Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird

Acknowledgements This study was funded by a BBSRC studentship (MA Wenzel) and NERC grants NE/H00775X/1 and NE/D000602/1 (SB Piertney). The authors are grateful to Fiona Leckie, Andrew MacColl, Jesús Martínez-Padilla, François Mougeot, Steve Redpath, Pablo Vergara† and Lucy M.I. Webster for samples; Keliya Bai, Daisy Brickhill, Edward Graham, Alyson Little, Daniel Mifsud, Lizzie Molyneux and Mario Röder for fieldwork assistance; Gillian Murray-Dickson and Laura Watt for laboratory assistance; Heather Ritchie for helpful comments on manuscript drafts; and all estate owners, factors and keepers for access to field sites, most particularly Stuart Young and Derek Calder (Edinglassie), Simon Blackett, Jim Davidson and Liam Donald (Invercauld and Glas Choille), Richard Cooke and Fred Taylor† (Invermark) and T. Helps (Catterick).

Widespread range expansions shape latitudinal variation in insect thermal limits

I thank the authors of previous studies on global variation in insect thermal tolerances who have generously provided open access use of their data sets.

Arctic marine phytobenthos of northern Baffin Island

Peer reviewed

Variation in parent-offspring kinship in socially monogamous systems with extra-pair reproduction and inbreeding

Peer reviewed

Arctic marine phytobenthos of northern Baffin Island

Funded by UK Natural Environment Research Council European Commission. Grant Number: 227799 TOTAL Foundation MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) Scottish Funding Council. Grant Number: HR09011

Interpreting Human Genetic Variation through Genomics and In Vivo Models

Improvements in genomic technology, both in the increased speed and reduced cost of sequencing, have expanded the appreciation of the abundance of human genetic variation. However the sheer amount of variation, as well as the varying type and genomic content of variation, poses a challenge in understanding the clinical consequence of a single mutation. This work uses several methodologies to interpret the observed variation in the human genome, and presents novel strategies for the prediction of allele pathogenicity.

Using the zebrafish model system as an in vivo assay of allele function, we identified a novel driver of Bardet-Biedl Syndrome (BBS) in CEP76. A combination of targeted sequencing of 785 cilia-associated genes in a cohort of BBS patients and subsequent in vivo functional assays recapitulating the human phenotype gave strong evidence for the role of CEP76 mutations in the pathology of an affected family. This portion of the work demonstrated the necessity of functional testing in validating disease-associated mutations, and added to the catalogue of known BBS disease genes.

Further study into the role of copy-number variations (CNVs) in a cohort of BBS patients showed the significant contribution of CNVs to disease pathology. Using high-density array comparative genomic hybridization (aCGH) we were able to identify pathogenic CNVs as small as several hundred bp. Dissection of constituent gene and in vivo experiments investigating epistatic interactions between affected genes allowed for an appreciation of several paradigms by which CNVs can contribute to disease. This study revealed that the contribution of CNVs to disease in BBS patients is much higher than previously expected, and demonstrated the necessity of consideration of CNV contribution in future (and retrospective) investigations of human genetic disease.

Finally, we used a combination of comparative genomics and in vivo complementation assays to identify second-site compensatory modification of pathogenic alleles. These pathogenic alleles, which are found compensated in other species (termed compensated pathogenic deviations [CPDs]), represent a significant fraction (from 3 – 10%) of human disease-associated alleles. In silico pathogenicity prediction algorithms, a valuable method of allele prioritization, often misrepresent these alleles as benign, leading to omission of possibly informative variants in studies of human genetic disease. We created a mathematical model that was able to predict CPDs and putative compensatory sites, and functionally showed in vivo that second-site mutation can mitigate the pathogenicity of disease alleles. Additionally, we made publically available an in silico module for the prediction of CPDs and modifier sites.

These studies have advanced the ability to interpret the pathogenicity of multiple types of human variation, as well as made available tools for others to do so as well.

Dynamique de la variation génétique et épigénétique chez un vertébré kleptogène

La variation phénotypique est essentielle à la persistance des organismes dans le temps ainsi qu’à la colonisation de nouveaux habitats. Les principales sources de variation phénotypique sont la génétique et l'épigénétique. L'épigénétique a été proposé comme un atout important pour les organismes asexués pour compenser le manque de diversité génétique. L'objectif de cette étude est d'évaluer si l’absence de variation génétique est compensée par l'épigénétique en comparant les profils de méthylation d’individus gynogènes et kleptogènes des hybrides de salamandre à points bleus. Les individus échantillonnés s’organisent en cinq groupes génétiquement différenciés, provenant du même haplome paternel A. jeffersonianum. Deux des cinq groupes sont exclusivement gynogènes, pour des raisons écologiques ou génomiques. Les trois autres groupes sont formés d’individus parfois kleptogènes, car ils présentent une variation génétique plus élevée au sein d’un site qu’entre les sites, en plus de porter des allèles très divergents par rapport à la distribution globale des allèles hybrides, trouvés en haute fréquence dans les populations sympatriques de A. laterale. Les patrons épigénétiques sont variables et distincts entre les cinq groupes génétiques. Les groupes gynogènes sont les seuls à présenter un effet environnemental significatif sur leurs patrons épigénétiques, suggérant que ces individus clonaux doivent être en mesure de maximiser leur potentiel de variation épigénétique pour faire face à des variations environnementales.

