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

Hybridization between species can either promote or impede adaptation. But there is a deficit in our understanding of the genetic basis of hybrid fitness, especially in non-domesticated organisms, and when populations are facing environmental stress. We made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species. We exposed populations to ten toxins and sequenced the most resilient hybrids on low coverage using ddRADseq to investigate four aspects of their genomes: 1) hybridity, 2) interspecific heterozygosity, 3) epistasis (positive or negative associations between non-homologous chromosomes) and 4) ploidy. We used linear mixed effect models and simulations to measure to which extent hybrid genome composition was contingent on the environment. Genomes grown in different environments varied in every aspect of hybridness measured, revealing strong genotype-environment interactions. We also found selection against heterozygosity or directional selection for one of the parental alleles, with larger fitness of genomes carrying more homozygous allelic combinations in an otherwise hybrid genomic background. In addition, individual chromosomes and chromosomal interactions showed significant species biases and pervasive aneuploidies. Against our expectations, we observed multiple beneficial, opposite-species chromosome associations, confirmed by epistasis- and selection-free computer simulations, which is surprising given the large divergence of parental genomes (∼15%). Together, these results suggest that successful, stress-resilient hybrid genomes can be assembled from the best features of both parents without paying high costs of negative epistasis. This illustrates the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of genetically diverse hybrid populations

Effects of interspecific gene flow on the phenotypic variance–covariance matrix in Lake Victoria Cichlids

Quantitative genetics theory predicts adaptive evolution to be constrained along evolutionary lines of least resistance. In theory, hybridization and subsequent interspecific gene flow may, however, rapidly change the evolutionary constraints of a population and eventually change its evolutionary potential, but empirical evidence is still scarce. Using closely related species pairs of Lake Victoria cichlids sampled from four different islands with different levels of interspecific gene flow, we tested for potential effects of introgressive hybridization on phenotypic evolution in wild populations. We found that these effects differed among our study species. Constraints measured as the eccentricity of phenotypic variance–covariance matrices declined significantly with increasing gene flow in the less abundant species for matrices that have a diverged line of least resistance. In contrast, we find no such decline for the more abundant species. Overall our results suggest that hybridization can change the underlying phenotypic variance–covariance matrix, potentially increasing the adaptive potential of such populations

Interspecific Hybridization Increased in Congeneric Flatfishes after the Prestige Oil Spill

Marine species with relatively low migratory capacity are threatened by habitat alterations derived from human activities. In November 2002 the tanker Prestige sank off the Spanish northwest coast releasing 70,000 tons of fuel and damaging biota in the area. Despite efforts to clean the damaged areas, fuel remnants have affected marine species over the last nine years. This study is focused on two flatfish, Lepidorhombus boscii (four-spotted megrim) and L. whiffiagonis (megrim), whose spawning areas are located at the edge of the continental platform. We have analyzed megrim samples from North Spanish and French waters obtained before and after the oil spill. Genotypes at the nuclear marker 5S rDNA indicate a significant increase in interspecific hybridization after the Prestige accident, likely due to forced spawning overlap. The mitochondrial D-Loop region was employed for determining the direction of hybrid crosses, which were most frequently L. boscii female x L. whiffiagonis male. Reduced ability of L. boscii females to select conspecific mates would explain such asymmetric hybridization. To our knowledge this is the first time that increased hybridization between fish species can be associated to an oil spill. These results illustrate the potential long-term effect of petrol wastes on wild fish species

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

Reproducibility of $\textit{in vivo}$ research using the mouse as a model organism depends on many factors, including experimental design, strain or stock, experimental protocols, and methods of data evaluation. Gross and histopathology are often the endpoints of such research and there is increasing concern about the accuracy and reproducibility of diagnoses in the literature. To reproduce histopathological results, the pathology protocol, including necropsy methods and slide preparation, should be followed by interpretation of the slides by a pathologist familiar with reading mouse slides and familiar with the consensus medical nomenclature used in mouse pathology. Likewise, it is important that pathologists are consulted as reviewers of manuscripts where histopathology is a key part of the investigation. The absence of pathology expertise in planning, executing and reviewing $\textit{in vivo}$ research using mice leads to questionable pathology-based findings and conclusions from studies, even in high-impact journals. We discuss the various aspects of this problem, give some examples from the literature and suggest solutions.This work was supported in part by US National Institutes of Health grants R01 AR049288, CA089713 and R21 AR063781 (to J.P.S.) and by The Warden and Fellows of Robinson College, Cambridge (to P.N.S.)

Hybrid speciation in Heliconius butterflies? A review and critique of the evidence

The evidence supporting the recent hypothesis of a homoploid hybrid origin for the butterfly species Heliconius heurippa is evaluated. Data from selective breeding experiments, mate-choice studies, and a wide variety of DNA markers are reviewed, and an alternative hypothesis for the origin of the species and its close relatives is proposed. A scenario of occasional red wing-pattern mutations in peripheral populations of Heliconius cydno with subsequent adaptive convergence towards sympatric mimicry rings involving H. melpomene and H. erato is offered as an alternative to the HHS hypothesis. Recent twists of this tale are addressed in a postscript

Diagnostic, prognostic and predictive value of cell-free miRNAs in prostate cancer : A systematic review

Publisher Copyright: © 2016 Endzeliņš et al.Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolent disease. Treatment outcome and management of prostate cancer could be improved by the development of non-invasive biomarker assays that aid in increasing the sensitivity and specificity of prostate cancer screening, help to distinguish aggressive from indolent disease and guide therapeutic decisions. Prostate cancer cells release miRNAs into the bloodstream, where they exist incorporated into ribonucleoprotein complexes or extracellular vesicles. Later, cell-free miRNAs have been found in various other biofluids. The initial RNA sequencing studies suggested that most of the circulating cell-free miRNAs in healthy individuals are derived from blood cells, while specific disease-associated miRNA signatures may appear in the circulation of patients affected with various diseases, including cancer. This raised a hope that cell-free miRNAs may serve as non-invasive biomarkers for prostate cancer. Indeed, a number of cell-free miRNAs that potentially may serve as diagnostic, prognostic or predictive biomarkers have been discovered in blood or other biofluids of prostate cancer patients and need to be validated in appropriately designed longitudinal studies and clinical trials. In this review, we systematically summarise studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, we discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies.publishersversionPeer reviewe

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe