Kierkegaard and Optical Linguistics

Kierkegaard and Optical Linguistic

Pervasive Hitchhiking at Coding and Regulatory Sites in Humans

Much effort and interest have focused on assessing the importance of natural selection, particularly positive natural selection, in shaping the human genome. Although scans for positive selection have identified candidate loci that may be associated with positive selection in humans, such scans do not indicate whether adaptation is frequent in general in humans. Studies based on the reasoning of the MacDonald–Kreitman test, which, in principle, can be used to evaluate the extent of positive selection, suggested that adaptation is detectable in the human genome but that it is less common than in Drosophila or Escherichia coli. Both positive and purifying natural selection at functional sites should affect levels and patterns of polymorphism at linked nonfunctional sites. Here, we search for these effects by analyzing patterns of neutral polymorphism in humans in relation to the rates of recombination, functional density, and functional divergence with chimpanzees. We find that the levels of neutral polymorphism are lower in the regions of lower recombination and in the regions of higher functional density or divergence. These correlations persist after controlling for the variation in GC content, density of simple repeats, selective constraint, mutation rate, and depth of sequencing coverage. We argue that these results are most plausibly explained by the effects of natural selection at functional sites—either recurrent selective sweeps or background selection—on the levels of linked neutral polymorphism. Natural selection at both coding and regulatory sites appears to affect linked neutral polymorphism, reducing neutral polymorphism by 6% genome-wide and by 11% in the gene-rich half of the human genome. These findings suggest that the effects of natural selection at linked sites cannot be ignored in the study of neutral human polymorphism

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

Is there an association between seeing incidents of alcohol or drug use in films and young Scottish adults' own alcohol or drug use? A cross sectional study

<p>Background: As the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images of certain behaviours in films are associated with uptake of those behaviours in young people. Associations have been reported between exposure to smoking images in films and smoking initiation, and between exposure to film alcohol images and initiation of alcohol consumption, in younger adolescents in the USA and Germany. To date no studies have reported on film images of recreational drug use and young people's own drug use.</p> <p>Methods: Cross sectional multivariable logistic regression analysis of data collected at age 19 (2002-4) from a cohort of young people (502 boys, 500 girls) previously surveyed at ages 11 (in 1994-5), 13 and 15 in schools in the West of Scotland. Outcome measures at age 19 were: exceeding the 'sensible drinking' guidelines ('heavy drinkers') and binge drinking (based on alcohol consumption reported in last week), and ever use of cannabis and of 'hard' drugs. The principle predictor variables were an estimate of exposure to images of alcohol, and of drug use, in films, controlling for factors related to the uptake of substance use in young people.</p> <p>Results: A third of these young adults (33%) were classed as 'heavy drinkers' and half (47%) as 'binge drinkers' on the basis of their previous week's consumption. Over half (56%) reported ever use of cannabis and 13% ever use of one or more of the 'hard' drugs listed. There were linear trends in the percentage of heavy drinkers (p = .018) and binge drinkers (p = 0.012) by film alcohol exposure quartiles, and for ever use of cannabis by film drug exposure (p = .000), and for ever use of 'hard' drugs (p = .033). The odds ratios for heavy drinking (1.56, 95% CI 1.06-2.29 comparing highest with lowest quartile of film alcohol exposure) and binge drinking (1.59, 95% CI 1.10-2.30) were attenuated by adjustment for gender, social class, family background (parental structure, parental care and parental control), attitudes to risk-taking and rule-breaking, and qualifications (OR heavy drinking 1.42, 95% CI 0.95-2.13 and binge drinking 1.49, 95% CI 1.01-2.19), and further so when adjusting for friends' drinking status (when the odds ratios were no longer significant). A similar pattern was seen for ever use of cannabis and 'hard' drugs (unadjusted OR 1.80, 95% CI 1.24-2.62 and 1.57, 95% CI 0.91-2.69 respectively, 'fully' adjusted OR 1.41 (0.90-2.22 and 1.28 (0.66-2.47) respectively).</p> <p>Conclusions: Despite some limitations, which are discussed, these cross-sectional results add to a body of work which suggests that it is important to design good longitudinal studies which can determine whether exposure to images of potentially health-damaging behaviours lead to uptake of these behaviours during adolescence and early adulthood, and to examine factors that might mediate this relationship.</p&gt

A Conserved Supergene Locus Controls Colour Pattern Diversity in Heliconius Butterflies