Results from a stable isotope tracer experiment in Potter Cove, King George Island, Antarctica

Antarctic meiofauna is still strongly understud- ied, and so is its trophic position in the food web. Primary producers, such as phytoplankton, and bacteria may repre- sent important food sources for shallow water metazoans, and the role of meiobenthos in the benthic-pelagic coupling represents an important brick for food web understanding. In a laboratory, feeding experiment 13C-labeled freeze- dried diatoms (Thalassiosira weissflogii) and bacteria were added to retrieved cores from Potter Cove (15-m depth, November 2007) in order to investigate the uptake of 3 main meiofauna taxa: nematodes, copepods and cumaceans. In the surface sediment layers, nematodes showed no real difference in uptake of both food sources. This outcome was supported by the natural delta 13C values and the community genus composition. In the first centimeter layer, the dominant genus was Daptonema which is known to be opportunistic, feeding on both bacteria and diatoms. Copepods and cumaceans on the other hand appeared to feed more on diatoms than on bacteria. This may point at a better adaptation to input of primary production from the water column. On the other hand, the overall carbon uptake of the given food sources was quite low for all taxa, indicating that likely other food sources might be of relevance for these meiobenthic organisms. Further studies are needed in order to better quantify the carbon requirements of these organisms.

Seawater carbonate chemistry during a Ishigaki Island (Japan) coral reef seasonal observations, 2005

Monitoring seawater CO2 for a full year with seasonal observations of community metabolism in Ishigaki Island, Japan, revealed seasonal variation and anomalous values owing to the bleaching event in 1998. The daily average pCO2 showed a seasonal pattern on an annual scale, 280 to 320 ?atm in winter and 360 to 400 ?atm in summer, which was determined primarily by the seasonal change in seawater temperature. By contrast, the range in the diel variation in pCO2, 400 to 500 ?atm in summer 200 to 300 ?atm in winter, was attributed to the seasonal variation in community metabolism: Gross primary production (P g ) and respiration (R) were high in summer and low in winter. During the 1998 bleaching event, although P g and R increased, community excess organic production (E) decreased by three quarters compared with the same month in 1999, when the coral community showed high recovery. This change in metabolism led to large diel range and increased average value of pCO2 levels in the seawater on the reef flat. The decrease in the range and increase in the average value of pCO2 were observed by monitoring the Palau barrier reef flat, where overall mortality of corals occurred after the bleaching. All the metabolic parameters, P g , R, E and calcification (G) were reduced by half after the bleaching, which increased the average pCO2 value by 10 ?atm and decreased its diel range from 200-400 ?atm to 100-200 ?atm. Bleaching and resultant mortality of coral reefs led to degradation of their metabolic performance, and thus resulted in the loss of their active interaction with the carbon cycle.

(Table 1) Methane concentrations, MOX rates and MOB abundance in arctic aquatic ecosystems of the Lena Delta, Northeast Siberia

Large amounts of organic carbon are stored in Arctic permafrost environments, and microbial activity can potentially mineralize this carbon into methane, a potent greenhouse gas. In this study, we assessed the methane budget, the bacterial methane oxidation (MOX) and the underlying environmental controls of arctic lake systems, which represent substantial sources of methane. Five lake systems located on Samoylov Island (Lena Delta, Siberia) and the connected river sites were analyzed using radiotracers to estimate the MOX rates, and molecular biology methods to characterize the abundance and the community composition of methane-oxidizing bacteria (MOB). In contrast to the river, the lake systems had high variation in the methane concentrations, the abundance and composition of the MOB communities, and consequently, the MOX rates. The highest methane concentrations and the highest MOX rates were detected in the lake outlets and in a lake complex in a floodplain area. Though, in all aquatic systems we detected both, Type I and II MOB, in lake systems we observed a higher diversity including MOB, typical of the soil environments. The inoculation of soil MOB into the aquatic systems, resulting from permafrost thawing, might be an additional factor controlling the MOB community composition and potentially methanotrophic capacity.

Mega-epibenthos at Bouvet Island (South Atlantic)

Mega-epibenthic diversity was analysed using a seabed photography at four stations off Bouvet Island and one station at the Spiess Seamount in the South Atlantic. Surprisingly, the intermediate-scale diversity within the area of investigation was not lower compared to that on the Patagonian shelf and only moderately lower than that on the Antarctic continental shelf. This result is incompatible with Mac Arthur and Wilson's Island Biogeography Theory describing species richness as a function of immigration of new species into an area and its extension. The relatively high species number and the very small extension of the Bouvet shelf compared to the much larger continental shelves of the other two areas can be explained by long-range dispersal of marine benthic animals in the Antarctic Circumpolar Current and high habitat heterogeneity. The observed uncoupling of intermediate-scale from large-scale background species diversity on the Antarctic shelf raises the question whether in these benthic systems an upper capacity limit for diversity exists.

