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COMPLEX TIME: Adaptation, Aging, & Arrow of Time

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Models relating phenotype space to fitness (phenotype-fitness landscapes) have seen important developments recently. They can roughly be divided into mechanistic models (e.g., metabolic networks) and more heuristic models like Fisher's geometrical model. Each has its own drawbacks, but both yield testable predictions on how the context (genomic background or environment) affects the distribution of mutation effects on fitness and thus adaptation. Both have received some empirical validation. This article aims at bridging the gap between these approaches. A derivation of the Fisher model "from first principles" is proposed, where the basic assumptions emerge from a more general model, inspired by mechanistic networks. I start from a general phenotypic network relating unspecified phenotypic traits and fitness. A limited set of qualitative assumptions is then imposed, mostly corresponding to known features of phenotypic networks: a large set of traits is pleiotropically affected by mutations and determines a much smaller set of traits under optimizing selection. Otherwise, the model remains fairly general regarding the phenotypic processes involved or the distribution of mutation effects affecting the network. A statistical treatment and a local approximation close to a fitness optimum yield a landscape that is effectively the isotropic Fisher model or its extension with a single dominant phenotypic direction. The fit of the resulting alternative distributions is illustrated in an empirical data set. These results bear implications on the validity of Fisher's model's assumptions and on which features of mutation fitness effects may vary (or not) across genomic or environmental contexts.  +
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Much research debates whether properties of ecological networks such as nestedness and con- nectance stabilise biological communities while ignoring key behavioural aspects of organisms within these networks. Here, we computationally assess how adaptive foraging (AF) behaviour interacts with network architecture to determine the stability of plant–pollinator networks. We find that AF reverses negative effects of nestedness and positive effects of connectance on the sta- bility of the networks by partitioning the niches among species within guilds. This behaviour enables generalist pollinators to preferentially forage on the most specialised of their plant part- ners which increases the pollination services to specialist plants and cedes the resources of general- ist plants to specialist pollinators. We corroborate these behavioural preferences with intensive field observations of bee foraging. Our results show that incorporating key organismal behaviours with well-known biological mechanisms such as consumer-resource interactions into the analysis of ecological networks may greatly improve our understanding of complex ecosystems.  +
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Phenotypic variation is common in most pathogens, yet the mechanisms that maintain this diver- sity are still poorly understood. We asked whether continuous host variation in susceptibility helps maintain phenotypic variation, using experiments conducted with a baculovirus that infects gypsy moth (Lymantria dispar) larvae. We found that an empirically observed tradeoff between mean transmission rate and variation in transmission, which results from host heterogeneity, promotes long-term coexistence of two pathogen types in simulations of a population model. This tradeoff introduces an alternative strategy for the pathogen: a low-transmission, low-variability type can coexist with the high-transmission type favoured by classical non-heterogeneity models. In addi- tion, this tradeoff can help explain the extensive phenotypic variation we observed in field-col- lected pathogen isolates, in traits affecting virus fitness including transmission and environmental persistence. Similar heterogeneity tradeoffs might be a general mechanism promoting phenotypic variation in any pathogen for which hosts vary continuously in susceptibility.  +
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Phytoplankton are key components of aquatic ecosystems, fixing CO2 from the atmosphere through photosynthesis and supporting secondary production, yet relatively little is known about how future global warming might alter their biodiversity and associated ecosystem functioning. Here, we explore how the structure, function, and biodiversity of a planktonic metacommunity was altered after five years of experimental warming. Our outdoor mesocosm experiment was open to natural dispersal from the regional species pool, allowing us to explore the effects of experimental warming in the context of metacommunity dynamics. Warming of 4°C led to a 67% increase in the species richness of the phytoplankton, more evenly-distributed abundance, and higher rates of gross primary productivity. Warming elevated productivity indirectly, by increasing the biodiversity and biomass of the local phytoplankton communities. Warming also systematically shifted the taxonomic and functional trait composition of the phytoplankton, favoring large, colonial, inedible phytoplankton taxa, suggesting stronger top-down control, mediated by zooplankton grazing played an important role. Overall, our findings suggest that temperature can modulate species coexistence, and through such mechanisms, global warming could, in some cases, increase the species richness and productivity of phytoplankton communities.  +
