School of BioSciences - Theses
Permanent URI for this collection
Search Results
1 - 5 of 5
-
ItemA systems approach to understanding allergy, asthma and childhood wheeze( 2019)In Australia, asthma is a common respiratory disease with a significant health burden. Our current understanding of the biological mechanisms behind asthma is incomplete. It is not clear what makes a person more susceptible compared to another, nor is it clear how determinants of asthma susceptibility interact to cause disease. Childhood wheeze does not necessarily progress to asthma, and asthma itself is a heterogeneous condition that encompasses many different phenotypes, each with potentially different biology. However, we suspect that, for most affected individuals, the origins of asthma arise in early childhood, as embodied by the “hygiene hypothesis”. Events like microbial and allergen exposure in early life, as well as frequency and severity of respiratory infections, may steer the child on a course towards asthma and disease. Early prediction of disease susceptibility or severity is important because it may permit early intervention in young children, which may then limit the progression of asthma or prevent it altogether. My research thesis had three general aims: 1. To uncover hidden subgroups or “clusters” of children who share similar trajectories of immune function and susceptibility to respiratory infection; and determine how these relate to asthma and other related phenotypes. 2. To describe microbial communities in the upper respiratory tract of infants, specifically distinct patterns of change or trajectories in the microbiome that emerge as the child ages; and to determine how these relate to respiratory health, asthma, and related phenotypes. 3. To identify novel genetic determinants of asthma and related phenotypes in early childhood (including immunorespiratory clusters and microbiome trajectories), and determine how these relate to each other. Through this research, I hope to shed light on the complexity that is asthma pathogenesis. In particular, it may explain how the determinants of asthma are similar or different between individuals. With my research, it may be possible to better characterise the interlocking events that lead from disruption of normal physiology to eventual disease. Future studies can focus on the origins of asthma in specific subpopulations, as well as potential treatment targets within each subgroup. The results of this research may open up the potential for developing therapeutic and preventative measures for asthma, as well as allow earlier intervention for infants at risk of developing asthma later in life.
-
ItemClimate adaptation in Eucalyptus microcarpa (Grey Box) and implications for conservation( 2017)Restoration is an important component of conservation management, especially in highly modified landscapes. In the face of rapid environmental change, the mere presence of vegetation doesn’t necessarily equate to the long term sustainability of populations. Rather, there is a need to consider evolutionary potential in conservation planning, including restoration. This thesis investigates two key components of evolutionary potential pertinent to restoration – namely genetic diversity and climate adaptation – in an important restoration tree species in south-eastern Australia, Eucalyptus microcarpa. This thesis aims to understand how genetic diversity and local adaptation are distributed across the range of E. microcarpa and how this knowledge may help inform seed sourcing and enhance resilience of restoration plantings under climate change. To begin, I use a landscape genomic approach to explore genomic diversity in E. microcarpa and how diversity in small habitat remnants and revegetation (restored) sites compare to large remnants. This work found that small, habitat remnants and revegetation sites largely, but not completely captured patterns of genomic diversity across the landscape. Whilst overall genomic diversity was similar between site types, patterns of diversity across the genome varied between site types. These results suggest important genomic differences between site types that may influence future adaptive potential of revegetation sites and small habitat remnants. I then investigated adaptation to climate in E. microcarpa using multiple approaches. Firstly, using a landscape genomic approach, I found evidence of genomic climate adaptation in E. microcarpa. These results suggest climate adaptation to be a genome-wide phenomenon, involving many genes and genomic regions. Exploration of genomic changes that may be required to match projected climate change suggest adaptation to be via shifts in allele frequency from standing variation. In addition to suggesting a number of climate variables associated with adaptation in E. microcarpa, these results highlight the importance of genetic diversity and standing variation for maintaining adaptive potential. Utilising existing genetic resources for this species, I found evidence of heritable, genetic variation in growth and leaf traits of E. microcarpa growing in a provenance trial. Furthermore, significant trait variation between provenances and associations with climate variables suggest climate as a driver of adaptive differences. Finally, I combined the independent genomic and phenotypic analyses to provide stronger support for climate adaptation in E. microcarpa, including links between genomic variants and adaptive traits. Associations between traits and single nucleotide polymorphisms (SNPs) using putatively adaptive SNPs genotyped in provenance trial trees validated genomic results, suggesting some trait variation could be explained by these SNPs. Furthermore, links between all three sources of variation relevant to local adaptation – genotype, phenotype and climate – corroborated findings of the two independent analyses. This approach therefore provides greater support for adaptation to climate in E. microcarpa. Together these analyses address the current genetic state of restoration in E. microcarpa as well as the structure of genetic diversity and climate adaptation across its distribution. These results suggest adaptive differences within E. microcarpa that could be utilised to enhance evolutionary potential within restoration plantings.
