve under the same substitution process, characterized by a 20 x 20 substitution matrix. Here, we propose to relax this assumption by developing a Bayesian mixture model that allows the amino-acid replacement pattern at different sites of a protein alignment to be described by distinct substitution processes. Our model, named CAT, assumes the existence of distinct processes (or classes) differing by their equilibrium frequencies over the 20 residues. Through the use of a Dirichlet process prior, the total number of classes and their respective amino-acid profiles, as well as the affiliations of each site to a given class, are all free variables of the model. In this way, the CAT model is able to adapt to the complexity actually present in the data, and it yields an estimate of the substitutional heterogeneity through the posterior mean number of classes. We show that a significant level of heterogeneity is present in the substitution patterns of proteins, and that the standard one-matrix model fails to account for this heterogeneity. By evaluating the Bayes factor, we demonstrate that the standard model is outperformed by CAT on all of the data sets which we analyzed. Altogether, these results suggest that the complexity of the pattern of substitution of real sequences is better captured by the CAT model, offering the possibility of studying its impact on phylogenetic reconstruction and its connections with structure-function determinants.

Amino Acid Sequence↗

PubMed1997

Comparable rates of gene loss and functional divergence after genome duplications early in vertebrate evolution.

Duplicated genes are an important source of new protein functions and novel developmental and physiological pathways. Whereas most models for fate of duplicated genes show that they tend to be rapidly lost, models for pathway evolution suggest that many duplicated genes rapidly acquire novel functions. Little empirical evidence is available, however, for the relative rates of gene loss vs. divergence to help resolve these contradictory expectations. Gene families resulting from genome duplications provide an opportunity to address this apparent contradiction. With genome duplication, the number of duplicated genes in a gene family is at most 2n, where n is the number of duplications. The size of each gene family, e.g., 1, 2, 3, ..., 2n, reflects the patterns of gene loss vs. functional divergence after duplication. We focused on gene families in humans and mice that arose from genome duplications in early vertebrate evolution and we analyzed the frequency distribution of gene family size, i.e., the number of families with two, three or four members. All the models that we evaluated showed that duplicated genes are almost as likely to acquire a new and essential function as to be lost through acquisition of mutations that compromise protein function. An explanation for the unexpectedly high rate of functional divergence is that duplication allows genes to accumulate more neutral than disadvantageous mutations, thereby providing more opportunities to acquire diversified functions and pathways.

Animals↗

PubMed2004

A maximum principle for the mutation-selection equilibrium of nucleotide sequences.

We study the equilibrium behaviour of a deterministic four-state mutation-selection model as a model for the evolution of a population of nucleotide sequences in sequence space. The mutation model is the Kimura 3ST mutation scheme, and the selection scheme is assumed to be invariant under permutation of sites. Considering the evolution process both forward and backward in time, we use the ancestral distribution as the stationary state of the backward process to derive an expression for the mutational loss (as the difference between ancestral and population mean fitness), and we prove a maximum principle that determines the population mean fitness in mutation-selection balance.

Animals↗