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A novel evolutionary drug scheduling model in cancer chemotherapy.

In this paper, we introduce a modified optimal control model of drug scheduling in cancer chemotherapy and a new adaptive elitist-population-based genetic algorithm (AEGA) to solve it. Working closely with an oncologist, we first modify the existing model, because its equation for the cumulative drug toxicity is inconsistent with medical knowledge and clinical experience. To explore multiple efficient drug scheduling policies, we propose a novel variable representation--a cycle-wise representation, and modify the elitist genetic search operators in the AEGA. The simulation results obtained by the modified model match well with the clinical treatment experiences, and can provide multiple efficient solutions for oncologists to consider. Moreover, it has been shown that the evolutionary drug scheduling approach is simple, and capable of solving complex cancer chemotherapy problems by adapting multimodal versions of evolutionary algorithms.

Algorithms↗

Generating high-speed dynamic running gaits in a quadruped robot using an evolutionary search.

Over the past several decades, there has been a considerable interest in investigating high-speed dynamic gaits for legged robots. While much research has been published, both in the biomechanics and engineering fields regarding the analysis of these gaits, no single study has adequately characterized the dynamics of high-speed running as can be achieved in a realistic, yet simple, robotic system. The goal of this paper is to find the most energy-efficient, natural, and unconstrained gallop that can be achieved using a simulated quadrupedal robot with articulated legs, asymmetric mass distribution, and compliant legs. For comparison purposes, we also implement the bound and canter. The model used here is planar, although we will show that it captures much of the predominant dynamic characteristics observed in animals. While it is not our goal to prove anything about biological locomotion, the dynamic similarities between the gaits we produce and those found in animals does indicate a similar underlying dynamic mechanism. Thus, we will show that achieving natural, efficient high-speed locomotion is possible even with a fairly simple robotic system. To generate the high-speed gaits, we use an efficient evolutionary algorithm called set-based stochastic optimization. This algorithm finds open-loop control parameters to generate periodic trajectories for the body. Several alternative methods are tested to generate periodic trajectories for the legs. The combined solutions found by the evolutionary search and the periodic-leg methods, over a range of speeds up to 10.0 m/s, reveal "biological" characteristics that are emergent properties of the underlying gaits.

Algorithms↗

Evolutionary design of a fuzzy classifier from data.

Genetic algorithms show powerful capabilities for automatically designing fuzzy systems from data, but many proposed methods must be subjected to some minimal structure assumptions, such as rule base size. In this paper, we also address the design of fuzzy systems from data. A new evolutionary approach is proposed for deriving a compact fuzzy classification system directly from data without any a priori knowledge or assumptions on the distribution of the data. At the beginning of the algorithm, the fuzzy classifier is empty with no rules in the rule base and no membership functions assigned to fuzzy variables. Then, rules and membership functions are automatically created and optimized in an evolutionary process. To accomplish this, parameters of the variable input spread inference training (VISIT) algorithm are used to code fuzzy systems on the training data set. Therefore, we can derive each individual fuzzy system via the VISIT algorithm, and then search the best one via genetic operations. To evaluate the fuzzy classifier, a fuzzy expert system acts as the fitness function. This fuzzy expert system can effectively evaluate the accuracy and compactness at the same time. In the application section, we consider four benchmark classification problems: the iris data, wine data, Wisconsin breast cancer data, and Pima Indian diabetes data. Comparisons of our method with others in the literature show the effectiveness of the proposed method.

Algorithms↗

A study of evolutionary multiagent models based on symbiosis.

Multiagent Systems with Symbiotic Learning and Evolution (Masbiole) has been proposed and studied, which is a new methodology of Multiagent Systems (MAS) based on symbiosis in the ecosystem. Masbiole employs a method of symbiotic learning and evolution where agents can learn or evolve according to their symbiotic relations toward others, i.e., considering the benefits/losses of both itself and an opponent. As a result, Masbiole can escape from Nash Equilibria and obtain better performances than conventional MAS where agents consider only their own benefits. This paper focuses on the evolutionary model of Masbiole, and its characteristics are examined especially with an emphasis on the behaviors of agents obtained by symbiotic evolution. In the simulations, two ideas suitable for the effective analysis of such behaviors are introduced; "Match Type Tile-world (MTT)" and "Genetic Network Programming (GNP)". MTT is a virtual model where tile-world is improved so that agents can behave considering their symbiotic relations. GNP is a newly developed evolutionary computation which has the directed graph type gene structure and enables to analyze the decision making mechanism of agents easily. Simulation results show that Masbiole can obtain various kinds of behaviors and better performances than conventional MAS in MTT by evolution.

