bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking local adaptation with the evolution of sex differences
Authors: Connallon Tim , Débarre Florence , Li Xiang-Yi 
Published: August 2018

Many conspicuous forms of evolutionary diversity occur within species. Two prominent examples include evolutionary divergence between populations differentially adapted to their local environments (local adaptation), and divergence between females and males in response to sex differences in selection (sexual dimorphismsensu lato). These two forms of diversity have inspired vibrant research programmes, yet these fields have largely developed in isolation from one another. Nevertheless, conceptual parallels between these research traditions are striking. Opportunities for local adaptation strike a balance between local selection, which promotes divergence, and gene flow—via dispersal and interbreeding between populations—which constrains it. Sex differences are similarly constrained by fundamental features of inheritance that mimic gene flow. Offspring of each sex inherit genes from same-sex and opposite-sex parents, leading to gene flow between each differentially selected half of the population, and raising the question of how sex differences arise and are maintained. This special issue synthesizes and extends emerging research at the interface between the research traditions of local adaptation and sex differences. Each field can promote understanding of the other, and interactions between local adaptation and sex differences can generate new empirical predictions about the evolutionary consequences of selection that varies across space, time, and between the sexes.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.
Sexual conflict in its ecological setting
Authors: Perry Jennifer C. , Rowe Locke 
Published: August 2018

Sexual conflict can lead to rapid and continuous coevolution between females and males, without any inputs from varying ecology. Yet both the degree of conflict and selection on antagonistic traits are known to be sensitive to local ecological conditions. This leads to the longstanding question: to what extent does variation in ecological context drive sexually antagonistic coevolution? In water striders, there is much information about the impacts of ecological factors on conflict, and about patterns of antagonistic coevolution. However, the connection between the two is poorly understood. Here, we first review the multiple ways in which ecological context might affect the coevolutionary trajectory of the sexes. We then review ecological and coevolutionary patterns in water striders, and connections between them, in light of theory and new data. Our analysis suggests that ecological variation does impact observed patterns of antagonistic coevolution, but highlights significant uncertainty due to the multiple pathways by which ecological factors can influence conflict and its evolutionary outcome. To the extent that water striders are a reasonable reflection of other systems, this observation serves as both an opportunity and a warning: there is much to learn, but gaining insight may be a daunting process in many systems.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences'.
Hybridization, sex-specific genomic architecture and local adaptation
Authors: Runemark Anna , Eroukhmanoff Fabrice , Nava-Bolaños Angela , Hermansen Jo S. , Meier Joana I. 
Published: August 2018

While gene flow can reduce the potential for local adaptation, hybridization may conversely provide genetic variation that increases the potential for local adaptation. Hybridization may also affect adaptation through altering sexual dimorphism and sexual conflict, but this remains largely unstudied. Here, we discuss how hybridization may affect sexual dimorphism and conflict due to differential effects of hybridization on males and females, and then how this, in turn, may affect local adaptation. First, in species with heterochromatic sexes, the lower viability of the heterogametic sex in hybrids could shift the balance in sexual conflict. Second, sex-specific inheritance of the mitochondrial genome in hybrids may lead to cytonuclear mismatches, for example, in the form of ‘mother's curse’, with potential consequences for sex ratio and sex-specific expression. Third, sex-biased introgression and recombination may lead to sex-specific consequences of hybridization. Fourth, transgressive segregation of sexually antagonistic alleles could increase sexual dimorphism in hybrid populations. Sexual dimorphism can reduce sexual conflict and enhance intersexual niche partitioning, increasing the fitness of hybrids. Adaptive introgression of alleles reducing sexual conflict or enhancing intersexual niche partitioning may facilitate local adaptation, and could favour the colonization of novel habitats. We review these consequences of hybridization on sex differences and local adaptation, and discuss how their prevalence and importance could be tested empirically.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences'.
Genetic constraints on microevolutionary divergence of sex-biased gene expression
Authors: Allen Scott L. , Bonduriansky Russell , Chenoweth Stephen F. 
Published: August 2018

