Multi-locus interactions and the build-up of reproductive isolation

All genes interact with other genes, and their additive effects and epistatic interactions affect an organism's phenotype and fitness. Recent theoretical and empirical work has advanced our understanding of the role of multi-locus interactions in speciation. However, relating different models to one another and to empirical observations is challenging. This review focuses on multi-locus interactions that lead to reproductive isolation (RI) through reduced hybrid fitness. We first review theoretical approaches and show how recent work incorporating a mechanistic understanding of multi-locus interactions recapitulates earlier models, but also makes novel predictions concerning the build-up of RI. These include high variance in the build-up rate of RI among taxa, the emergence of strong incompatibilities producing localized barriers to introgression, and an effect of population size on the build-up of RI. We then review recent experimental approaches to detect multi-locus interactions underlying RI using genomic data. We argue that future studies would benefit from overlapping methods like ancestry disequilibrium scans, genome scans of differentiation and analyses of hybrid gene expression. Finally, we highlight a need for further overlap between theoretical and empirical work, and approaches that predict what kind of patterns multi-locus interactions resulting in incompatibilities will leave in genome-wide polymorphism data. This article is part of the theme issue 'Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers'.Peer reviewe

Vitellogenin and vitellogenin-like gene expression patterns in relation to caste and task in the ant Formica fusca

Social insect colonies are characterized by division of labour, and extensive morphological, physiological and behavioural differences between queens and workers. The storage protein vitellogenin (Vg) affects multiple aspects of social insect life histories, and has been suggested as a key player for caste differentiation and maintenance. Recently, three genes homologous to Vg have been described in the ant Formica exsecta. Their role is currently unclear but their structural variation suggests variable functions. We examined the expression patterns of the conventional Vg and the three Vg-like genes using qRT-PCR in the common black ant Formica fusca between queens and workers, between nurse and foragers workers, and across social contexts (queenless vs. queenright nests), and sampling time. As expected, we found a significant queen caste and nurse task-related increase for the conventional Vg, while Vg-like-C displayed a consistent forager-biased expression pattern. Task (forager vs. nurse) was the only factor that explained expression variation among workers in any of the studied genes. The removal of the queen did not affect expression, although the proportion of fertile nurses increased in queenless nests. The observed expression biases suggest that in Formica fusca, the ancestral duplication has led to alternative social functions for Vg-like genes across castes and tasks. To get a broader picture of the role of gene duplications in social evolution and the roles of Vg-like genes in caste differentiation and maintenance, how these genes achieve these roles at a molecular level need to be investigated further.Peer reviewe

Cytomegalovirus sequence variability, amplicon length, and DNase-sensitive non-encapsidated genomes are obstacles to standardization and commutability of plasma viral load results

Background: Cytomegalovirus (CMV) management post-transplantation relies on quantification in blood, but inter-laboratory and inter-assay variability impairs commutability. An international multicenter study demonstrated that variability is mitigated by standardizing plasma volumes, automating DNA extraction and amplification, and calibration to the 1st-CMV-WHO-International-Standard as in the FDA-approved Roche-CAP/CTMCMV. However, Roche-CAP/CTM-CMV showed under-quantification and false-negative results in a quality assurance program (UK-NEQAS-2014). Objectives: To evaluate factors contributing to quantification variability of CMV viral load and to develop optimized CMV-UL54-QNAT. Study design: The UL54 target of the UK-NEQAS-2014 variant was sequenced and compared to 329 available CMV GenBank sequences. Four Basel-CMV-UL54-QNAT assays of 361 bp, 254 bp, 151 bp, and 95 bp amplicons were developed that only differed in reverse primer positions. The assays were validated using plasmid dilutions, UK-NEQAS-2014 sample, as well as 107 frozen and 69 prospectively collected plasma samples from transplant patients submitted for CMV QNAT, with and without DNase-digestion prior to nucleic acid extraction. Results: Eight of 43 mutations were identified as relevant in the UK-NEQAS-2014 target. All Basel-CMV-UL54 QNATs quantified the UK-NEQAS-2014 but revealed 10-fold increasing CMV loads as amplicon size decreased. The inverse correlation of amplicon size and viral loads was confirmed using 1st-WHO-International-Standard and patient samples. DNase pre-treatment reduced plasma CMV loads by > 90% indicating the presence of unprotected CMV genomic DNA. Conclusions: Sequence variability, amplicon length, and non-encapsidated genomes obstruct standardization and commutability of CMV loads needed to develop thresholds for clinical research and management. Besides regular sequence surveys, matrix and extraction standardization, we propose developing reference calibrators using 100 bp amplicons.Peer reviewe

