Evolutionary Consequences of Altered Atmospheric Oxygen in Drosophila melanogaster

Twelve replicate populations of Drosophila melanogaster, all derived from a common ancestor, were independently evolved for 34+ generations in one of three treatment environments of varying PO2: hypoxia (5.0–10.1 kPa), normoxia (21.3 kPa), and hyperoxia (40.5 kPa). Several traits related to whole animal performance and metabolism were assayed at various stages via “common garden” and reciprocal transplant assays to directly compare evolved and acclimatory differences among treatments. Results clearly demonstrate the evolution of a greater tolerance to acute hypoxia in the hypoxia-evolved populations, consistent with adaptation to this environment. Greater hypoxia tolerance was associated with an increase in citrate synthase activity in fly homogenate when compared to normoxic (control) populations, suggesting an increase in mitochondrial volume density in these populations. In contrast, no direct evidence of increased performance of the hyperoxia-evolved populations was detected, although a significant decrease in the tolerance of these populations to acute hypoxia suggests a cost to adaptation to hyperoxia. Hyperoxia-evolved populations had lower productivity overall (i.e., across treatment environments) and there was no evidence that hypoxia or hyperoxia-evolved populations had greatest productivity or longevity in their respective treatment environments, suggesting that these assays failed to capture the components of fitness relevant to adaptation

Sensing and adhesion are adaptive functions in the plant pathogenic xanthomonads

<p>Abstract</p> <p>Background</p> <p>Bacterial plant pathogens belonging to the <it>Xanthomonas </it>genus are tightly adapted to their host plants and are not known to colonise other environments. The host range of each strain is usually restricted to a few host plant species. Bacterial strains responsible for the same type of symptoms on the same host range cluster in a pathovar. The phyllosphere is a highly stressful environment, but it provides a selective habitat and a source of substrates for these bacteria. Xanthomonads colonise host phylloplane before entering leaf tissues and engaging in an invasive pathogenic phase. Hence, these bacteria are likely to have evolved strategies to adapt to life in this environment. We hypothesised that determinants responsible for bacterial host adaptation are expressed starting from the establishment of chemotactic attraction and adhesion on host tissue.</p> <p>Results</p> <p>We established the distribution of 70 genes coding sensors and adhesins in a large collection of xanthomonad strains. These 173 strains belong to different pathovars of <it>Xanthomonas </it>spp and display different host ranges. Candidate genes are involved in chemotactic attraction (25 genes), chemical environment sensing (35 genes), and adhesion (10 genes). Our study revealed that candidate gene repertoires comprised core and variable gene suites that likely have distinct roles in host adaptation. Most pathovars were characterized by unique repertoires of candidate genes, highlighting a correspondence between pathovar clustering and repertoires of sensors and adhesins. To further challenge our hypothesis, we tested for molecular signatures of selection on candidate genes extracted from sequenced genomes of strains belonging to different pathovars. We found strong evidence of adaptive divergence acting on most candidate genes.</p> <p>Conclusions</p> <p>These data provide insight into the potential role played by sensors and adhesins in the adaptation of xanthomonads to their host plants. The correspondence between repertoires of sensor and adhesin genes and pathovars and the rapid evolution of sensors and adhesins shows that, for plant pathogenic xanthomonads, events leading to host specificity may occur as early as chemotactic attraction by host and adhesion to tissues.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Duffy Antigen Receptor for Chemokines Regulates Post-Fracture Inflammation

<div><p>There is now considerable experimental data to suggest that inflammatory cells collaborate in the healing of skeletal fractures. In terms of mechanisms that contribute to the recruitment of inflammatory cells to the fracture site, chemokines and their receptors have received considerable attention. Our previous findings have shown that Duffy antigen receptor for chemokines (<i>Darc</i>), the non-classical chemokine receptor that does not signal, but rather acts as a scavenger of chemokines that regulate cell migration, is a negative regulator of peak bone density in mice. Furthermore, because <i>Darc</i> is expressed by inflammatory and endothelial cells, we hypothesized that disruption of <i>Darc</i> action will affect post-fracture inflammation and consequently will affect fracture healing. To test this hypothesis, we evaluated fracture healing in mice with targeted disruption of <i>Darc</i> and corresponding wild type (WT) control mice. We found that fracture callus cartilage formation was significantly greater (33%) at 7 days post-surgery in <i>Darc</i>-KO compared to WT mice. The increased cartilage was associated with greater Collagen (<i>Col</i>) II expression at 3 days post-fracture and <i>Col</i>-X at 7 days post-fracture compared to WT mice, suggesting that <i>Darc</i> deficiency led to early fracture cartilage formation and differentiation. We then compared the expression of cytokine and chemokine genes known to be induced during inflammation. Interleukin (<i>Il</i>)-1β, <i>Il-6</i>, and monocyte chemotactic protein 1 were all down regulated in the fractures derived from <i>Darc</i>-KO mice at one day post-fracture, consistent with an altered inflammatory response. Furthermore, the number of macrophages was significantly reduced around the fractures in <i>Darc</i>-KO compared to WT mice. Based on these data, we concluded that <i>Darc</i> plays a role in modulating the early inflammatory response to bone fracture and subsequent cartilage formation. However, the early cartilage formation was not translated with an early bone formation at the fracture site in <i>Darc</i>-KO compared to WT mice.</p></div

Expression of cytokine genes at four time points post-fracture.

<p>Data are expressed as fold-change in the expression of the gene in the fractured bones compared to unfractured bones of WT mice. We analyzed 3–4 animals/mouse strain at 1 and 3 days and 5–8 mice at 7 and 15 days post-fracture.*<i>p</i><0.05 <i>vs</i> WT unfractured bones, #<i>p</i><0.05 between fractured bones of the two lines of mice.</p

Evaluation of the inflammatory cells around the fractures in <i>Darc</i>-KO and WT mice at one day post-fracture.

<p>Data are expressed as number of cells/mm² of fracture callus. We examined 5–7 animals/mouse strain. The inflammatory cells were identified by antibodies specific for CD45 (B-lymphocytes), F4/80 (macrophages) and Ly6.b.2 (neutrophils). *<i>p</i><0.05 WT vs <i>Darc</i>-KO mice.</p

Micro-CT analysis of the fracture calluses.

<p>Data are presented as the percentage of WT. Five fractures were examined from each strain of mice. BV, bone volume; TV, total volume; BV/TV, bone volume fraction.</p

Quantification of callus and cartilage development during fracture healing.

<p>Histomorphometric quantification of cartilage area (<b>A</b>) and fracture callus areas (<b>B</b>) derived from WT and <i>Darc</i>-KO mice at 7, 11 and 21 days post-fracture. We examined 5–9 animals/time point/strain of mice. *<i>p</i><0.05 WT <i>vs Darc</i>-KO mice.</p

Callus and cartilage development during fracture healing in WT and <i>Darc</i>-KO mice.

<p>Cartilage was stained with Safranin-Orange in fracture calluses derived from WT (<b>A, C, E</b>) and <i>Darc</i>-KO mice (<b>B, D, F</b>) at 7 (<b>A, B</b>), 11 (<b>C, D</b>) and 21 days post-fracture (<b>E, F</b>). Scale bar = 1 mm.</p