| 1. |
- Caputo, Andrea, 1988-
(författare)
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Genomic and morphological diversity of marine planktonic diatom-diazotroph associations : a continuum of integration and diversification through geological time
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Symbioses between eukaryotes and nitrogen (N2)-fixing cyanobacteria (or diazotrophs) are quite common in the plankton community. A few genera of diatoms (Bacillariophyceae) such as Rhizosolenia, Hemiaulus and Chaetoceros are well known to form symbioses with the heterocystous diazotrophic cyanobacteria Richelia intracellularis and Calothrix rhizosoleniae. The latter are also called diatom-diazotroph associations, or DDAs. Up to now, the prokaryotic partners have been morphologically and genetically characterized, and the phylogenetic reconstruction of the well conserved nifH gene (encodes for the nitrogenase enzyme) placed the symbionts in 3 clusters based on their host-specificity, i.e. het-1 (Rhizosolenia-R. intracellularis), het-2 (Hemiaulus-R. intracellularis), and het-3 (Chaetoceros-C- rhizosoleniae). Conversely, the diatom-hosts, major representative of the phytoplankton community and crucial contributors to the carbon (C) biogeochemical cycle, have been understudied.The first aim of this thesis was to genetically and morphologically characterize the diatom-hosts, and to reconstruct the evolutionary background of the partnerships and the symbiont integration in the host. The molecular-clock analysis reconstruction showed the ancient appearance of the DDAs, and the traits characterizing the ancestors. In addition, diatom-hosts bearing internal symbionts (with more eroded draft genomes) appeared earlier than diatom-hosts with external symbionts. Finally a blast survey highlighted a broader distribution of the DDAs than expected.The second aim of this thesis was to compare genetic and physiological characteristics of the DDAs symbionts with the other eukaryote-diazotroph symbiosis, i.e. prymnesiophyte-UCYN-A (or Candidatus Atelocyanobacterium thalassa). The genome comparison highlighted more genes for transporters in het-3 (external symbiont) and in the UCYN-A based symbiosis, suggesting that symbiont location might be relevant also for metabolic exchanges and interactions with the host and/or environment. Moreover, a summary of methodological biases that brought to an underestimation of the DDAs is reported.The third aim of this thesis was to determine the distribution of the DDAs in the South Pacific Ocean using a quantitative polymerase chain reaction (qPCR) approach and to outline the environmental drivers of such distribution. Among the het-groups, het-1 was the most abundant/detected and co-occurred with the other 2 symbiotic strains, all responding similarly to the influence of abiotic factors, such as temperature and salinity (positive and negative correlation, respectively). Globally, Trichodesmium dominated the qPCR detections, followed by UCYN-B. UCYN-A phylotypes (A-1, A-2) were detected without their proposed hosts, for which new oligonucleotides were designed. The latter suggested a facultative symbiosis. Finally, microscopy observations of the het-groups highlighted a discrepancy with the qPCR counts (i.e. the former were several order of magnitudes lower), leading to the idea of developing a new approach to quantify the DDAs. The fourth aim of this thesis was to develop highly specific in situ hybridization assays (CARD-FISH) to determine the presence of alternative life-stages and/or free-living partners. The new assays were applied to samples collected in the South China Sea and compared with abundance estimates from qPCR assays for the 3 symbiotic strains. Free-living cells were indeed detected along the transect, mainly at deeper depths. Free-living symbionts had two morphotypes: trichomes and single-cells. The latter were interpreted as temporary life-stages. Consistent co-occurrence of the 3 het-groups was also found in the SCS and application of a SEM model predicted positive interactions between the het groups. We interpreted the positive interaction as absence of intra-specific competition, and consistent with the previous study, temperature and salinity were predicted as major drivers of the DDAs distribution.