Algorithms↗

Finding evolutionary relations beyond superfamilies: fold-based superfamilies.

Superfamily classifications are based variably on similarity of sequences, global folds, local structures, or functions. We have examined the possibility of defining superfamilies purely from the viewpoint of the global fold/function relationship. For this purpose, we first classified protein domains according to the beta-sheet topology. We then introduced the concept of kinship relations among the classified beta-sheet topology by assuming that the major elementary event leading to creation of a new beta-sheet topology is either an addition or deletion of one beta-strand at the edge of an existing beta-sheet during the molecular evolution. Based on this kinship relation, a network of protein domains was constructed so that the distance between a pair of domains represents the number of evolutionary events that lead one from the other domain. We then mapped on it all known domains with a specific core chemical function (here taken, as an example, that involving ATP or its analogs). Careful analyses revealed that the domains are found distributed on the network as >20 mutually disjointed clusters. The proteins in each cluster are defined to form a fold-based superfamily. The results indicate that >20 ATP-binding protein superfamilies have been invented independently in the process of molecular evolution, and the conservative evolutionary diffusion of global folds and functions is the origin of the relationship between them.

Adenosine Triphosphate↗

Simple evolutionary pathways to complex proteins.

A recent paper in this journal has challenged the idea that complex adaptive features of proteins can be explained by known molecular, genetic, and evolutionary mechanisms. It is shown here that the conclusions of this prior work are an artifact of unwarranted biological assumptions, inappropriate mathematical modeling, and faulty logic. Numerous simple pathways exist by which adaptive multi-residue functions can evolve on time scales of a million years (or much less) in populations of only moderate size. Thus, the classical evolutionary trajectory of descent with modification is adequate to explain the diversification of protein functions.

Evolution, Molecular↗

The evolutionary origins and catalytic importance of conserved electrostatic networks within TIM-barrel proteins.

Conservation of function is the basic tenet of protein evolution. Conservation of key electrostatic properties is a frequently employed mechanism that leads to conserved function. In a previous report, we identified several conserved electrostatic properties in four protein families and one functionally diverse enzyme superfamily. In this report, we demonstrate the evolutionary and catalytic importance of electrostatic networks in three ubiquitous metabolic enzymes: triosephosphate isomerase, enolase, and transaldolase. Evolutionary importance is demonstrated using phylogenetic motifs (sequence fragments that parallel the overall familial phylogeny). Phylogenetic motifs frequently correspond to both catalytic residues and conserved interactions that fine-tune catalytic residue pKa values. Further, in the case of triosephosphate isomerase, quantitative differences in the catalytic Glu169 pKa values parallel subfamily differentiation. Finally, phylogenetic motifs are shown to structurally cluster around the active sites of eight different TIM-barrel families. Depending upon the mechanistic requisites of each reaction catalyzed, interruptions to the canonical fold may or may not be identified as phylogenetic motifs.

Amino Acid Sequence↗

GEM: a Gaussian Evolutionary Method for predicting protein side-chain conformations.

We have developed an evolutionary approach to predicting protein side-chain conformations. This approach, referred to as the Gaussian Evolutionary Method (GEM), combines both discrete and continuous global search mechanisms. The former helps speed up convergence by reducing the size of rotamer space, whereas the latter, integrating decreasing-based Gaussian mutations and self-adaptive Gaussian mutations, continuously adapts dihedrals to optimal conformations. We tested our approach on 38 proteins ranging in size from 46 to 325 residues and showed that the results were comparable to those using other methods. The average accuracies of our predictions were 80% for chi(1), 66% for chi(1 + 2), and 1.36 A for the root mean square deviation of side-chain positions. We found that if our scoring function was perfect, the prediction accuracy was also essentially perfect. However, perfect prediction could not be achieved if only a discrete search mechanism was applied. These results suggest that GEM is robust and can be used to examine the factors limiting the accuracy of protein side-chain prediction methods. Furthermore, it can be used to systematically evaluate and thus improve scoring functions.