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Pollination systems are recognized as critical for the maintenance of biodiversity in terrestrial ecosystems. Therefore, the understanding of mechanisms that promote the integrity of those mutualistic assemblages is an important issue for the conservation of biodiversity and ecosystem function. In this study we present a new population dynamics model for plant–pollinator interactions that is based on the consumer–resource approach and incorporates a few essential features of pollination ecology. The model was used to project the temporal dynamics of three empirical pollination network, in order to analyze how adaptive foraging of pollinators (AF) shapes the outcome of community dynamics in terms of biodiversity and network robustness to species loss. We found that the incorporation of AF into the dynamics of the pollination networks increased the persistence and diversity of its constituent species, and reduced secondary extinctions of both plants and animals. These findings were best explained by the following underlying processes: 1) AF increased the amount of floral resources extracted by specialist pollinators, and 2) AF raised the visitation rates received by specialist plants. We propose that the main mechanism by which AF enhanced those processes is (trophic) niche partitioning among animals, which in turn generates (pollen vector) niche partitioning among plants. Our results suggest that pollination networks can maintain their stability and diversity by the adaptive foraging of generalist pollinators.  +
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Predictions of how a population will respond to a selective pressure are valuable, especially in the case of infectious diseases, which often adapt to the interventions we use to control them. Yet attempts to predict how pathogen populations will change, for example in response to vaccines, are challenging. Such has been the case with Streptococcus pneumoniae , an important human colonizer and pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use recent advances in knowledge of negative-frequency dependent selection (NFDS) acting on frequencies of accessory genes (i.e., flexible genome) to predict the changes in the pneumococcal population after intervention. Implementing a deterministic NFDS model using the replicator equation, we can accurately predict which pneumococcal lineages will increase after intervention. Analyzing a population genomic sample of pneumococci collected before and after vaccination, we find that the predicted fitness of a lineage post-vaccine is significantly and positively correlated with the observed change in its prevalence. Then, using quadratic programming to numerically solve the frequencies of non-vaccine type lineages that best restored the pre-vaccine accessory gene frequencies, we accurately predict the post-vaccine population composition. Additionally, we also test the predictive ability of frequencies of core genome loci, a subset of metabolic loci, and naive estimates of prevalence change based on pre-vaccine lineages frequencies. Finally, we show how this approach can assess the migration and invasion capacity of emerging lineages, on the basis of their accessory genome. In general, we provide a method for predicting the impact of an intervention on pneumococcal populations and other bacterial pathogens for which NFDS is a main driving force.  +
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Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring in vivo biochemical parameters is difficult, and collectively fitting them to other experimental data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a "sloppy" spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our growth-factor-signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.  +
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Recent results have shown that deep neural networks (DNN) may have significant potential to serve as quantitatively precise models of sensory cortex neural populations. However, the implications these results have for our conceptual understanding of neural mechanisms are subtle. This is because many modern DNN brain models are best understood as the products of task-constrained optimization processes, unlike the intuitively simpler hand-crafted models from earlier approaches. In this chapter, we illustrate these issues by first discussing the nature of information processing in the primate ventral visual pathway, and review results comparing the response properties of units in goal-optimized DNN models to neural responses found throughout the ventral pathway. We then show how DNN visual system models are just one instance of a more general optimization framework whose logic may be applicable to understanding the underlying constraints that shape neural mechanisms throughout the brain. An important part of a scientist's job is to answer "why" questions. For cognitive neuroscientists, a core objective is to uncover the underlying reasons why the structures of the human brain are as they are. Since brains are biological systems, answering such questions is ultimately a matter of identifying the evolutionary and developmental constraints that shape brain structure and function. Such constraints are in part architectural: what large-scale brain structures are put in place genetically to help a brain help its host organism better meet evolutionary challenges? In light of the centrality of behavior in understanding the brain, an ethological investigation is also indicated: what behavioral goals most strongly constrain a given neural system? And since many complex behaviors in higher organisms are not entirely genetically determined and must instead be partly derived through experience of the world, a core question of learning is also involved: how do learning rules that absorb experiential data constrain what brains look like? The interactions between architectural structure, behavioral goals, and learning rules suggest a quantitative optimization framework as one route toward answering these "why" questions. Put simply, this means: postulating one or several goal behavior(s) as driving the evolution and/or development of a neural system of interest; finding architecturally plausible computational models that (attempt to) optimize for the behavior; and then quantitatively comparing the internal structures arrived at in the optimized models to measurements from large-scale neuroscience experiments. To the extent that there is a match between optimized models and the real data that is very substantially better than that found for various controls (e.g. models designed by hand or optimized for other tasks), this is evidence that something important has been understood about the underlying constraints that shape the brain system under investigation. Though it might sound challenging to put this approach into practice, recent successes suggest we might add to our list of maxims the observation that nothing in computational cognitive neuroscience makes sense except in light of optimization.  