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| 2. |
- Tapani, Sofia, 1982
(författare)
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Stochastic modelling and analysis of early mouse development
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to model and describe dynamical events for biological cells using statistical and mathematical tools. The thesis includes five papers that all relate to stochastic modelling of cells. In order to understand the development and patterning of the early mammalian embryo, stochastic modelling has become a more important tool than ever. It allows for studying the processes that mediate the transition from pluripotency of the embryonic cells to their differentiation. It is still unclear whether the positions of cells determine their future fates. One alternative possibility is that cells are pre-specified at random positions and then sort according to a already set fate. Mouse embryonic cells are thought to be equivalent in their developmental properties until approaching the eight-cell stage. Some biological studies show, in comparison, that patterning can be present already at sperm entry and in the pronuclei migration. We investigate in Paper I the dynamics of the pronuclei migration by analysing their trajectories and find that not only do the pronuclei follow a noise corrupted path towards the centre of the egg but they also have some attraction to each other which affects their dynamics. Continuing in Paper II and III, we use these results to model this behaviour with a coupled stochastic differential equation model. This enables us to simulate distributions that describe the meeting plane between pronuclei which in turn can be related to the orientation of the first cleavage of the egg. Our results show that adding randomness in sperm entry point is different from the randomness added through the environment of the egg. We are also able to show that data sets with normal eggs and eggs treated with an actin growth inhibitor give rise to considerably different model dynamics, suggesting that the treatment is affecting the migration in an invasive way. Altering the pronuclei dynamics can alter the polarity of the egg and may transfer into the later axis-formation process. Invasiveness of experimental procedures is a difficult issue to handle. The alternative to invasive procedures is not appealing since it means that important developmental features may not be discovered because of individual variability and noise, leading to guesswork of the underlying mechanisms. The embryonic cells are easily affected by treatments performed to make the measuring, made by hand, easier or by the light exposure of the microscope. Treatments as such are used for example for producing flourescent proteins in membranes or slowing processes down. Paper IV and Paper V serve to analyse how light induced stress affects yeast cells and we employ a method for analysing the noisy non-stationary time series, which are a result of the yeast experiments, using wavelet decomposition.
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| 3. |
- Nilsson, R. Henrik, 1976
(författare)
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Fungal taxonomy and systematics in the digital era, with an outlook on the cantharelloid clade (Basidiomycota)
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fungi form a large and ubiquitous group of organisms where species identification and delimitation on morphological grounds often fall short. DNA sequences have proved an invaluable information source for these pursuits and are now routinely used in most mycological laboratories. Newl generated DNA sequences are typically compared with the entries of the large INSD sequence database for inference of taxonomic affiliations and other properties using the sequence similarity search tool BLAST. This thesis highlights some practical difficulties in using BLAST for these purposes it is for example very sensitive to the length of the sequences - and shows that improper use of BLAST appears to have had considerable repercussion on the general level of taxonomic reliability of the fungal sequences in INSD, more than 10% of which may be incorrectly identified to species level. An initiative to build a new DNA sequence database for taxonomically reliable DNA-based identification of mycorrhizal (plant-mutualistic) fungi is described. The database differs from similar initiatives in that its entries are determined to species level by pertinent experts; it allows for integrative sequence annotations, including photos and morphological descriptions; and it employs new, phylogeny-based tools for sequence identification to alleviate the concerns with simplistic, similarity-based tools as arbiters of taxonomic affiliation. That phylogenetic analyses can be beneficial also to classification and nomenclatural projects is shown in the mor enterprise, which is a weekly automaton of Agaricomycetes (mushroom-forming fungi) phylogeny. All fungal sequences from the nuclear ribosomal large subunit gene are assembled on a weekly basis; automated phylogenetic analyses are undertaken; and the resulting phylogenetic trees are displayed and analyzed for changes in clade topology and inclusiveness. The enigmatic cantharelloid clade of the Agaricomycetes is studied using a four-gene phylogenetic approach. While this heterogeneous assembly of mushroom-like, resupinate, clavarioid, and lichen-forming fungi defies any morphological attempt at indicating a close relatedness for its species, the results from the molecular analyses show that there is indeed strong evidence to support that these fungi form a monophyletic group; a restrictive circumscription of the clade to include the genera Botryobasidium, Sistotrema, Multiclavula, Membranomyces, Hydnum, Clavulina, Cantharellus, and Craterellus is advocated. Stichic basidia, and to a lesser extent parenthesome ultrastructure, are found to be characteristic of the clade, and the previously reported divergent rates of evolution for the genera Cantharellus and Craterellus are shown to be limited to the nuclear ribosomal genes. The largely resupinate, and purportedly wood-decaying, genus Sistotrema is demonstrated to hold mycorrhizal lineages, and the molecular evidence to consider the genus polyphyletic is found to be very convincing.