Algorithms↗

The Baldwin effect: a neglected influence on C. G. Jung's evolutionary thinking.

This paper considers the claim that C. G. Jung used a Lamarckian model of evolution to underwrite his theory of archetypes. This claim is challenged on the basis of Jung's familiarity with and use of the writings of James Mark Baldwin and Conway Lloyd Morgan, both of whom were noted and forceful opponents of neo-Lamarckian theory from within a neo-Darwinian framework. The paper then outlines the evolutionary model proposed by Baldwin and Lloyd Morgan, which has come to be known as Baldwinian evolution or the Baldwin effect. This model explicitly views psychological factors as central to the evolutionary process. Finally, the use of Baldwinian thinking in contemporary theorizing regarding language and other symbolic systems is reviewed and suggestions are made regarding the implications of Baldwinian models for theory building in analytical psychology.

Animals↗

Evolutionary dynamics of pathogen resistance and tolerance.

Host organisms can respond to the threat of disease either through resistance defenses (which inhibit or limit infection) or through tolerance strategies (which do not limit infection, but reduce or offset its fitness consequences). Here we show that resistance and tolerance can have fundamentally different evolutionary outcomes, even when they have equivalent short-term benefit for the host. As a gene conferring disease resistance spreads through a population, the incidence of infection declines, reducing the fitness advantage of carrying the resistance gene. Thus genes conferring complete resistance cannot become fixed (i.e., universal) by selection in a host population, and diseases cannot be eliminated solely by natural selection for host resistance. By contrast, as a gene conferring disease tolerance spreads through a population, disease incidence rises, increasing the evolutionary advantage of carrying the tolerance gene. Therefore, any tolerance gene that can invade a host population will tend to be driven to fixation by selection. As predicted, field studies of diverse plant species infected by rust fungi confirm that resistance traits tend to be polymorphic and tolerance traits tend to be fixed. These observations suggest a new mechanism for the evolution of mutualism from parasitism, and they help to explain the ubiquity of disease.

Animals↗

Imitating the initial evolutionary stage of a tail ornament.

Costs of a sexual ornament in its early evolutionary form and the relationship between these costs and individual condition may be an important influence in the likelihood of possible evolutionary mechanisms involved in the evolution of this ornament. We reconstructed the tail shape in hypothetical ancestors of recent hirundines (Aves: Hirundinidae), from which the elongation of tail feathers under sexual selection might have begun. By elongating the tail in sand martins (Riparia riparia, Hirundinidae), we simulated the early evolution of a long forked tail--the typical ornament of male hirundines. Birds with initial ornament captured smaller insects than controls, which suggests that this ornament imposed a cost in terms of impaired foraging. Furthermore, birds with naturally longer tails were better able to cope with initial ornament than naturally short-tailed birds. If length of tail in sand martins indicates the quality of individuals, our results suggest higher costs of this initial ornament for poorer than for higher quality individuals. We discuss the potential role of the handicap principle and other mechanisms in early evolution of a tail ornament.

Animals↗

Evolutionary optimality applied to Drosophila experiments: hypothesis of constrained reproductive efficiency.

The general purpose of the paper is to test evolutionary optimality theories with experimental data on reproduction, energy consumption, and longevity in a particular Drosophila genotype. We describe the resource allocation in Drosophila females in terms of the oxygen consumption rates devoted to reproduction and to maintenance. The maximum ratio of the component spent on reproduction to the total rate of oxygen consumption, which can be realized by the female reproductive machinery, is called metabolic reproductive efficiency (MRE). We regard MRE as an evolutionary constraint. We demonstrate that MRE may be evaluated for a particular Drosophila phenotype given the fecundity pattern, the age-related pattern of oxygen consumption rate, and the longevity. We use a homeostatic model of aging to simulate a life history of a representative female fly, which describes the control strain in the long-term experiments with the Wayne State Drosophila genotype. We evaluate the theoretically optimal trade-offs in this genotype. Then we apply the Van Noordwijk-de Jong resource acquisition and allocation model, Kirkwood's disposable soma theory. and the Partridge-Barton optimality approach to test if the experimentally observed trade-offs may be regarded as close to the theoretically optimal ones. We demonstrate that the two approaches by Partridge-Barton and Kirkwood allow a positive answer to the question, whereas the Van Noordwijk-de Jong approach may be used to illustrate the optimality. We discuss the prospects of applying the proposed technique to various Drosophila experiments, in particular those including manipulations affecting fecundity.

