Recombination confounds interpretations of Wolbachia evolution.

Wolbachia are vertically transmitted bacteria known from arthropods and nematode worms, which are maintained in host populations because they either physiologically benefit infected individuals or parasitically manipulate their reproduction. The different manipulation phenotypes are scattered across the Wolbachia phylogeny, suggesting that there have been multiple evolutions of similar phenotypes. This conclusion relies on the assumption of an absence of recombination between bacterial strains, so that the gene used to reconstruct the phylogeny reflects the evolutionary history of the genes involved in the trait. We tested for recombination by reconstructing the phylogeny of two Wolbachia genes from seven B-subdivision strains. The two genes produced mutually incompatible topologies, indicating that these lineages are subject to genetic recombination. This means that many evolutionary patterns inferred from Wolbachia phylogenies must be re-evaluated. Furthermore, recombination may be an important feature both in the evolution of the manipulation phenotypes and avoidance of Müller's ratchet. Finally, we discuss the implications of recombination for attempts to genetically engineer Wolbachia for use in the control of crop pests and human pathogens.     

L1 (LINE-1) retrotransposable elements provide a "fossil" record of the phylogenetic history of murid rodents

The single most difficult problem in phylogenetic analysis is deciding whether a shared taxonomic character is due to common ancestry or one that appeared independently due to convergence, parallelism, or reversion to an ancestral state. Mammalian L1 retrotransposons undergo periodic amplifications in which multiple copies of the elements are interspersed in the genome. Because these elements apparently are transmitted only by inheritance and are retained in the genome, a shared L1 amplification event can only be an inherited ancestral character. We propose that L1 amplification events can be an excellent tool for analyzing mammalian evolution and demonstrate here how we addressed several refractory problems in rodent systematics using L1 DNA as a taxonomic character.      

The Evolution and Genetics of Virus Host Shifts

Emerging viral diseases are often the product of a host shift, where a pathogen jumps from its original host into a novel species. Phylogenetic studies show that host shifts are a frequent event in the evolution of most pathogens, but why pathogens successfully jump between some host species but not others is only just becoming clear. The susceptibility of potential new hosts can vary enormously, with close relatives of the natural host typically being the most susceptible. Often, pathogens must adapt to successfully infect a novel host, for example by evolving to use different cell surface receptors, to escape the immune response, or to ensure they are transmitted by the new host. In viruses there are often limited molecular solutions to achieve this, and the same sequence changes are often seen each time a virus infects a particular host. These changes may come at a cost to other aspects of the pathogen''s fitness, and this may sometimes prevent host shifts from occurring. Here we examine how these evolutionary factors affect patterns of host shifts and disease emergence.     

THE DYNAMICS OF RECIPROCAL SELECTIVE SWEEPS OF HOST RESISTANCE AND A PARASITE COUNTER‐ADAPTATION IN DROSOPHILA

Host–parasite coevolution can result in consecutive selective sweeps of host resistance alleles and parasite counter‐adaptations. To illustrate the dynamics of this important but little studied form of coevolution, we have modeled an ongoing arms race between Drosophila melanogaster and the vertically transmitted sigma virus, using parameters we estimated in the field. We integrate these results with previous work showing that the spread of a resistance allele of the ref(2)P gene in the host was followed by the spread of a virus genotype, which overcomes this resistance. In line with these observations, our model predicts that there can be rapid selective sweeps in both the host and parasite, which can drive large changes in the prevalence of infection. The virus will tend to be ahead in the arms race, as incomplete dominance slows down host adaptation and selection for host resistance is weaker than selection for parasites to overcome resistance—the “life‐dinner” principle. This asymmetry in the adaptation rates results in a partial sweep of the host resistance allele, as it loses its advantage part way through the selective sweep. This well‐understood natural system illustrates how the outcome of host–parasite coevolution is determined by different population genetic parameters in the field.     

Hybridization and speciation

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.     

Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism

IntroductionEngagement of the homotypic cell-to-cell adhesion molecule cadherin-11 on rheumatoid arthritis (RA) synovial fibroblasts with a chimeric molecule containing the cadherin-11 extracellular binding domain stimulated cytokine, chemokine, and matrix metalloproteinases (MMP) release, implicating cadherin-11 signaling in RA pathogenesis. The objective of this study was to determine if cadherin-11 extracellular domain fragments are found inside the joint and if a physiologic synovial fibroblast cleavage pathway releases those fragments.MethodsCadherin-11 cleavage fragments were detected by western blot in cell media or lysates. Cleavage was interrupted using chemical inhibitors or short-interfering RNA (siRNA) gene silencing. The amount of cadherin-11 fragments in synovial fluid was measured by western blot and ELISA.ResultsSoluble cadherin-11 extracellular fragments were detected in human synovial fluid at significantly higher levels in RA samples compared to osteoarthritis (OA) samples. A cadherin-11 N-terminal extracellular binding domain fragment was shed from synovial fibroblasts after ionomycin stimulation, followed by presenilin 1 (PSN1)-dependent regulated intramembrane proteolysis of the retained membrane-bound C-terminal fragments. In addition to ionomycin-induced calcium flux, tumor necrosis factor (TNF)-α also stimulated cleavage in both two- and three-dimensional fibroblast cultures. Although cadherin-11 extracellular domains were shed by a disintegrin and metalloproteinase (ADAM) 10 in several cell types, a novel ADAM- and metalloproteinase-independent activity mediated shedding in primary human fibroblasts.ConclusionsCadherin-11 undergoes ectodomain shedding followed by regulated intramembrane proteolysis in synovial fibroblasts, triggered by a novel sheddase that generates extracelluar cadherin-11 fragments. Cadherin-11 fragments were enriched in RA synovial fluid, suggesting they may be a marker of synovial burden and may function to modify cadherin-11 interactions between synovial fibroblasts.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0647-9) contains supplementary material, which is available to authorized users.     

Fracture prevention in COPD patients; a clinical 5-step approach

Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy). Severe COPD (defined as postbronchodilator FEV₁ < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture. The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up. This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture.     

Evolution and diversity of Rickettsia bacteria

Background  

Rickettsia are intracellular symbionts of eukaryotes that are best known for infecting and causing serious diseases in humans and other mammals. All known vertebrate-associated Rickettsia are vectored by arthropods as part of their life-cycle, and many other Rickettsia are found exclusively in arthropods with no known secondary host. However, little is known about the biology of these latter strains. Here, we have identified 20 new strains of Rickettsia from arthropods, and constructed a multi-gene phylogeny of the entire genus which includes these new strains.     

Rapidly Shifting Sex Ratio across a Species Range

Sex ratios are subject to distortion by a range of inherited parasites [1]. Although it has been predicted that the presence of these elements will result in spatial and temporal variation in host sex ratio [2], [3] and [4], testing of this hypothesis has been constrained by availability of historical data. We here determine spatial and temporal variation in sex ratio in a interaction between a butterfly and male-killing Wolbachia bacteria [5] by assaying infection presence in museum specimens, and from this inferring infection prevalence and phenotype in historical populations. Comparison of contemporary and museum samples revealed profound change in four of five populations examined. Two populations become extremely female biased, associated with spread of the male-killer bacterium. One evolved from extremely female biased to a sex ratio near parity, resulting from the infection losing male-killing activity. The final population fluctuated widely in sex ratio, associated with varying frequency of the male killer. We conclude that asynchronous invasion and decline of sex-ratio distorters combines with the evolution of host suppressors to produce a rapidly changing mosaic of sex ratio. As a consequence, the reproductive ecology of the host species is likely to be fundamentally altered over short time scales [6]. Further, the study demonstrates the utility of museum specimens as “silent witnesses” of evolutionary change.