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| 4. |
- Ekelund Ugge, Gustaf Magnus Oskar, 1990-
(författare)
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Transcriptional biomarkers of toxicity – powerful tools or random noise? : An applied perspective from studies on bivalves
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aquatic organisms are constantly at risk of being exposed to potentially harmful chemical compounds of natural or anthropogenic origin. Biological life can for instance respond to chemical stressors by changes in gene expression, and thus, certain gene transcripts can potentially function as biomarkers, i.e. early warnings, of toxicity and chemical stress. A major challenge for biomarker application is the extrapolation of transcriptional data to potential effects at the organism level or above. Importantly, successful biomarker use also requires basal understanding of how to distinguish actual responses from background noise. The aim of this thesis is, based on response magnitude and variation, to evaluate the biomarker potential in a set of putative transcriptional biomarkers of general toxicity and chemical stress.Specifically, I addressed a selection of six transcripts involved in cytoprotection and oxidative stress: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Moreover, I used metal exposures to serve as a proxy for general chemical stress, and due to their ecological relevance and nature as sedentary filter-feeders, I used bivalves as study organisms.In a series of experiments, I tested transcriptional responses in the freshwater duck mussel, Anodonta anatina, exposed to copper or an industrial wastewater effluent, to address response robustness and sensitivity, and potential controlled (e.g. exposure concentration) and random (e.g. gravidness) sources of variation. In addition, I performed a systematic review and meta-analysis on transcriptional responses in metal exposed bivalves to (1) evaluate what responses to expect from arbitrary metal exposures, (2) assess the influence from metal concentration (expressed as toxic unit), exposure time and analyzed tissue, and (3) address potential impacts from publication bias in the scientific literature.Response magnitudes were generally small in relationship to the observed variation, both for A. anatina and bivalves in general. The expected response to an arbitrary metal exposure would generally be close to zero, based on both experimental observations and on the estimated impact from publication bias. Although many of the transcripts demonstrated concentration-response relationships, large background noise might in practice obscure the small responses even at relatively high exposures. As demonstrated in A. anatina under copper exposure, this can be the case already for single species under high resolution exposures to single pollutants. As demonstrated by the meta-regression, this problem can only be expected to increase further upon extrapolation between different species and exposure scenarios, due to increasing heterogeneity and random variation. Similar patterns can also be expected for time-dependent response variation, although the meta-regression revealed a general trend of slightly increasing response magnitude with increasing exposure times.In A. anatina, gravidness was identified as a source of random variability that can potentially affect the baseline of most assessed biomarkers, particularly when quantified in gills. Response magnitudes and variability in this species were generally similar for selected transcripts as for two biochemical biomarkers included for comparison (AChE, GST), suggesting that the transcripts might not capture early warnings more efficiently than other molecular endpoints that are more toxicologically relevant. Overall, high concentrations and long exposure durations presumably increase the likelihood of a detectable transcriptional response, but not to an extent that justifies universal application as biomarkers of general toxicity and chemical stress. Consequently, without a strictly defined and validated application, this approach on its own appears unlikely to be successful for future environmental risk assessment and monitoring. Ultimately, efficient use of transcriptional biomarkers might require additional implementation of complementary approaches offered by current molecular techniques.
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| 5. |
- Bag, Pushan, 1993-
(författare)
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How could Christmas trees remain evergreen? : photosynthetic acclimation of Scots pine and Norway spruce needles during winter
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Plants and other green organisms harvest sunlight by green chlorophyll pigments and covertit to chemical energy (sugars) and oxygen in a process called photosynthesis providing the foundation for life on Earth. Although it is unanimously believed that oceanic phytoplanktons are the main contributors to the global photosynthesis, the contribution of coniferous boreal forests distributed across vast regions of the northern hemisphere cannot be undermined. Hence boreal forests account signifificantly for social, economical and environmental sustainability. Not only do conifers thrive in the tundra regions with extreme climate, but they also maintain their needles green over the boreal winter. A question remains; what makes them so resilient? In this respect, we aimed to understand the remarkable winter adaptation strategies in two dominant boreal coniferous species,i.e., Pinus sylvestris and Picea abies. First, we mapped the transcriptional landscape in Norway spruce (Picea abies) needles over the annual cycle. Transcriptional changes in the nascent needles reflflected a sequence of developmental processes and active vegetative growth during early summer and summer. Later after maturation, transcriptome reflflected activated defense against biotic factors and acclimationin response to abiotic environmental cues such as freezing temperatures during winter. Secondly, by monitoring the photosynthetic performance of Scot pine needles, we found that the trees face extreme stress during the early spring (Feb-Mar) when sub-zero temperatures are accompanied by high solar radiation. At this time, drastic changes occur in the thylakoid membranes of the chloroplast that allows the mixing of photosystem I and photosystem II that typically remain laterally segregated. This triggers direct energy transfer from PSII to PSI and thus protects PSII from damage. Furthermore, we found that this loss of lateral segregation may be a consequence of triple phosphorylationof Lhcb1 (Light harvesting complex1 of photosystem II). The structural changes in thylakoid membranes also lead to changes inthe thylakoid macro domain organisationand pigment protein composition. Furthermore, we discovered that while PSII is protected by direct energy transfer, the protection of PSI is provided through photoreduction of oxygen by flavodiiron proteins, which in turn allows P700 to stay in an oxidised state necessary for direct energy transfer. These coordinated cascades of changes concomitantly protect both PSI and PSII to maintain the needles green over the winter.