-
ItemThe evolution of pathogenicity and isolate variation in Talaromyces marneffei( 2017)The opportunistic fungal pathogen of humans, Talaromyces marneffei, is one of very few pathogens in an order of over a thousand species and the only species that has the capacity to switch between two morphologically distinct growth forms (known as dimorphism). Growth at 25°C results in a saprophytic multicellular, hyphal form while infectious growth in a host occurs as a uninucleate unicellular yeast that resides within phagocytic cells of the immune system. The intracellular niche of T. marneffei differs significantly from the niches of other Talaromycetes. The identification of the mechanisms by which T. marneffei can survive and grow in this intracellular niche is a major aim of this study. Comparisons of the genomes of three closely related non-dimorphic, non-pathogenic species with the T. marneffei genome identified unique features that contribute to niche specific growth and the ability to cause disease. Most significant of these were an overall reduction in genome size and gene number in T. marneffei with substantial gene losses in families responsible for environmental interaction. These and other findings strongly indicate that T. marneffei has adapted to an intracellular host niche distinct from its saprophytic relatives. Against this background of gene loss three gene families were identified that had been significantly expanded in T. marneffei. These expanded gene families showed putative extracellular and cell surface localisation and consisted of cell wall galactomannoproteins (mpl family), aspartyl proteases (pop family) and a family of small proteins with very little functional characterisation in any species (mib family). Genes in the pop, mpl and mib families were over-represented in subtelomeric regions, under positive selection, had copy number variation in T. marneffei isolates and many had high levels of repetitive adjacent sequences including several transposon families. In the host T. marneffei grows as an intracellular pathogen within phagocytes and as such extracellular proteins interact directly with the host. Therefore another aim of this study was to characterise these expanded gene families and their role in pathogenesis. Deletion studies in pop genes revealed roles in yeast cell formation during intracellular growth, while high variability in cell-to-cell protein production for two mib genes suggested a role in cell surface variation when interacting with the host. Understanding the type and degree of variation within the population of a fungal pathogen can reveal its population structure and potential to adapt to stressors such as antifungal compounds. Genome wide variation in the T. marneffei population had yet to be examined therefore an aim of this study was to characterise the degree and type of this variation. To this end several clinical and environmental isolates of T. marneffei were examined for variation in chromosomal structure, which is a common means of generating phenotypic variation in other fungi. While no obvious abnormalities were observed, gene copy number variation in subtelomeric regions was widespread and several strains showed specific small mutations with impacts in antifungal resistance and phenotypic instability. Overall this study has revealed the genomic and genetic changes within T. marneffei and between it and other Talaromycetes. Many of these changes help to explain its unique niche as an intracellular pathogen within an almost entirely non-pathogenic clade. This research also highlights specific genes and gene families with roles in this pathogenesis and identifies potential therapeutic targets and genes involved in host interactions for future investigation.
