Invasion,establishment, and range expansion of two parasitic nematodes in the Canadian Arctic

Climate warming is occurring at an unprecedented rate in the Arctic and is having profound effects on host‐parasite interactions, including range expansion. Recently, two species of protostrongylid nematodes have emerged for the first time in muskoxen and caribou on Victoria Island in the western Canadian Arctic Archipelago. Umingmakstrongylus pallikuukensis, the muskox lungworm, was detected for the first time in 2008 in muskoxen at a community hunt on the southwest corner of the island and by 2012, it was found several hundred kilometers east in commercially harvested muskoxen near the town of Ikaluktutiak. In 2010, Varestrongylus sp., a recently discovered lungworm of caribou and muskoxen was found in muskoxen near Ikaluktutiak and has been found annually in this area since then. Whereas invasion of the island by U. pallikuukensis appears to have been mediated by stochastic movement of muskoxen from the mainland to the southwest corner of the island, Varestrongylus has likely been introduced at several times and locations by the seasonal migration of caribou between the island and the mainland. A newly permissive climate, now suitable for completion of the parasite life cycles in a single summer, likely facilitated the initial establishment and now drives range expansion for both parasites.     

Mating barriers between genetically divergent strains of the parasitic nematode Haemonchus contortus suggest incipient speciation

Haemonchus contortus, in common with many nematode species, has extremely high levels of genetic variation within and between field populations derived from distant geographical locations. MHco10(CAVR), MHco3(ISE) and MHco4(WRS) are genetically divergent H. contortus strains, originally derived from Australia, Kenya and South Africa, respectively, that have been maintained by numerous rounds of in vivo experimental infection of sheep. In order to explore potential pre-zygotic competition or post-zygotic incompatibility between the strains, we have investigated the ability of MHco10(CAVR) to interbreed with either MHco3(ISE) or MHco4(WRS) during dual strain co-infections. Sheep were experimentally co-infected with 4000 infective larvae (L₃) per os of the MHco10(CAVR) strain and an equal number of either the MHco3(ISE) or the MHco4(WRS) strain L₃. The adult worm establishement rates and the proportions of F₁ progeny resulting from intra- and inter-strain mating events were determined by admixture analysis of microsatellite multi-locus genotypes. Although there was no difference in adult worm establishment rates, the proportions of F₁ progeny of both the MHco10(CAVR) × MHco3(ISE) and MHco10(CAVR) × MHco4(WRS) dual strain co-infections departed from Mendelian expectations. The proportions of inter-strain hybrid F₁ progeny were lower than the expected 50%, suggesting either pre-zygotic competition or post-zygotic incompatibility between the co-infecting strains. To investigate this further, both eggs and hatched L₁ of broods from single adult female worms recovered from each dual co-infection were genotyped. Unhatched eggs from the broods revealed no inter-strain hybrid genotype deficit, suggesting there is no pre-zygotic competition between the strains. In contrast, there was a deficit in L₁ inter-strain hybrid genotypes in the broods derived from MHco3(ISE) or MHco4(WRS) maternal parents, but not from MHco10(CAVR) maternal parents. This suggests that hybrid progeny of MHco10(CAVR) paternal parents have reduced post-zygotic development and/or viability consistent with incipient speciation of the MHco10(CAVR) strain. The presence of mating barriers between allopatric H. contortus strains has important implications for parasite ecology, including the ability of newly introduced anthelmintic-resistant parasite populations to compete and interbreed with populations already established in a region.     

Genome-wide methylation and expression differences in HPV(+) and HPV(?) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis

Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous cell carcinomas (HNSCC) have distinct risk profiles and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as a mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(−) tumors is unknown. To investigate the epigenetic regulation of gene expression in HPV-induced and carcinogen-induced cancers, we examined genome-wide DNA methylation and gene expression in HPV(+) and HPV(−) SCC cell lines. We used two platforms: the Illumina Infinium Methylation BeadArray and tiling arrays, and confirmed illustrative examples with pyrosequencing and quantitative PCR. These analyses indicate that HPV(+) cell lines have higher DNA methylation in genic and LINE-1 regions than HPV(−) cell lines. Differentially methylated loci between HPV(+) and HPV(−) cell lines significantly correlated with HPV-typed HNSCC primary tumor DNA methylation levels. Novel findings include higher promoter methylation of polycomb repressive complex 2 target genes in HPV(+) cells compared to HPV(−) cells and increased expression of DNMT3A in HPV(+) cells. Additionally, CDKN2A and KRT8 were identified as interaction hubs among genes with higher methylation and lower expression in HPV(−) cells. Conversely, RUNX2, IRS-1 and CCNA1 were major hubs with higher methylation and lower expression in HPV(+) cells. Distinct HPV(+) and HPV(−) epigenetic profiles should provide clues to novel targets for development of individualized therapeutic strategies.Key words: epigenetics, human papillomavirus, HNSCC, DNA methylation, squamous cell carcinoma, gene expression, microarrays, illumina infinium humanmethylation27 beadarray     

Fellow travellers: a concordance of colonization patterns between mice and men in the North Atlantic region

Background

In the Calvin cycle of eubacteria, the dephosphorylations of both fructose-1, 6-bisphosphate (FBP) and sedoheptulose-1, 7-bisphosphate (SBP) are catalyzed by the same bifunctional enzyme: fructose-1, 6-bisphosphatase/sedoheptulose-1, 7-bisphosphatase (F/SBPase), while in that of eukaryotic chloroplasts by two distinct enzymes: chloroplastic fructose-1, 6-bisphosphatase (FBPase) and sedoheptulose-1, 7-bisphosphatase (SBPase), respectively. It was proposed that these two eukaryotic enzymes arose from the divergence of a common ancestral eubacterial bifunctional F/SBPase of mitochondrial origin. However, no specific affinity between SBPase and eubacterial FBPase or F/SBPase can be observed in the previous phylogenetic analyses, and it is hard to explain why SBPase and/or F/SBPase are/is absent from most extant nonphotosynthetic eukaryotes according to this scenario.