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| 6. |
- Wieloch, Thomas, 1979-
(författare)
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Intramolecular isotope analysis reveals plant ecophysiological signals covering multiple timescales
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Our societies' wellbeing relies on stable and healthy environments. However, our current lifestyles, growth-oriented economic policies and the population explosion are leading to potentially catastrophic degradation of ecosystems and progressive disruption of food chains. Hopefully, more clarity about what the future holds in store will trigger stronger efforts to find, and adopt, problem-focused coping strategies and encourage environmentally friendly lifestyles.Forecasting environmental change/destruction is complicated (inter alia) by lack of complete understanding of plant-environment interactions, particularly those involved in slow processes such as plant acclimatisation and adaptation. This stems from deficiencies in tools to analyse such slow processes. The present work aims at developing tools that can provide retrospective ecophysiological information covering timescales from days to millennia.Natural archives, such as tree-rings, preserve plant metabolites over long timescales. Analyses of intramolecular isotope abundances in plant metabolites have the potential to provide retrospective information about metabolic processes and underlying environmental controls. Thus, my colleagues and I (hereafter we) analysed intramolecular isotope patterns in tree rings to develop analytical tools that can convey information about clearly-defined plant metabolic processes over multiple timescales. Such tools might help (inter alia) to constrain plants' capacities to sequester excess amounts of anthropogenic CO2; the so-called CO2 fertilisation effect. This, in turn, might shed light on plants' sink strength for the greenhouse gas CO2, and future plant performance and growth under climate change.In the first of three studies, reported in appended papers, we analysed intramolecular 13C/12C ratios in tree-ring glucose. In six angiosperm and six gymnosperm species we found pronounced intramolecular 13C/12C differences, exceeding 10‰. These differences are transmitted into major global C pools, such as soil organic matter. Taking intramolecular 13C/12C differences into account might improve isotopic characterisation of soil metabolic processes and soil CO2 effluxes. In addition, we analysed intramolecular 13C/12C ratios in a Pinus nigra tree-ring archive spanning the period 1961 to 1995. These data revealed new ecophysiological 13C/12C signals, which can facilitate climate reconstructions and assessments of plant-environment interactions at higher resolution; thus providing higher quality information. We proposed that 13C/12C signals at glucose C-1 to C-2 derive from carbon injection into the Calvin-Benson cycle via the oxidative pentose phosphate pathway. We concluded that intramolecular 13C/12C measurements provide valuable new information about long-term metabolic dynamics for application in biogeochemistry, plant physiology, plant breeding, and paleoclimatology.In the second study, we developed a comprehensive theory on the metabolic and ecophysiological origins of 13C/12C signals at tree-ring glucose C-5 and C-6. According to this theory and theoretical implications of the first study on signals at C-1 to C-3, analysis of such intramolecular signals can provide information about several metabolic processes. At C-3, a well-known signal reflecting CO2 uptake is preserved. The glucose-6-phosphate shunt around the Calvin-Benson cycle affects 13C/12C compositions at C-1 and C-2, while the 13C/12C signals at C-5 and C-6 reflect carbon fluxes into downstream metabolism. This theoretical framework enables further experimental studies to be conducted in a hypothesis-driven manner. In conclusion, the intramolecular approach provides information about carbon allocation in plant leaves. Thus, it gives access to long-term information on key ecophysiological processes, which could not be acquired by previous approaches.The abundance of the hydrogen isotope deuterium, δD, is important for linking the water cycle with plant ecophysiology. The main factors affecting δD in plant organic matter are commonly assumed to be the δD in source water and leaf-level evaporative enrichment. Current δD models incorporate biochemical D fractionations as constants. In the third study we showed that biochemical D fractionations respond strongly to low ambient CO2 levels and low light intensity. Thus, models of δD values in plant organic matter should incorporate biochemical fractionations as variables. In addition, we found pronounced leaf-level δD differences between α-cellulose and wax n-alkanes. We explained this by metabolite-specific contributions of distinct hydrogen sources during biosynthesis.Overall, this work advances our understanding of isotope distributions and isotope fractionations in plants. It reveals the immense potential of intramolecular isotope analyses for retrospective assessment of plant metabolism and associated environmental controls.