Seawater carbonate chemistry, virioplankton and bacterioplankton in a shallow CO2-dominated hydrothermal vent (Panarea Island, Tyrrhenian Sea)

Gas hydrothermal vents are used as a natural analogue for studying the effects of CO2 leakage from hypothetical shallow marine storage sites on benthic and pelagic systems. This study investigated the interrelationships between planktonic prokaryotes and viruses in the Panarea Islands hydrothermal system (southern Tyrrhenian Sea, Italy), especially their abundance, distribution and diversity. No difference in prokaryotic abundance was shown between high-CO2 and control sites. The community structure displayed differences between fumarolic field and the control, and between surface and bottom waters, the latter likely due to the presence of different water masses. Bacterial assemblages were qualitatively dominated by chemo- and photoautotrophic organisms, able to utilise both CO2 and H2S for their metabolic requirements. From significantly lower virioplankton abundance in the proximity of the exhalative area together with particularly low Virus-to-Prokaryotes Ratio, we inferred a reduced impact on prokaryotic abundance and proliferation. Even if the fate of viruses in this particular condition remains still unknown, we consider that lower viral abundance could reflect in enhancing the energy flow to higher trophic levels, thus largely influencing the overall functioning of the system.

Accommodating Muslim Minorities in Secular Societies: Public Education in England, Scotland, Ontario, and Quebec

Abstract This thesis examines one of the most sensitive challenges facing contemporary democracies: the accommodation of Muslim minorities in public institutions and services. It focuses on the field of education, and on two particular issues: the public funding of Islamic schools and the accommodation of Muslim needs in public secular schools. The analysis is based on an examination of outcomes in four jurisdictions that differ significantly in the level of accommodation that has emerged: England, Scotland, Ontario, and Quebec. I seek to explain why such variation in outcomes exists among these four cases. I draw on four bodies of literature to underpin the theoretical framework: historical institutionalism, political mobilization by civil society, political parties, and ideationalism. My argument can be summarized simply; historic church-state settlements, unique in each case, are the most important factor explaining the variation in outcomes in England, Scotland, Ontario, and Quebec. In some cases, the historic church-state template is incrementally adapted to accommodate Muslim minorities. In other cases, relatively little accommodation occurs and the path-dependent trajectory of church-state relations remains entrenched. While the historic church-state template is a necessary factor in the explanation, it does not fully account for the variation. For a more complete picture, I demonstrate that there are several additional key factors that also shape the outcomes: first, national identity and public attitudes towards immigration and immigrants; second, the extent of mobilization by political agents, such as civil society organizations and historic churches; and third, the response of political parties to demands by Muslims for institutional accommodation. Ultimately, I conclude that Muslims in these jurisdictions are receiving some accommodation, but the process is slow and partial. This thesis makes important theoretical and empirical contributions to the discussion of Muslim integration in liberal democratic states. First, a framework has yet to be developed that considers the theoretical implications of institutional accommodation of Muslims; I address this gap. Second, this research demonstrates the utility of historical institutionalism in explaining the adaptation of church-state templates to accommodate Muslims’ demands. Last, this study makes an original contribution by comparing the cases of England, Scotland, Ontario, and Quebec in the accommodation of Muslims in education. A comparison of Canada with the United Kingdom has not yet been done.  

Changes in the Ecology and Abundance of Smallmouth Bass in Lake Ontario: 1958-2014

Understanding the reasons for long-term population change in a species requires an evaluation of ecological variables that may account for the observed dynamics. In this study, long-term changes in indices of Smallmouth Bass condition and population levels were examined for eastern Lake Ontario and the Bay of Quinte. Smallmouth Bass are an extremely important recreational fish species native to Lake Ontario. They have experienced numerous changes in their environment through direct human impacts, climate change, predation, and habitat sharing with non-native species. Smallmouth Bass have experienced an increase in body length and weight likely due to a diet shift from crayfish to predominantly Round Gobies which has allowed them to increase their growth rate. According to existing assessment data however, this increase in body size has not been associated with an increase in abundance. Long-term data from gill net sampling shows that Smallmouth Bass populations have been declining since the late 1980s with no indication of recovery. This could be due to a variety of factors, but it is most likely due to a change in the selectivity of gill nets because of the change in body size as well as a habitat shift away from gill net sampling sites. Adjusting for gill net selectivity has revealed that sub-adult bass abundance is currently greater than it was historically, and that very large bass are likely not being retained within the gill nets that are currently used. The use of a long-term data set in this study has led to a much better understanding of Smallmouth Bass abundance and ecology.