The evolution of sex-specific phenotypes is an important dimension of diversification and local adaptation. The sex-dependent regulation of gene expression is considered a key genomic mechanism facilitating sex-dependent adaptation. In many species, genes with male-biased expression evolve faster in DNA sequence and expression level than genes with female-biased or sexually monomorphic expression. While positive selection may be responsible for rapid DNA sequence evolution, why expression of male-biased genes also evolves rapidly remains unclear. Beyond sex differences in selection, some aspects of the genetic architecture of gene expression could contribute to the rapid evolution of male-biased gene expression. First, male-biased genes might simply have greater standing genetic variance than female-biased genes. Second, male-biased genes could be less constrained by pleiotropy, either within or between sexes. Here, we evaluate these alternative explanations on an intraspecific scale using a series of quantitative genetic experiments conducted on natural variation in male and female gene expression in the flyDrosophila serrata. Male-biased genes had significantly higher genetic variance than female-biased genes and were generally more narrowly expressed across tissues, suggesting lower within-individual pleiotropy. However, consistent with stronger constraints due to between-sex pleiotropy, their between-sex genetic correlations,rMF, were higher than for female-biased genes and more strongly negatively associated with sex bias. Using an extensive clinal dataset, we tested whether sex differences in gene expression divergence among populations have been shaped by pleiotropy.Here too, male-biased gene divergence was more strongly associated with between-sex pleiotropy than was female-biased gene divergence. Systematic differences in genetic variance and pleiotropy may be important factors influencing sex-specific adaptation arising through changes in gene expression.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.
Linking sex differences to the evolution of infectious disease life-histories
Authors: Hall Matthew D. , Mideo Nicole 
Published: August 2018

Sex differences in the prevalence, course and severity of infection are widespread, yet the evolutionary consequences of these differences remain unclear. Understanding how male–female differences affect the trajectory of infectious disease requires connecting the contrasting dynamics that pathogens might experience within each sex to the number of susceptible and infected individuals that are circulating in a population. In this study, we build on theory using genetic covariance functions to link the growth of a pathogen within a host to the evolution and spread of disease between individuals. Using theDaphnia–Pasteuriasystem as a test case, we show that on the basis of within-host dynamics alone, females seem to be more evolutionarily liable for the pathogen, with higher spore loads and greater divergence among pathogen genotypes as infection progresses. Between-host transmission, however, appears to offset the lower performance of a pathogen within a male host, making even subtle differences between the sexes evolutionarily relevant, as long as the selection generated by the between-host dynamics is sufficiently strong. Our model suggests that relatively simple differences in within-host processes occurring in males and females can lead to complex patterns of genetic constraint on pathogen evolution, particularly during an expanding epidemic.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.
Three-Dimensional Histology of Whole Zebrafish by Sub-Micron Synchrotron X-ray Micro-Tomography
Authors: Ding Yifu , Vanselow Daniel J. , Yakovlev Maksim A. , Katz Spencer R. , Lin Alex Y. , Clark Darin P. , Vargas Phillip , Xin Xuying , Copper Jean E. , Canfield Victor A. , Ang Khai C. , Wang Yuxin , Xiao Xianghui , Carlo Francesco De , Rossum Damian B. van , Rivière Patrick La , Cheng Keith C. 
Published: August 2018

AbstractHistological studies providing cellular insights into tissue architecture have been central to biological discovery and remain clinically invaluable today. Extending histology to three dimensions would be transformational for research and diagnostics. However, three-dimensional histology is impractical using current techniques. We have customized sample preparation, synchrotron X-ray tomographic parameters, and three-dimensional image analysis to allow for complete histological phenotyping using whole larval and juvenile zebrafish. The resulting digital zebrafish can be virtually sectioned and visualized in any plane. Whole-animal reconstructions at subcellular resolution also enable computational characterization of the zebrafish nervous system by region-specific detection of cell nuclei and quantitative assessment of individual phenotypic variation. Three-dimensional histological phenotyping has potential use in genetic and chemical screens, and in clinical and toxicological tissue diagnostics.One Sentence SummarySynchrotron X-ray micro-tomography can be used to rapidly create 3-dimensional images of fixed and stained specimens without sectioning, enabling computational histological phenotyping at cellular resolution.
HTSlib-js: Developer toolkit for a client-side JavaScript interface for HTSlib
Authors: Park Jeongbin , Childs Liam H. , Schlesner Matthias , Eils Roland 
Published: August 2018