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| 7. |
- Sernland, Emma
(författare)
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Optimal strategies and information in foraging theory
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, I present both theoretical and empirical work where we have studied how humans and animals use information in situations where they need to continually update their information on the density of a resource. We have found that the amount of information, and the way the information is presented, are important factors for how well decisions are adapted to current circumstances. In an empirical study on humans, we found that humans seem to have a default idea of the distribution of a resource. This default idea seems to be plastic, i.e. it is adjusted according to incoming information. The way additional information was presented, as well as the information content, was important for how well the default idea was adjusted to current circumstances.By using mathematical models, we have also studied whether access to information from group members, so called public information, is one of the reasons why some species live in groups. When group members aim to maximize its intake rate of food and share both information and food items found equally, and when each individual has to pay all the cost for travelling between foraging patches, the intake rate of food will decrease with increasing group size. The animals will spend a larger proportion of the time on travelling between patches and less time on foraging the larger the group size. In this case, information sharing on food density in patches is not a reason why animals live in groups.We have also used mathematical models to study the information dynamics in a group of foraging animals that cannot both search for food and information at the same time. The animals aim to maximize their survival, and are given three behavioural choices in each time step: stay and search for food, stay and scan for information, or leave the current patch. The results show that the choice of behaviour depends on the energy reserves of the individual. An animal with low energy reserves searches for food and leaves the patch if its assessment of potential patch quality decreases to a certain level. An animal with high energy reserves chooses to stay in the patch and scan for information. In our model we assume that when one individual leaves the patch, the rest of the group also leaves. This means that it is those individuals that have low energy reserves that will make the leaving decisions for the group.In the end, we use these theories on Bayesian foraging, information updating and decision-making in order to develop a new type of effort-based quota for sustainable fisheries management: an effort-based dynamic quota (EDQ). We show that by using information from ongoing fishing combined with fishing data from earlier years, we can reach a higher maximum sustainable yield compared to using a total allowable catch (TAC).
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| 8. |
- Fallahshahroudi, Amir, 1981-
(författare)
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Domestication Effects on the Stress Response in Chickens : Genetics, Physiology, and Behaviour
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Animal domestication, the process where animals become adapted to living in proximity to humans, is associated with the alteration of multiple traits, including decreased fearfulness and stress response. With an estimated population of 50 billion, the domesticated chicken is the most populous avian species in the world. Hundreds of chicken breeds have been developed for meat and egg production, hobby or research purposes. Multidirectional selection and the relaxation of natural selection in captivity have created immense phenotypic diversity amongst domesticates in a relatively short evolutionary time. The extensive phenotypic diversity, existence of the wild ancestor, and feasibility of intercrossing various breeds makes the chicken a suitable model animal for deciphering genetic determinants of complex traits such as stress response. We used chicken domestication as a model to gain insights about the mechanisms that regulate stress response in an avian species. We studied behavioural and physiological stress response in the ancestral Red Junglefowl and one of its domesticated progenies, White Leghorn. An advanced intercross between the aforementioned breeds was later used to map genetic loci underlying modification of stress response. The general pattern of the stress response in chickens was comparable with that reported in mammals, however we identified distinctive differences in the stress modulatory pathways in chickens. We showed that changes in the expression levels of several stress modulatory genes in the brain, the pituitary and the adrenal glands underlie the observed modified stress response in domesticated chickens. Using quantitative trait loci (QTL) mapping, several QTL underlying stress induced corticosterone, aldosterone and baseline dehydroepiandrosterone (DHEA) levels were detected. As a next step, we combined QTL mapping with gene expression (eQTL) mapping and narrowed two QTL down to the putative causal genes, SERPINA10 and PDE1C. Both of these genes were differentially expressed in the adrenal glands of White Leghorn and the Red Junglefowl, had overlapping eQTL with hormonal QTL, and their expression levels in the adrenal glands were correlated with plasma levels of corticosterone and al-dosterone. These two genes thus serve as strong candidates for further functional investigation concerning modification of the stress response during domestication. This dissertation increase the knowledge about genetics and physiology of the stress response in an avian species and its modification during domestication. Our findings expand the basic knowledge about the stress response in chicken, which can potentially be used to improve welfare through appropriate genetic selection.