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Research on the brain basis of speech and language faces theoretical and empirical challenges. Most current research, dominated by imaging, deficit-lesion, and electrophysiological techniques, seeks to identify regions that underpin aspects of language processing such as phonology, syntax, or semantics. The emphasis lies on localization and spatial characterization of function. The first part of the paper deals with a practical challenge that arises in the context of such a research programme. This maps problem concerns the extent to which spatial information and localization can satisfy the explanatory needs for perception and cognition. Several areas of investigation exemplify how the neural basis of speech and language is discussed in those terms (regions, streams, hemispheres, networks). The second part of the paper turns to a more troublesome challenge, namely how to formulate the formal links between neurobiology and cognition. This principled problem thus addresses the relation between the primitives of cognition (here speech, language) and neurobiology. Dealing with this mapping problem invites the development of linking hypotheses between the domains. The cognitive sciences provide granular, theoretically motivated claims about the structure of various domains (the "cognome"); neurobiology, similarly, provides a list of the available neural structures. However, explanatory connections will require crafting of computationally explicit linking hypotheses at the right level of abstraction. For both the practical maps problem and the principled mapping problem, developmental approaches and evidence can play a central role in the resolution. © 2012 Copyright Psychology Press.  +
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Sleep is crucial for daytime functioning, cognitive performance and general well-being. These aspects of daily life are known to be impaired after extended wake, yet, the underlying neuronal correlates have been difficult to identify. Accumulating evidence suggests that normal functioning of the brain is characterized by long-range temporal correlations (LRTCs) in cortex, which are supportive for decision-making and working memory tasks. Here we assess LRTCs in resting state human EEG data during a 40-hour sleep deprivation experiment by evaluating the decay in autocorrelation and the scaling exponent of the detrended fluctuation analysis from EEG amplitude fluctuations. We find with both measures that LRTCs decline as sleep deprivation progresses. This decline becomes evident when taking changes in signal power into appropriate consideration. Our results demonstrate the importance of sleep to maintain LRTCs in the human brain. In complex networks, LRTCs naturally emerge in the vicinity of a critical state. The observation of declining LRTCs during wake thus provides additional support for our hypothesis that sleep reorganizes cortical networks towards critical dynamics for optimal functioning.  +
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Starting with Darwin, biologists have asked how populations evolve from a low fitness state that is evolutionarily stable to a high fitness state that is not. Specifically of interest is the emergence of cooperation and multicellularity where the fitness of individuals often appears in conflict with that of the population. Theories of social evolution and evolutionary game theory have produced a number of fruitful results employing two-state two-body frameworks. In this study, we depart from this tradition and instead consider a multi-player, multi-state evolutionary game, in which the fitness of an agent is determined by its relationship to an arbitrary number of other agents. We show that populations organize themselves in one of four distinct phases of interdependence depending on one parameter, selection strength. Some of these phases involve the formation of specialized large-scale structures. We then describe how the evolution of independence can be manipulated through various external perturbations.  +
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Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associationa of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.  +
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The accumulation of data on the genomic bases of adaptation has triggered renewed interest in theoretical models of adaptation. Among these models, Fisher's geometric model (FGM) has received a lot of attention over the past two decades. FGM is based on a continuous multidimensional phenotypic landscape, but it is mostly used for the emerging properties of individual mutation effects. Despite its apparent simplicity and limited number of pa-rameters, FGM integrates a full model of mutation and epistatic interactions that allows the study of both beneficial and deleterious mutations and, subse-quently, the fate of evolving populations. In this review, I present the different properties of FGM and the qualitative and quantitative support they have received from experimental evolution data. I then discuss how to estimate the different parameters of the model and outline some future directions to connect FGM and the molecular determinants of adaptation.  +
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The brain comprises complex structural and functional networks, but much remains to be determined regarding how these networks support the communication processes that underlie neuronal computation. In this Review, Avena-Koenigsberger, Misic and Sporns discuss the network basis of communication dynamics in the brain.  +
S