AbstractBackgroundAn increasing number of bioinformatics tools are developed in JavaScript to provide an interactive visual interface to users. However, there are no tools yet that enable fast client-side analysis of large, high-throughput sequencing file formats, such as BAM and VCF files.ResultsWe present HTSlib-js, an asm.js-based JavaScript wrapper for HTSlib, the de facto standard for processing BAM and VCF files. HTSlib-js exploits recent technological advances in web browser engines that dramatically increase the performance of browser-based tools to enable swift processing of files in the aforementioned formats. HTSlib-js enables quick development of JavaScript-based applications that include processing of aligned sequence reads and variant calling data.ConclusionsHTSlib-js constitutes a toolkit for developers to easily write fast, accessible, browser-based applications that place an emphasis on data visualization, interactivity and privacy. Real-world examples demonstrate the capabilities of HTSlib-js and serve as guide for own developments.
SWI/SNF chromatin remodeling controls Notch-responsive enhancer accessibility
Authors: Pillidge Zoe , Bray Sarah J 
Published: August 2018

AbstractNotch signaling plays a key role in many cell fate decisions during development by directing different gene expression programs via the transcription factor CSL, known as Su(H) inDrosophila.Which target genes are responsive to Notch signaling is influenced by the chromatin state of enhancers, yet how this is regulated is not fully known. Detecting an increase in the histone variant H3.3 in response to Notch signaling, we tested which chromatin remodelers or histone chaperones were required for the changes in enhancer accessibility to Su(H) binding. This revealed a crucial role for the Brahma SWI/SNF chromatin remodeling complex in conferring enhancer accessibility and enabling the transcriptional response. The Notch-responsive regions had high levels of nucleosome turnover which were dependent on the Brahma complex, increased with Notch signaling and primarily involved histone H3.3. Together these results highlight the importance of SWI/SNF-mediated nucleosome turnover in rendering enhancers responsive to Notch.
Whole genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes
Authors: Lucas Eric R. , Miles Alistair , Harding Nicholas J. , Clarkson Chris S. , N. Lawniczak Mara K. , Kwiatkowski Dominic P. , Weetman David , Donnelly Martin J. ,   The Anopheles gambiae 1000 Genomes Consortium
Published: August 2018

AbstractBackgroundPolymorphisms in the copy number of a genetic region can influence gene expression, coding sequence and zygosity, making them powerful actors in the evolutionary process. Copy number variants (CNVs) are however understudied, being more difficult to detect than single nucleotide polymorphisms. We take advantage of the intense selective pressures on the major malaria vector Anopheles gambiae, caused by the widespread use of insecticides for malaria control, to investigate the role of CNVs in the evolution of insecticide resistance.ResultsUsing the whole-genome sequencing data from 1142 samples in the An. gambiae 1000 genomes project, we identified 1557 independent increases in copy number, encompassing a total of 267 genes, which were enriched for gene families linked to metabolic insecticide resistance. The five major candidate genes for metabolic resistance were all found in at least one CNV, and were often the target of multiple independent CNVs, reaching as many as 16 CNVs in Cyp9k1. These CNVs have furthermore been spreading due to positive selection, indicated by high local CNV frequencies and extended haplotype homozygosity.ConclusionsOur results demonstrate the importance of CNVs in the response to selection, with CNVs being closely associated with genes involved in the evolution of resistance to insecticides, highlighting the urgent need to identify their relative contributions to resistance and to track their spread as the application of insecticide in malaria endemic countries intensifies. Our detailed descriptions of CNVs found across the species range provides the tools to do so.
Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats
Authors: Varlinskaya Elena I. , Spear Linda Patia , Diaz Marvin R. 
Published: August 2018

AbstractThe dynorphin/kappa (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adults, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development.
Gene-Specific Predictability of Protein Levels from mRNA Data in Humans
Authors: Moulana Alief , Scanteianu Adriana , Jones DeAnalisa , Stern Alan D. , Bouhaddou Mehdi , Birtwistle Marc R. 
Published: August 2018

AbstractTranscriptomic data are widely available, and the extent to which they are predictive of protein abundances remains debated. Using multiple public databases, we calculate mRNA and mRNA-to-protein ratio variability across human tissues to quantify and classify genes for protein abundance predictability confidence. We propose that such predictability is best understood as a spectrum. A gene-specific, tissue-independent mRNA-to-protein ratio plus mRNA levels explains ∼80% of protein abundance variance for more predictable genes, as compared to ∼55% for less predictable genes. Protein abundance predictability is consistent with independent mRNA and protein data from two disparate cell lines, and mRNA-to-protein ratios estimated from publicly-available databases have predictive power in these independent datasets. Genes with higher predictability are enriched for metabolic function, tissue development/cell differentiation roles, and transmembrane transporter activity. Genes with lower predictability are associated with cell adhesion, motility and organization, the immune system, and the cytoskeleton. Surprisingly, many genes that regulate mRNA-to-protein ratios are constitutively expressed but also exhibit ratio variability, suggesting a general autoregulation mechanism whereby protein expression profile changes can be implemented quickly, or homeostatic sensing stabilizes protein abundances under fluctuating conditions. Gene classifications and their mRNA-to-protein ratios are provided as a resource to facilitate protein abundance predictions by others.
A heterogeneous spatial model in which savanna and forest coexist in a stable equilibrium
Authors: Durrett Rick , Ma Ruibo 
Published: August 2018