Simultaneous BK Polyomavirus (BKPyV)-associated nephropathy and hemorrhagic cystitis after living donor kidney transplantation

BK polyomavirus (BKPyV) commonly reactivates after kidney transplantation, and can cause polyomavirus-associated nephropathy (PyVAN), whereas after allogeneic stem cell transplantation the most frequent manifestation of BKPyV is polyomavirus-associated hemorrhagic cystitis (PyVHC). Despite high-level BKPyV replication in both, the pathogenesis and manifestation of both BKPyV entities appears to differ substantially. We describe an unusual case of simultaneous PyVAN and PyVHC presenting with acute symptoms in a BKPyV-IgG positive recipient eight months after kidney transplantation from a haploidentical living donor, who was BKPyV-IgG negative. Symptoms of cystitis and viremia subsided rapidly after reduction of immunosuppression. (C) 2015 Elsevier B.V. All rights reserved.Peer reviewe

High-level JCPyV viruria after kidney transplantation-Clinical and histopathological findings

Background:The significance of JC polyomavirus (JCPyV) after kidney transplantation ranges from irrelevant to full-blown nephropathy or PML. Objectives: To investigate the clinical significance of high-level JCPyV viruria and JCPyV primary infections after kidney transplantation. Study design: JCPyV viruria was detected in routine screening by quantitative real-time PCR in 40/238 kidney transplant recipients and was high-level (> 10(7)copies/ml) in 17 patients. A protocol biopsy at the time of JCPyV viruria was available from 10 patients. Results: Peak urine viral loads were 1.0 x 10(7)-2.5 x 10(9)copies/ml in the 17 high-level viruria patients. 6/15 (40%) patients with high-level JCPyV viruria with pretransplant sera available were JCPyV IgG negative suggesting that JCPyV viruria resulted from the donor graft in most cases. No acute graft dysfunction was associated with JCPyV viruria. No positive SV40 staining was detected in protocol biopsies, and nospecific histopathology was associated with high-level viruria; JCPyV nephropathy was not found. No differences were seen in histopathology or graft function at 3 years in patients with high-level viruria compared to non-JCPyV viruric patients transplanted during the same time period, and outcome was similar in patients with presumably primary and reactivated JCPyV. The mean estimated GFR at last follow-up was 44 ml/min (range 12-60 ml/min). One graft with high-level viruria was lost 9 years posttransplant due to recurrent IgA nephropathy Conclusions: High-level JCPyV viruria seems to be associated with primary JCPyV infection reflecting the average seroprevalence of 60%, but is not stringently associated with inferior graft function or survival, or histopathological changes. c 2016 Elsevier B.V. All rights reserved.Peer reviewe

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.Peer reviewe

Recognition in Ants: Social Origin Matters

The ability of group members to discriminate against foreigners is a keystone in the evolution of sociality. In social insects, colony social structure (number of queens) is generally thought to influence abilities of resident workers to discriminate between nestmates and non-nestmates. However, whether social origin of introduced individuals has an effect on their acceptance in conspecific colonies remains poorly explored. Using egg-acceptance bioassays, we tested the influence of social origin of queen-laid eggs on their acceptance by foreign workers in the ant Formica selysi. We showed that workers from both single- and multiple-queen colonies discriminated against foreign eggs from single-queen colonies, whereas they surprisingly accepted foreign eggs from multiple-queen colonies. Chemical analyses then demonstrated that social origins of eggs and workers could be discriminated on the basis of their chemical profiles, a signal generally involved in nestmate discrimination. These findings provide the first evidence in social insects that social origins of eggs interfere with nestmate discrimination and are encoded by chemical signatures

