Recombining your way out of trouble: the genetic architecture of hybrid fitness under environmental stress

Hybridization between species is a fundamental evolutionary force that can both promote and delay adaptation. There is a deficit in our understanding of the genetic basis of hybrid fitness, especially in non-domesticated organisms. We also know little about how hybrid fitness changes as a function of environmental stress. Here, we made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species, exposed populations to ten toxins, and sequenced the most resilient hybrids on low coverage using ddRADseq. We expected to find strong negative epistasis and heterozygote advantage in the hybrid genomes. We investigated three aspects of hybridness: 1) hybridity, 2) interspecific heterozygosity, and 3) epistasis (positive or negative associations between non-homologous chromosomes). Linear mixed effect models revealed strong genotype-by-environment interactions with many chromosomes and chromosomal interactions showing species-biased content depending on the environment. Against our predictions, we found extensive selection against heterozygosity such that homozygous allelic combinations from the same species were strongly overrepresented in an otherwise hybrid genomic background. We also observed multiple cases of positive epistasis between chromosomes from opposite species, confirmed by epistasis- and selection-free simulations, which is surprising given the large divergence of the parental species (~15% genome-wide). Together, these results suggest that stress-resilient hybrid genomes can be assembled from the best features of both parents, without paying high costs of negative epistasis across large evolutionary distances. Our findings illustrate the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of hybrid populations

Thermodynamics of the L\'evy spin glass

We investigate the L\'evy glass, a mean-field spin glass model with power-law distributed couplings characterized by a divergent second moment. By combining extensively many small couplings with a spare random backbone of strong bonds the model is intermediate between the Sherrington-Kirkpatrick and the Viana-Bray model. A truncated version where couplings smaller than some threshold \eps are neglected can be studied within the cavity method developed for spin glasses on locally tree-like random graphs. By performing the limit \eps\to 0 in a well-defined way we calculate the thermodynamic functions within replica symmetry and determine the de Almeida-Thouless line in the presence of an external magnetic field. Contrary to previous findings we show that there is no replica-symmetric spin glass phase. Moreover we determine the leading corrections to the ground-state energy within one-step replica symmetry breaking. The effects due to the breaking of replica symmetry appear to be small in accordance with the intuitive picture that a few strong bonds per spin reduce the degree of frustration in the system

Endo-cannibalism in the making of a recent British ancestor

Following his death in 1975, the ashes of Wally Hope, founder of Stonehenge People's Free Festival, were scattered in the centre of Stonehenge. When a child tasted the ashes the rest of the group followed this lead. In the following decades, as the festival increasingly became the site of contest about British heritage and culture, the story of Wally's ashes was told at significant times. His name continues to be invoked at gatherings today. This paper discusses these events as 'the making of an ancestor', and explores wider contexts in which they might be understood. These include Druidic involvement in the revival of cremation, Amazonian bone-ash endo-cannibalism, and popular means of speaking of and to dead relatives. In addition to considering the role of 'ancestors' in contemporary Britain, the paper contributes to considerations of 'ancestry' as a different way of being dead, of a particular moment in the evolution of an alternative religious neo-tribal movement, of the meanings of 'cannibalism', and of the ways in which human remains might be treated by the bereaved and by various other interested parties

Delayed trait development and the convergent evolution of shell kinesis in turtles

Developmental processes are foundational to clarifying the causes of convergent evolution. Here, we show how a key convergently evolving trait is slowly “acquired” in growing turtles. Adaptive morphological change tends to originate late in turtle ontogeny, owing to design constraints imposed by the shell. We investigated this trend by examining derived patterns of shell formation associated with the multiple (≥ 8) origins of shell closure (kinesis) in smallbodied turtles. Using box turtles as a model, we demonstrate that the flexible hinge joint required for shell kinesis differentiates gradually and via extensive repatterning of shell tissue. Disproportionate changes in shell shape and size substantiate that this transformation is a delayed ontogenetic response (3-5 years post-hatching) to structural alterations that arise in embryogenesis. These findings exemplify that the translation of genotype to phenotype may reach far beyond embryonic life stages. Thus, the temporal scope for developmental origins of adaptive morphological change might be broader than generally understood. We propose that delayed trait differentiation via tissue repatterning might facilitate phenotypic diversification and innovation that otherwise would not arise due to developmental constraints

Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion and Contraction

Numerous F-actin containing structures are involved in regulating protrusion of membrane at the leading edge of motile cells. We have investigated the structure and dynamics of filopodia as they relate to events at the leading edge and the function of the trailing actin networks. We have found that although filopodia contain parallel bundles of actin, they contain a surprisingly nonuniform spatial and temporal distribution of actin binding proteins. Along the length of the actin filaments in a single filopodium, the most distal portion contains primarily T-plastin, while the proximal portion is primarily bound by α-actinin and coronin. Some filopodia are stationary, but lateral filopodia move with respect to the leading edge. They appear to form a mechanical link between the actin polymerization network at the front of the cell and the myosin motor activity in the cell body. The direction of lateral filopodial movement is associated with the direction of cell migration. When lateral filopodia initiate from and move toward only one side of a cell, the cell will turn opposite to the direction of filopodial flow. Therefore, this filopodia-myosin II system allows actin polymerization driven protrusion forces and myosin II mediated contractile force to be mechanically coordinated

Stability of the replica-symmetric saddle-point in general mean-field spin-glass models

Within the replica approach to mean-field spin-glasses the transition from ergodic high-temperature behaviour to the glassy low-temperature phase is marked by the instability of the replica-symmetric saddle-point. For general spin-glass models with non-Gaussian field distributions the corresponding Hessian is a $2^n\times 2^n$ matrix with the number $n$ of replicas tending to zero eventually. We block-diagonalize this Hessian matrix using representation theory of the permutation group and identify the blocks related to the spin-glass susceptibility. Performing the limit $n\to 0$ within these blocks we derive expressions for the de~Almeida-Thouless line of general spin-glass models. Specifying these expressions to the cases of the Sherrington-Kirkpatrick, Viana-Bray, and the L\'evy spin glass respectively we obtain results in agreement with previous findings using the cavity approach

GLP-1 Agonists in Type 1 Diabetes Mellitus: A Review of the Literature

Objective: To review the use of GLP-1 agonists in patients with type 1 diabetes mellitus (T1DM). Data Sources: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed through March 2016 using the search terms glucagon-like peptide 1 (GLP-1) agonists, incretin, liraglutide, exenatide, albiglutide, dulaglutide, type 1 diabetes mellitus. Study Selection and Data Extraction: All English-language trials that examined glycemic end points using GLP- 1 agonists in humans with T1DM were included. Data Synthesis: A total of 9 clinical trials examining the use of GLP-1 agonists in T1DM were identified. On average, hemoglobin A1C (A1C) was lower than baseline, with a maximal lowering of 0.6%. This effect was not significant when tested against a control group, with a relative decrease in A1C of 0.1% to 0.2%. In all trials examined, reported hypoglycemia was low, demonstrating no difference when compared with insulin monotherapy. Weight loss was seen in all trials, with a maximum weight loss of 6.4 kg over 24 weeks. Gastrointestinal adverse effects are potentially limiting, with a significant number of patients in trials reporting nausea. Conclusion: The use of GLP-1 agonists should be considered in T1DM patients who are overweight or obese and not at glycemic goals despite aggressive insulin therapy; however, tolerability of these agents is a potential concern. Liraglutide has the strongest evidence for use and would be the agent of choice for use in overweight or obese adult patients with uncontrolled T1DM