AbstractIn work with a variety of co-authors, Staver and Levin have argued that savanna and forest coexist as alternative stable states with discontinuous changes in density of trees at the boundary. Here we formulate a nonhomogeneous spatial model of the competition between forest and savanna. We prove that coexistence occurs for a time that is exponential in the size of the system, and that after an initial transient, boundaries between the alternative equilibria remain stable.
The Mycobacterium tuberculosis Phosphate-Sensing Pst/SenX3-RegX3 System Regulates ESX-5 Secretion to Evade Host Immunity
Authors: Elliott Sarah R. , White Dylan W. , Tischler Anna D. 
Published: August 2018

ABSTRACTThe Mycobacterium tuberculosis Type VII secretion system ESX-5, which has been implicated in virulence, is activated at the transcriptional level by the phosphate starvation responsive Pst/SenX3-RegX3 signal transduction system. Deletion of pstA1, which encodes a Pst phosphate transporter component, causes constitutive activation of the response regulator RegX3, hyper-secretion of ESX-5 substrates and attenuation in the mouse infection model. We hypothesized that constitutive activation of ESX-5 secretion causes attenuation of the ΔpstA1 mutant. To test this, we uncoupled ESX-5 from regulation by RegX3. Using electrophoretic mobility shift assays, we defined a RegX3 binding site in the esx-5 locus. Deletion or mutation of the RegX3 binding site reversed hyper-secretion of the ESX-5 substrate EsxN by the ΔpstA1 mutant and abrogated induction of EsxN secretion in response to phosphate limitation by wild-type M. tuberculosis. Deletion of the esx-5 RegX3 binding site (ΔBS) suppressed attenuation of the ΔpstA1 mutant in Irgm1-/- mice, suggesting that constitutive ESX-5 secretion limits M. tuberculosis evasion of host immune responses that are independent of Irgm1. However, the ΔpstA1ΔBS mutant remained attenuated in both NOS2-/- and C57BL/6 mice, suggesting that factors other than ESX-5 secretion also contribute to attenuation of the ΔpstA1 mutant. In addition, a ΔpstA1ΔesxN mutant lacking the hyper-secreted ESX-5 substrate EsxN remained attenuated in Irgm1-/- mice, suggesting that ESX-5 substrates other than EsxN cause increased susceptibility to host immunity. Our data indicate that while M. tuberculosis requires ESX-5 for virulence, it tightly controls secretion of ESX-5 substrates to avoid elimination by host immune responses.
Education, intelligence and Alzheimer’s disease: Evidence from a multivariable two-sample Mendelian randomization study
Authors: Anderson Emma L , Howe Laura D , Wade Kaitlin H , Ben-Shlomo Yoav , Hill W. David , Deary Ian J , Sanderson Eleanor C , Zheng Jie , Korologou-Linden Roxanna , Stergiakouli Evie , Smith George Davey , Davies Neil M , Hemani Gibran 
Published: August 2018

AbstractObjectivesTo examine whether educational attainment and intelligence have causal effects on risk of Alzheimer’s disease (AD), independently of each other.DesignTwo-sample univariable and multivariable Mendelian Randomization (MR) to estimate the causal effects of education on intelligence and vice versa, and the total and independent causal effects of both education and intelligence on risk of AD.Participants17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer’s Project (IGAP) consortiumMain outcome measureOdds ratio of AD per standardised deviation increase in years of schooling and intelligenceResultsThere was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions. Similar overall effects were observed for both educational attainment and intelligence on AD risk in the univariable MR analysis; with each SD increase in years of schooling and intelligence, odds of AD were, on average, 37% (95% CI: 23% to 49%) and 35% (95% CI: 25% to 43%) lower, respectively. There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account, but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis.ConclusionsThere is robust evidence for an independent, causal effect of intelligence in lowering AD risk, potentially supporting a role for cognitive training interventions to improve aspects of intelligence. However, given the observed causal effect of educational attainment on intelligence, there may also be support for policies aimed at increasing length of schooling to lower incidence of AD.