Results

Domain analysis indicated that eubacterial F/SBPase of two different resources contain distinct domains: proteobacterial F/SBPases contain typical FBPase domain, while cyanobacterial F/SBPases possess FBPase_glpX domain. Therefore, like prokaryotic FBPase, eubacterial F/SBPase can also be divided into two evolutionarily distant classes (Class I and II). Phylogenetic analysis based on a much larger taxonomic sampling than previous work revealed that all eukaryotic SBPase cluster together and form a close sister group to the clade of epsilon-proteobacterial Class I FBPase which are gluconeogenesis-specific enzymes, while all eukaryotic chloroplast FBPase group together with eukaryotic cytosolic FBPase and form another distinct clade which then groups with the Class I FBPase of diverse eubacteria. Motif analysis of these enzymes also supports these phylogenetic correlations.

Conclusions

There are two evolutionarily distant classes of eubacterial bifunctional F/SBPase. Eukaryotic FBPase and SBPase do not diverge from either of them but have two independent origins: SBPase share a common ancestor with the gluconeogenesis-specific Class I FBPase of epsilon-proteobacteria (or probably originated from that of the ancestor of epsilon-proteobacteria), while FBPase arise from Class I FBPase of an unknown kind of eubacteria. During the evolution of SBPase from eubacterial Class I FBPase, the SBP-dephosphorylation activity was acquired through the transition ??from specialist to generalist??. The evolutionary substitution of the endosymbiotic-origin cyanobacterial bifunctional F/SBPase by the two light-regulated substrate-specific enzymes made the regulation of the Calvin cycle more delicate, which contributed to the evolution of eukaryotic photosynthesis and even the entire photosynthetic eukaryotes.     

A priori and a posteriori methods in comparative evolutionary studies of host–parasite associations

Brooks parsimony analysis (BPA) and reconciliation methods in studies of host–parasite associations differ fundamentally, despite using the same null hypothesis. Reconciliation methods may eliminate or modify input data to maximize fit of single parasite clades to a null hypothesis of cospeciation, by invoking different a priori assumptions, including a known host phylogeny. By examining the degree of phylogenetic congruence among multiple parasite clades, using hosts as analogs of taxa but not presuming a host phylogeny or any degree of cospeciation a priori, BPA modifies the null hypothesis of cospeciation if necessary to maintain the integrity of the input data. Two exemplars illustrate critical empirical differences between reconciliation methods and BPA: (1) reconciliation methods rather than BPA may select the incorrect general host cladogram for a set of data from different clades of parasites, (2) BPA rather than reconciliation methods provides the most parsimonious interpretation of all available data, and (3) secondary BPA, proposed in 1990, when applied to data sets in which host‐switching produces hosts with reticulate histories, provides the most parsimonious and biologically realistic interpretations of general host cladograms. The extent to which these general host cladograms, based on cospeciation among different parasite clades inhabiting the same hosts, correspond to host phylogeny can be tested, a posteriori, by comparison with a host phylogeny generated from nonparasite data. These observations lead to the conclusion that BPA and reconciliation methods are designed to implement different research programs based on different epistemologies. BPA is an a posteriori method that is designed to assess the host context of parasite speciation events, whereas reconciliation methods are a priori methods that are designed to fit parasite phylogenies to a host phylogeny. Host‐switching events are essential for explaining complex histories of host–parasite associations. BPA assumes coevolutionary complexity (historical contingency), relying on parsimony as an a posteriori explanatory tool to summarize complex results, whereas reconciliation methods, which embody formalized assumptions of maximum cospeciation, are based on a priori conceptual parsimony. Modifications of basic reconciliation methods, embodied in TreeMap 1.0 and TreeMap 2.02, represent the addition of weighting schemes in which the researcher specifies allowed departures from cospeciation a priori, with the result that TreeMap results more closely agree with BPA results than do reconciled tree analysis results.     

Onchocercosis in red deer (Cervus elaphus) from Spain.

Onchocercosis, caused by Onchocerca flexuosa, was observed in red deer (Cervus elaphus) from Spain for the first time. Adult specimens of P. flexuosa were found in nodules in subcutaneous tissues in 42 of 125 (33%) red deer between October 1994 and September 1995; intensity of infection +/- SD was 3.93 +/- 5.26 nodules per infected host. A clear seasonal pattern in the distribution of nodules was observed, with higher values of prevalence and intensity in fall and winter in contrast to spring and summer. Significant differences were found among age groups in prevalence, but not in the mean intensity. No differences in infection were apparent between male and female adult red deer.