1,893 research outputs found

    Gene Hutson, Plaintiff, v. Covidien, Inc., Defendant.

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    Properties of selected mutations and genotypic landscapes under Fisher's Geometric Model

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    The fitness landscape - the mapping between genotypes and fitness - determines properties of the process of adaptation. Several small genetic fitness landscapes have recently been built by selecting a handful of beneficial mutations and measuring fitness of all combinations of these mutations. Here we generate several testable predictions for the properties of these landscapes under Fisher's geometric model of adaptation (FGMA). When far from the fitness optimum, we analytically compute the fitness effect of beneficial mutations and their epistatic interactions. We show that epistasis may be negative or positive on average depending on the distance of the ancestral genotype to the optimum and whether mutations were independently selected or co-selected in an adaptive walk. Using simulations, we show that genetic landscapes built from FGMA are very close to an additive landscape when the ancestral strain is far from the optimum. However, when close to the optimum, a large diversity of landscape with substantial ruggedness and sign epistasis emerged. Strikingly, landscapes built from different realizations of stochastic adaptive walks in the same exact conditions were highly variable, suggesting that several realizations of small genetic landscapes are needed to gain information about the underlying architecture of the global adaptive landscape.Comment: 51 pages, 8 figure

    On the Duality of Semiantichains and Unichain Coverings

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    We study a min-max relation conjectured by Saks and West: For any two posets PP and QQ the size of a maximum semiantichain and the size of a minimum unichain covering in the product P×QP\times Q are equal. For positive we state conditions on PP and QQ that imply the min-max relation. Based on these conditions we identify some new families of posets where the conjecture holds and get easy proofs for several instances where the conjecture had been verified before. However, we also have examples showing that in general the min-max relation is false, i.e., we disprove the Saks-West conjecture.Comment: 10 pages, 3 figure

    Selective sweeps under dominance and inbreeding

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    A major research goal in evolutionary genetics is to uncover loci experiencing positive selection. One approach involves finding ‘selective sweeps’ patterns, which can either be ‘hard sweeps’ formed by de novo mutation, or ‘soft sweeps’ arising from recurrent mutation or existing standing variation. Existing theory generally assumes outcrossing populations, and it is unclear how dominance affects soft sweeps. We consider how arbitrary dominance and inbreeding via self-fertilization affect hard and soft sweep signatures. With increased self-fertilization, they are maintained over longer map distances due to reduced effective recombination and faster beneficial allele fixation times. Dominance can affect sweep patterns in outcrossers if the derived variant originates from either a single novel allele, or from recurrent mutation. These models highlight the challenges in distinguishing hard and soft sweeps, and propose methods to differentiate between scenarios

    Variation of the adaptive substitution rate between species and within genomes

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    The importance of adaptive mutations in molecular evolution is extensively debated. Recent developments in population genomics allow inferring rates of adaptive mutations by fitting a distribution of fitness effects to the observed patterns of polymorphism and divergence at sites under selection and sites assumed to evolve neutrally. Here, we summarize the current state-of-the-art of these methods and review the factors that affect the molecular rate of adaptation. Several studies have reported extensive cross-species variation in the proportion of adaptive amino-acid substitutions (α) and predicted that species with larger effective population sizes undergo less genetic drift and higher rates of adaptation. Disentangling the rates of positive and negative selection, however, revealed that mutations with deleterious effects are the main driver of this population size effect and that adaptive substitution rates vary comparatively little across species. Conversely, rates of adaptive substitution have been documented to vary substantially within genomes. On a genome-wide scale, gene density, recombination and mutation rate were observed to play a role in shaping molecular rates of adaptation, as predicted under models of linked selection. At the gene level, it has been reported that the gene functional category and the macromolecular structure substantially impact the rate of adaptive mutations. Here, we deliver a comprehensive review of methods used to infer the molecular adaptive rate, the potential drivers of adaptive evolution and how positive selection shapes molecular evolution within genes, across genes within species and between species

    RATES OF FITNESS DECLINE AND REBOUND SUGGEST PERVASIVE EPISTASIS

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    Unraveling the factors that determine the rate of adaptation is a major question in evolutionary biology. One key parameter is the effect of a new mutation on fitness, which invariably depends on the environment and genetic background. The fate of a mutation also depends on population size, which determines the amount of drift it will experience. Here, we manipulate both population size and genotype composition and follow adaptation of 23 distinct Escherichia coli genotypes. These have previously accumulated mutations under intense genetic drift and encompass a substantial fitness variation. A simple rule is uncovered: the net fitness change is negatively correlated with the fitness of the genotype in which new mutations appear--a signature of epistasis. We find that Fisher's geometrical model can account for the observed patterns of fitness change and infer the parameters of this model that best fit the data, using Approximate Bayesian Computation. We estimate a genomic mutation rate of 0.01 per generation for fitness altering mutations, albeit with a large confidence interval, a mean fitness effect of mutations of -0.01, and an effective number of traits nine in mutS(-) E. coli. This framework can be extended to confront a broader range of models with data and test different classes of fitness landscape models.LAO/ITQB, FCT, Danish Council for Independent Research

    Travail de l’anthropologue et travail des témoins, Moskitia 1982-2007

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    Comment les acteurs de conflits armés et les observateurs de ces conflits perçoivent-ils les événements auxquels ils participent ou dont ils s’efforcent de rendre compte ? Quels sont les biais de leurs perceptions ? Le recueil puis l’analyse d’une centaine de récits de vie de guérilleros miskitus du Nicaraga met en évidence la part de l’aléatoire et de l’accidentel et le poids du contexte socio-politique sur les processus qui mènent des individus à s’engager dans une guerre civile. Ces récits de vie illustrent aussi combien le contexte pèse sur les perceptions et les narrations des acteurs sur le moment ou a posteriori. Les récits de vie des anciens guérilleros miskitus sont aussi marqués par toute une tradition protestante morave mettant à l’honneur l’idée d’une vérité plurielle. Gilles Bataillon s’interroge ici sur le sens et les modalités d’une réflexion sur une guerres civile, celle qui opposa les guérilleros miskitus aux sandinistes (Nicaragua 1982-1987), et sur les modalités de la mise en forme du passé.How do actors of armed conflicts and the observers of these conflicts perceive the events which they participate in or try to account for ? What are the actual biases of their perceptions ? The collect and analysis of a hundred life stories of Miskitu guerrillas from Nicaragua highlights the role of the unpredictable and the accidental, and of socio-political context on the processes that lead individuals to involve themselves in civil war. These life stories also illuminate the weight of context on the perceptions and narratives of actors, either on the spot or at a later moment. The life stories of former Miskitu guerrillas are also marked by a whole Moravian protestant tradition, which honours the idea of a plural truth. In this piece, Gilles Bataillon interrogates the meaning and modalities of a reflection on a civil war, which opposed the Miskitu guerrillas to the Sandinists in Nicaragua between 1982 and 1987, as well as the modalities through which the past can be put in shape

    Analyser le chaos

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    Comment analyser les situations-limites tels les expériences d’hyperinflation, les chevauchements de violences prosaïques et stratégiques, ou les déclins des identités sociales. Jusqu’à il y a peu de telles expériences étaient décrites et interprétées au regard de paradigmes sociologiques concevant les sociétés comme des totalités unifiées . On cherchait avant tout à mesurer dans différents secteurs de pratiques, des déficits par rapport à ce modèle intégrateur. De même essayait-on de les rap..
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