Phenotypic plasticity of nest-mate recognition cues in formica exsecta ants

It is well established that many ant species have evolved qualitatively distinct species-specific chemical profile that are stable overlarge geographical distances. Within these species profiles quantitative variations in the chemical profile allows distinct colony-specific odours to arise (chemotypes) that are shared by all colony members. This help maintains social cohesion, includingdefence of their colonies against all intruders, including con-specifics. How these colony -level chemotypes are maintainedamong nest-mates has long been debated. The two main theories are; each ant is able to biochemically adjust its chemical profileto‘match’that of its nest-mates and or the queen, or all nest-mates share their individually generated chemical profile viatrophollaxis resulting in an average nest-mate profile. This‘mixing’idea is better known as theGestaltmodel. Unfortunately,it has been very difficult to experimentally test these two ideas in a single experimental design. However, it is now possible usingthe antFormica exsectabecause the compounds used in nest-mate recognition compounds are known. We demonstrate thatworkers adjust their profile to‘match’the dominant chemical profile within that colony, hence maintaining the colony-specificchemotype and indicates that a‘gestalt’mechanism, i.e. profile mixing, plays no or only a minor role

Genomic analysis of Sparus aurata reveals the evolutionary dynamics of sex-biased genes in a sequential hermaphrodite fish

Sexual dimorphism is a fascinating subject in evolutionary biology and mostly results from sex-biased expression of genes, which have been shown to evolve faster in gonochoristic species. We report here genome and sex-specific transcriptome sequencing of Sparus aurata, a sequential hermaphrodite fish. Evolutionary comparative analysis reveals that sex-biased genes in S. aurata are similar in number and function, but evolved following strikingly divergent patterns compared with gonochoristic species, showing overall slower rates because of stronger functional constraints. Fast evolution is observed only for highly ovary-biased genes due to female-specific patterns of selection that are related to the peculiar reproduction mode of S. aurata, first maturing as male, then as female. To our knowledge, these findings represent the first genome-wide analysis on sex-biased loci in a hermaphrodite vertebrate species, demonstrating how having two sexes in the same individual profoundly affects the fate of a large set of evolutionarily relevant genes.European Union KBBE.2013.1.2-10 European Community 311920 Fondazione Cassa di Risparmio Padova e Rovigo FCT - Foundation for Science and Technology research grant SPARCOMP under the Call ARISTEIA I of the National Strategic Reference Framework - by the EU 36 Hellenic Republic through the European Social Fundinfo:eu-repo/semantics/publishedVersio

Sources of variation in cuticular hydrocarbons in the ant formica exsecta

Phenotypic variation arises from interactions between genotype and environment, although how variation is produced and then maintained remains unclear. The discovery of the nest-mate recognition system in Formica exsecta ants has allowed phenotypic variation in chemical profiles to be quantified across a natural population of 83 colonies. We investigated if this variation was correlated or not with intrinsic (genetic relatedness), extrinsic (location, light, temperature) or social (queen number) factors. (Z)-9-Alkenes and n-alkanes showed different patterns of variance: island (location) explained only 0.2% of the variation in (Z)-9-alkenes, but 21¬–29% in n-alkanes, whereas colony of origin explained 96% and 45–49% of the variation in (Z)-9-alkenes and n-alkanes, respectively. By contrast, within-colony variance of (Z)-9-alkenes was 4%, and 23–34% in n-alkanes, supporting the function of the former as recognition cues. (Z)-9-Alkene and n-alkane profiles were correlated with the genetic distance between colonies. Only n-alkane profiles diverged with increasing spatial distance. Sampling year explained a small (5%), but significant, amount of the variation in the (Z)-9-alkenes, but there was no consistent directional trend. Polygynous colonies and populous monogynous colonies were dominated by a rich C23:1 profile. We found no associations between worker size, mound exposure, or humidity, although effect sizes for the latter two factors were considerable. The results support the conjecture that genetic factors are the most likely source of between-colony variation in cuticular hydrocarbons