We studied whether similar developmental genetic mechanisms are involved in both convergent and divergent evolution. Mimetic insects are known for their diversity of patterns as well as their remarkable evolutionary convergence, and they have played an important role in controversies over the respective roles of selection and constraints in adaptive evolution. Here we contrast three butterfly species, all classic examples of Müllerian mimicry. We used a genetic linkage map to show that a locus, Yb, which controls the presence of a yellow band in geographic races of Heliconius melpomene, maps precisely to the same location as the locus Cr, which has very similar phenotypic effects in its co-mimic H. erato. Furthermore, the same genomic location acts as a “supergene”, determining multiple sympatric morphs in a third species, H. numata. H. numata is a species with a very different phenotypic appearance, whose many forms mimic different unrelated ithomiine butterflies in the genus Melinaea. Other unlinked colour pattern loci map to a homologous linkage group in the co-mimics H. melpomene and H. erato, but they are not involved in mimetic polymorphism in H. numata. Hence, a single region from the multilocus colour pattern architecture of H. melpomene and H. erato appears to have gained control of the entire wing-pattern variability in H. numata, presumably as a result of selection for mimetic “supergene” polymorphism without intermediates. Although we cannot at this stage confirm the homology of the loci segregating in the three species, our results imply that a conserved yet relatively unconstrained mechanism underlying pattern switching can affect mimicry in radically different ways. We also show that adaptive evolution, both convergent and diversifying, can occur by the repeated involvement of the same genomic regions

Identification of a sex-linked SNP marker in the salmon louse (Lepeophtheirus salmonis) using RAD sequencing

The salmon louse (Lepeophtheirus salmonis (Krøyer, 1837)) is a parasitic copepod that can, if untreated, cause considerable damage to Atlantic salmon (Salmo salar Linnaeus, 1758) and incurs significant costs to the Atlantic salmon mariculture industry. Salmon lice are gonochoristic and normally show sex ratios close to 1:1. While this observation suggests that sex determination in salmon lice is genetic, with only minor environmental influences, the mechanism of sex determination in the salmon louse is unknown. This paper describes the identification of a sex-linked Single Nucleotide Polymorphism (SNP) marker, providing the first evidence for a genetic mechanism of sex determination in the salmon louse. Restriction site-associated DNA sequencing (RAD-seq) was used to isolate SNP markers in a laboratory-maintained salmon louse strain. A total of 85 million raw Illumina 100 base paired-end reads produced 281,838 unique RAD-tags across 24 unrelated individuals. RAD marker Lsa101901 showed complete association with phenotypic sex for all individuals analysed, being heterozygous in females and homozygous in males. Using an allele-specific PCR assay for genotyping, this SNP association pattern was further confirmed for three unrelated salmon louse strains, displaying complete association with phenotypic sex in a total of 96 genotyped individuals. The marker Lsa101901 was located in the coding region of the prohibitin-2 gene, which showed a sex-dependent differential expression, with mRNA levels determined by RT-qPCR about 1.8-fold higher in adult female than adult male salmon lice. This study's observations of a novel sex-linked SNP marker are consistent with sex determination in the salmon louse being genetic and following a female heterozygous system. Marker Lsa101901 provides a tool to determine the genetic sex of salmon lice, and could be useful in the development of control strategies

A Polymorphism in the HLA-DPB1 Gene Is Associated with Susceptibility to Multiple Sclerosis

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association

The Effect of Inappropriate Calibration: Three Case Studies in Molecular Ecology

Time-scales estimated from sequence data play an important role in molecular ecology. They can be used to draw correlations between evolutionary and palaeoclimatic events, to measure the tempo of speciation, and to study the demographic history of an endangered species. In all of these studies, it is paramount to have accurate estimates of time-scales and substitution rates. Molecular ecological studies typically focus on intraspecific data that have evolved on genealogical scales, but often these studies inappropriately employ deep fossil calibrations or canonical substitution rates (e.g., 1% per million years for birds and mammals) for calibrating estimates of divergence times. These approaches can yield misleading estimates of molecular time-scales, with significant impacts on subsequent evolutionary and ecological inferences. We illustrate this calibration problem using three case studies: avian speciation in the late Pleistocene, the demographic history of bowhead whales, and the Pleistocene biogeography of brown bears. For each data set, we compare the date estimates that are obtained using internal and external calibration points. In all three cases, the conclusions are significantly altered by the application of revised, internally-calibrated substitution rates. Collectively, the results emphasise the importance of judicious selection of calibrations for analyses of recent evolutionary events

Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse

A finished clone-based assembly of the mouse genome reveals extensive recent sequence duplication during recent evolution and rodent-specific expansion of certain gene families. Newly assembled duplications contain protein-coding genes that are mostly involved in reproductive function

The determinants of genetic diversity in butterflies

This is the final version. Available on open access from Nature Research via the DOI in this recordUnder the neutral theory, genetic diversity is expected to increase with population size. While comparative analyses have consistently failed to find strong relationships between census population size and genetic diversity, a recent study across animals identified a strong correlation between propagule size and genetic diversity, suggesting that r-strategists that produce many small offspring, have greater long-term population sizes. Here we compare genome-wide genetic diversity across 38 species of European butterflies (Papilionoidea), a group that shows little variation in reproductive strategy. We show that genetic diversity across butterflies varies over an order of magnitude and that this variation cannot be explained by differences in current abundance, propagule size, host or geographic range. Instead, neutral genetic diversity is negatively correlated with body size and positively with the length of the genetic map. This suggests that genetic diversity is determined both by differences in long-term population size and the elect of selection on linked sites.Biotechnology & Biological Sciences Research Council (BBSRC)European Research CouncilNatural Environmental Research Council (NERC)Institute of Evolutionary Biology at Edinburgh Universit