The diversification of life involved enormous increases in size and complexity. The evolutionary transitions from prokaryotes to unicellular eukaryotes to metazoans were accompanied by major innovations in metabolic design. Here we show that the scalings of metabolic rate, population growth rate, and production efficiency with body size have changed across the evolutionary transitions. Metabolic rate scales with body mass superlinearly in prokaryotes, linearly in protists, and sublinearly in metazoans, so Kleiber's 3/4 power scaling law does not apply universally across organisms. The scaling of maximum population growth rate shifts from positive in prokaryotes to negative in protists and metazoans, and the efficiency of production declines across these groups. Major changes in metabolic processes during the early evolution of life overcame existing constraints, exploited new opportunities, and imposed new constraints.  +
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The geometric mean of fitness is considered to be the main indicator of evolutionary change in stochastic models. However, this measure was initially derived for models with infinite population sizes, where the long-term evolutionary behavior can be described with certainty. In this paper we begin an exploration of the limitations and utility of this approach to evolution in finite populations and discuss alternate methods for predicting evolutionary dynamics. We reanalyze a model of lottery competition under environmental stochasticity by including population finiteness, and show that the geometric mean predictions do not always agree with those based on the fixa- tion probability of rare alleles. Further, the fixation probability can be inserted into adaptive dynamics equations to derive the mean state of the population. We explore the effects of increasing population size on these conclusions through simulations. These simulations show that for small population sizes the fixation probability accurately predicts the course of evolution, but as population size becomes large the geometric mean predictions are upheld. The two approaches are reconciled because the time scale on which the fixation probability approach applies becomes very large as population size grows.  +
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The interspecies exchange of metabolites plays a key role in the spatiotemporal dynamics of microbial communities. This raises the question of whether ecosystem-level behavior of structured communities can be predicted using genome-scale metabolic models for multiple organisms. We developed a modeling framework that integrates dynamic flux balance analysis with diffusion on a lattice and applied it to engineered communities. First, we predicted and experimentally confirmed the species ratio to which a two-species mutualistic consortium converges and the equilibrium composition of a newly engineered three-member community. We next identified a specific spatial arrangement of colonies, which gives rise to what we term the "eclipse dilemma": does a competitor placed between a colony and its cross-feeding partner benefit or hurt growth of the original colony? Our experimentally validated finding that the net outcome is beneficial highlights the complex nature of metabolic interactions in microbial communities while at the same time demonstrating their predictability. © 2014 The Authors.  +
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The meaning of language is represented in regions of the cerebral cortex collectively known as the ‘semantic system’. However, little of the semantic system has been mapped comprehensively, and the semantic selectivity of most regions is unknown. Here we systematically map semantic selectivity across the cortex using voxel-wise modelling of functional MRI (fMRI) data collected while subjects listened to hours of narrative stories. We show that the semantic system is organized into intricate patterns that seem to be consistent across individuals. We then use a novel generative model to create a detailed semantic atlas. Our results suggest that most areas within the semantic system represent information about specific semantic domains, or groups of related concepts, and our atlas shows which domains are represented in each area. This study demonstrates that data-driven methods—commonplace in studies of human neuroanatomy and functional connectivity—provide a powerful and efficient means for mapping functional representations in the brain.  +
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The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine. Gratton et al. comprehensively measure individual, day-to-day, and task variance in functional brain networks, revealing that networks are dominated by stable individual factors, not cognitive content. These findings suggest utility of functional network measurements in personalized medicine.  +
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The past twenty years have seen a resurgence of interest in nonequilibrium thermodynamics, thanks to advances in the theory of stochastic processes and in their thermodynamic interpretation. Fluctuation theorems provide fundamental constraints on the dynamics of systems arbitrarily far from thermal equilibrium. Thermodynamic uncertainty relations bound the dissipative cost of precision in a wide variety of processes. Concepts of excess work and excess heat provide the basis for a complete thermodynamics of nonequilibrium steady states, including generalized Clausius relations and thermodynamic potentials. But these general results carry their own limitations: fluctuation theorems involve exponential averages that can depend sensitively on unobservably rare trajectories; steady-state thermodynamics makes use of a dual dynamics that lacks any direct physical interpretation. This review aims to present these central results of contemporary nonequilibrium thermodynamics in such a way that the power of each claim for making physical predictions can be clearly assessed, using examples from current topics in soft matter and biophysics.  +