Aging↗

Perspective: Genetic assimilation and a possible evolutionary paradox: can macroevolution sometimes be so fast as to pass us by?

The idea of genetic assimilation, that environmentally induced phenotypes may become genetically fixed and no longer require the original environmental stimulus, has had varied success through time in evolutionary biology research. Proposed by Waddington in the 1940s, it became an area of active empirical research mostly thanks to the efforts of its inventor and his collaborators. It was then attacked as of minor importance during the "hardening" of the neo-Darwinian synthesis and was relegated to a secondary role for decades. Recently, several papers have appeared, mostly independently of each other, to explore the likelihood of genetic assimilation as a biological phenomenon and its potential importance to our understanding of evolution. In this article we briefly trace the history of the concept and then discuss theoretical models that have newly employed genetic assimilation in a variety of contexts. We propose a typical scenario of evolution of genetic assimilation via an intermediate stage of phenotypic plasticity and present potential examples of the same. We also discuss a conceptual map of current and future lines of research aimed at exploring the actual relevance of genetic assimilation for evolutionary biology.

Adaptation, Biological↗

Evolutionary history of the northern leopard frog: reconstruction of phylogeny, phylogeography, and historical changes in population demography from mitochondrial DNA.

This study uses a combined methodological approach including phylogenetic, phylogeographic, and demographic analyses to understand the evolutionary history of the northern leopard frog, Rana pipiens. We tested hypotheses concerning how (or if) known geological events and key features of the species biology influenced the contemporary geographic and genetic distribution of R. pipiens. We assayed mitochondrial DNA variation from 389 individuals within 35 populations located throughout the species range. Our a priori expectations for patterns and processes influencing the current genetic structure of R. pipiens were supported by the data. However, our analyses revealed specific aspects of R. pipiens evolutionary history that were unexpected. The phylogenetic analysis indicated that R. pipiens is split into populations containing discrete eastern or western haplotypes, with the Mississippi River and Great Lakes region dividing the geographic ranges. Nested clade analysis indicated that the biological process most often invoked to explain the pattern of haplotype position is restricted gene flow with isolation by distance. Demographic analyses showed evidence of both historical bottlenecks and population expansions. Surprisingly, the genetic evidence indicated that the western haplotypes had significantly reduced levels of genetic diversity relative to the eastern haplotypes and that major range expansions occurred in both regions well before the most recent glacial retreat. This study provides a detailed history of how a widespread terrestrial vertebrate responded to episodic Pleistocene glacial events in North America. Moreover, this study illustrates how complementary methods of data analysis can be used to disentangle recent and ancient effects on the genetic structure of a species.

Animals↗

Evolution of the vertebrate jaw: comparative embryology and molecular developmental biology reveal the factors behind evolutionary novelty.

It is generally believed that the jaw arose through the simple transformation of an ancestral rostral gill arch. The gnathostome jaw differentiates from Hox-free crest cells in the mandibular arch, and this is also apparent in the lamprey. The basic Hox code, including the Hox-free default state in the mandibular arch, may have been present in the common ancestor, and jaw patterning appears to have been secondarily constructed in the gnathostomes. The distribution of the cephalic neural crest cells is similar in the early pharyngula of gnathostomes and lampreys, but different cell subsets form the oral apparatus in each group through epithelial-mesenchymal interactions: and this heterotopy is likely to have been an important evolutionary change that permitted jaw differentiation. This theory implies that the premandibular crest cells differentiate into the upper lip, or the dorsal subdivision of the oral apparatus in the lamprey, whereas the equivalent cell population forms the trabecula of the skull base in gnathostomes. Because the gnathostome oral apparatus is derived exclusively from the mandibular arch, the concepts 'oral' and 'mandibular' must be dissociated. The 'lamprey trabecula' develops from mandibular mesoderm, and is not homologous with the gnathostome trabecula, which develops from premandibular crest cells. Thus the jaw evolved as an evolutionary novelty through tissue rearrangements and topographical changes in tissue interactions.