-
ItemThe genomic basis of climate and host adaptation( 2017)Many species are currently threatened by the direct and indirect effects of anthropogenically driven climate change. The elevation of global temperatures and increase in variability in both temperature and precipitation pose a risk to biodiversity as species are pushed close to their thermal safety margins. Current predictions suggest a dramatic loss of species diversity and the contraction of geographical ranges of many species. Many ectothermic insects that cannot regulate their body temperature are likely to be threatened, particularly ecologically- restricted herbivorous insects that depend for on plants for food and that are often in phenological synchrony with their plant hosts. However, adaptive shifts in these species in response to host loss and climatic extremes may counter the effects of climate change to some extent. This highlights the importance of studying species-specific adaptation mechanisms including host interactions. This dissertation contributes to this overall aim by studying the genomic basis of climatic and host adaptation. I use Drosophila melanogaster as a model system at the intraspecific level, and Drosophila species from the repleta group as a model system for the comparative level. In assessing the genomic basis of host responses, I consider a much broader range of insect taxa. This dissertation begins with a study on the use of chromosome level sequencing of D. melanogaster populations from two ends of a thermal cline. I present genomic evidence for the role of the inversion 3R Payne in capturing alleles favourable to local climatic conditions in the non-inverted form, and therefore driving adaptation to climate change. The study further elucidates the impact of climatically important chromosomal inversions in driving higher linkage disequilibrium on the non-inverted form - potentially benefiting both karyotypes. In the second chapter, I develop a new pipeline, Orthonome, and tools for multi-species comparisons for prediction of orthologues and inparalogues with the highest accuracy and recall. Using Orthonome, I was able to identify a much greater level of conservation across Drosophilid lineages than earlier thought, amounting to nearly 33% better resolution than industry-accepted methods. I then use Orthonome in the third chapter to compare the genomes of 58 insect species – most of which are known to be agricultural pests. Testing across eight gene families, I present evidence for genomic patterns in only four gene families (P450s, CCEs, GSTs and ABCs) as being associated with polyphagy or particular host ranges. While three of them have been reported before, I find that ABC transporters present much stronger evidence than reflected in earlier studies, with feeding behaviour as well as host tissue displaying an effect on gene gain in more voracious pest species. Finally, in the last study, I use novel genomic data and evidence from the repleta group of drosophilids to carry out phylogenetically constrained analyses of genes potentially associated with host and thermal stress adaptation. My aim here is to find mutually exclusive evolutionary pathways to neofunctionalisation between stress tolerant cactophilic specialists and less tolerant generalists in the group. I also find a different adaptive response in the cactophilic species compared to the generalist species; these species show little lineage specific gene gain, suggesting an exception to current standing theories on neofunctionalisation for adaptation. I further discuss the applicability the species level and order level analyses for an overall detailed and systematic approach to identify the genomic basis of climatic and host adaptation.
-
ItemComparative phylogeography and diversity of Australian Monsoonal Tropics lizards( 2016)Tropical savannah biomes cover ~20% of the world’s landmass, however the biodiversity encompassed within these environments and the underlying processes that have shaped it remain poorly understood. Recent increased research to address this knowledge gap have begun to reveal surprisingly high amounts of deep, geographically-structured diversity, much of which is cryptic or hidden within morphologically similar species complexes. These patterns are especially emphasized in vertebrate taxa which are intrinsically linked to rock escarpments and ranges that dissect the savannah woodlands and grasslands of many of these biomes, hinting at a role of heterogeneous topography in structuring diversity. The remote Australian Monsoonal Tropics (AMT) spanning the north of the Australian continent is a particularly vast, and relatively undisturbed, tropical savannah region. Recent increased surveys are revealing numerous new species and endemism hotspots, indicating we are only just beginning to uncover the true biodiversity levels within this biome. Not only is there a relative paucity of knowledge regarding the present diversity within this region, but there is also limited understanding of how this diversity came to be. Phylogeographic studies can assist us in establishing current patterns of diversity and their evolutionary significance within regions and biomes. Furthermore, by comparing and contrasting the patterns and timing of diversification within and between biomes for multiple ecologically diverse taxa, we can begin to elucidate the history of these biomes and the environmental processes that have shaped the diversity we observe today. In this dissertation I aimed to better assess and establish true patterns of biodiversity and endemism within the Kimberley region of the AMT (Western Australia), and to place these patterns within a broader continental context using intra- and inter-biome comparisons in related taxa. Using geckos as a model system I took a comparative phylogeographic approach, integrating advanced next-generation genetics and morphology to establish patterns and timing of diversification across ecologically variable taxa. Within all Kimberley taxa I studied, I uncovered high levels of cryptic diversity. Much of this diversity involves especially short-range endemic lineages concentrated in key regions typically with one or more of the following factors: highly mesic conditions, island or insular environments, and unique or complex geological formations. In recognising these areas I have provided evidence of novel biodiversity hotspots and emphasised the significance of others as representing important “refugia” within the Kimberley that allow persistence and facilitate divergence of lineages through harsh periods of environmental change. These findings indicate diversification patterns are shaped by complex interactions of climatic variation, topography, and species’ ecology, allowing inference of biogeographic history and a greater ability to predict impacts of future environmental change.