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| 9. |
- Görnerup, Olof, 1977
(författare)
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Inference of Hierarchical Structure in Complex Systems
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hierarchical organization is a central property of complex systems. It is even argued that a system is required to be hierarchical in order to evolve complexity within reasonable time. A hierarchy of a system is defined as the set of self-contained levels at which the system operates and can be described on. Given a dynamical system there are only specific levels that are valid. This thesis mainly concerns the definition and inference of such levels. Paper I describes an algorithm for finding hierarchical levels in stochastic processes. The method systematically explores the set of possible partitions of a process' state space and statistically determines which of the partitions that impose closed dynamics. It is applicable to moderately sized systems. In Paper II an alternative approach that applies to linear dynamical systems is presented. In this case the spectral properties of the matrix that defines a system's dynamics is utilized, which allows for analysis of large systems (with on the order of thousand states). The specification and analysis of an algorithm that is based on the results in Paper II is presented in Paper III. Paper IV applies the spectral method and a complementary agglomeration method to infer aggregated dynamics in a Markov model of codon substitutions in DNA. The standard genetic code is identified as a projection that gives the hierarchical level of amino acid substitutions. Further, higher order amino acid groups that are relatively conserved under substitutions are found to define other levels of dynamics. Paper V and VI relate hierarchical organization to primordial evolution in a conceptual model that is based on the RNA world hypothesis. A well-stirred system of processes that catalyze the production of other processes is shown to successively build higher levels of organization from simple and general-purpose components by autocatalysis.
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| 10. |
- Nandakumar, Mridula
(författare)
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Pathogen-mediated selection in the immune system of rodents : Exploring selection targets, functional effects and trade-offs
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pathogens cause disease and play an important role in shaping evolution of the host immune system. They create pressure on host immunity to evolve in numerous ways, most commonly by increasing divergence between species (positive selection) or increasing polymorphisms within a population (balancing selection). Especially with balancing selection, trade-offs between different traits, for example responses to different pathogens, are essential. Across five papers, questions related to what immune genes are under selection, how this translates to an effect on the immune response and what trade-offs occur, are addressed using rodents as study system. Paper I utilised genomes from 30 rodent species to identify signatures of positive selection in immune genes. In general, function of immune genes was a significant determinant for signs of positive selection. This effect was significant even after accounting for potential confounding factors like gene expression and protein-protein interactions. In Paper II, the focus is on a local population of bank voles in Sweden, to look for signatures of balancing selection in the complement system – a branch of innate immunity. One complement gene, FCNA, was found to be under strong balancing selection. In Paper III, FCNA polymorphism was linked to associations with natural infections of Borrelia afzelii, a common pathogen for bank voles. Papers IV and V look at how the immune response of bank voles of various genotypes differ on stimulation with B. afzelii and the human pathogen Streptococcus pyogenes, captured with transcriptome sequencing of spleen cells. In Paper IV, the analysis is focused on various genotypes of TLR2, an immune gene under balancing selection in bank voles and associated with infection prevalence of B. afzelii in the wild. A stimulation-specific effect of TLR2 on immune response was found, where the magnitude of immune response to B. afzelii, but not S. pyogenes, depends on TLR2 expression level in a TLR2 genotype-specific way. In Paper V, tradeoffs at the cis-regulatory level between the response to B. afzelii and S. pyogenes was tested by searching for polymorphisms where the alleles are expressed differently to these two stimulations. Abundant cis-regulatory variation for responses to the two bacteria was found, but there was no evidence for trade-offs. In summary, this work pushes our knowledge of what immune genes can be expected to be under pathogen-mediated selection, as heretofore understudied categories of immune function showed signs of selection. A novel basis – the combination of genotype and expression – was uncovered for functional effects of polymorphic genes. Finally, there was no evidence for trade-offs between responses to different pathogens. Investigating the nature of trade-offs in the immune system further would be necessary towards understanding the causes and consequences of pathogen-mediated selection.
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