Animals↗

Quantitative trait locus analyses and the study of evolutionary process.

The past decade has seen a proliferation of studies that employ quantitative trait locus (QTL) approaches to diagnose the genetic basis of trait evolution. Advances in molecular techniques and analytical methods have suggested that an exact genetic description of the number and distribution of genes affecting a trait can be obtained. Although this possibility has met with some success in model systems such as Drosophila and Arabidopsis, the pursuit of an exact description of QTL effects, i.e. individual gene effect, in most cases has proven problematic. We discuss why QTL methods will have difficulty in identifying individual genes contributing to trait variation, and distinguish between the identification of QTL (or marker intervals) and the identification of individual genes or nucleotide differences within genes (QTN). This review focuses on what ecologists and evolutionary biologists working with natural populations can realistically expect to learn from QTL studies. We highlight representative issues in ecology and evolutionary biology and discuss the range of questions that can be addressed satisfactorily using QTL approaches. We specifically address developing approaches to QTL analysis in outbred populations, and discuss practical considerations of experimental (cross) design and application of different marker types. Throughout this review we attempt to provide a balanced description of the benefits of QTL methodology to studies in ecology and evolution as well as the inherent assumptions and limitations that may constrain its application.

Adaptation, Biological↗

Evolutionary history of the European whitefish Coregonus lavaretus (L.) species complex as inferred from mtDNA phylogeography and gill-raker numbers.

We compared mitochondrial DNA and gill-raker number variation in populations of the European whitefish Coregonus lavaretus (L.) species complex to illuminate their evolutionary history, and discuss mechanisms behind diversification. Using single-strand conformation polymorphism (SSCP) and sequencing 528 bp of combined parts of the cytochrome oxidase b (cyt b) and NADH dehydrogenase subunit 3 (ND3) mithochondrial DNA (mtDNA) regions, we documented phylogeographic relationships among populations and phylogeny of mtDNA haplotypes. Demographic events behind geographical distribution of haplotypes were inferred using nested clade analysis (NCA) and mismatch distribution. Concordance between operational taxonomical groups, based on gill-raker numbers, and mtDNA patterns was tested. Three major mtDNA clades were resolved in Europe: a North European clade from northwest Russia to Denmark, a Siberian clade from the Arctic Sea to southwest Norway, and a South European clade from Denmark to the European Alps, reflecting occupation in different glacial refugia. Demographic events inferred from NCA were isolation by distance, range expansion, and fragmentation. Mismatch analysis suggested that clades which colonized Fennoscandia and the Alps expanded in population size 24 500-5800 years before present, with minute female effective population sizes, implying small founder populations during colonization. Gill-raker counts did not commensurate with hierarchical mtDNA clades, and poorly with haplotypes, suggesting recent origin of gill-raker variation. Whitefish designations based on gill-raker numbers were not associated with ancient clades. Lack of congruence in morphology and evolutionary lineages implies that the taxonomy of this species complex should be reconsidered.

Animals↗

Bayesian inference of evolutionary history from chloroplast microsatellites in the cosmopolitan weed Capsella bursa-pastoris (Brassicaceae).

Besides showing an extraordinary degree of phenotypic variability, Capsella bursa-pastoris (Brassicaceae) is also one of the world's most common plant species and a serious weed in many countries. We have employed a coalescent-based Bayesian analysis of chloroplast microsatellite data to infer demographic and evolutionary parameters of this species. Two different demographic models applied to data from seven chloroplast microsatellite loci among 59 accessions show that the effective population size of C. bursa-pastoris is very small indicating a rapid expansion of the species, a result that is in accordance with fossil and historical data. Against this background, analysis of flowering time variation among accessions suggests that ecotypic differentiation in flowering time has occurred recently in the species' history. Finally, our results also indicate that mononucleotide repeat loci in the chloroplast genome can deteriorate in relatively short periods of evolutionary time.

Base Sequence↗