Exploiting Sexual Differences In Germline Biology To Resolve The Causes Of Germline Mutation
Funder
National Health and Medical Research Council
Funding Amount
$315,914.00
Summary
Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating dis ....Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating diseases, and for devising effective preventative and diagnostic measures. To attain this understanding necessitates establishing the mechanistic origins of germline mutagenesis. Two basic approaches are employed to understand this process. The first assesses the incidence of mutation in pedigrees. This identifies the spectrum of risk mutations underlying the specific disease surveyed. Because other biological processes also influence these observations, the results from this approach do not reflect the underlying germline mutation spectra and are therefore not translatable between diseases. As mutations are rare events, it is prohibitive to obtain sufficient observations to resolve the underlying mechanisms. The second approach employs comparative genomic data, and uses differences in germline biology to estimate sex-biased effects. This comparative approach benefits from the accumulation of mutations over vast periods of time. The approach has not, however, been applied to diagnose the mechanistic origins of mutations. In this project, we will apply the enormous volume of comparative sequencing data to relate components of the mutagenic spectrum with sexual differences in germline biology. The project will differentiate between different types of mutations, and their association with specific processes will be established. The results will be a determination of the relative contributions of different mechanisms of mutation to germline mutagenesis.Read moreRead less
Retracing the Early Evolution of Metazoa using Novel Methods and Strategies. Metazoa is one of the best-characterised groups of species in terms of its morphology, fossil record, development, and genetic make-up, but the phylogeny remains obscure because the fossil record is incomplete and because molecular phylogenetic methods have not yet been developed with the complexity of genomic data in mind. We will develop methods and strategies for the analysis of whole genomes, and use them in studies ....Retracing the Early Evolution of Metazoa using Novel Methods and Strategies. Metazoa is one of the best-characterised groups of species in terms of its morphology, fossil record, development, and genetic make-up, but the phylogeny remains obscure because the fossil record is incomplete and because molecular phylogenetic methods have not yet been developed with the complexity of genomic data in mind. We will develop methods and strategies for the analysis of whole genomes, and use them in studies of the mitochondrial genome. We will infer the animal phylogeny, and use it to chart the evolution of animal morphology and development, and the evolution of mitochondrial genetic codes, gene order, and nucleotide content.Read moreRead less
Adaptation to life in the dark: genomic analyses of blind beetles. This project aims to utilise a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. This project focuses on the evolution of Heat Shock protein (Hsp) genes that play critical roles in adaptation to environmental stress and the process of de-canalisation, the rel ....Adaptation to life in the dark: genomic analyses of blind beetles. This project aims to utilise a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. This project focuses on the evolution of Heat Shock protein (Hsp) genes that play critical roles in adaptation to environmental stress and the process of de-canalisation, the release of cryptic genetic variation that can allow novel morphologies to evolve in new environments. The project expects to provide further understanding of how species may potentially adapt to environmental stresses in the future, including climate change.Read moreRead less
Is regressive evolution associated with loss of gene function in subterranean animals? This project aims to investigate a fundamental biological process: the evolutionary basis for how non-functional characters, such as eyes in subterranean animals, are lost. It will use a unique model system based on eyeless water beetles, and utilise novel new genomic tools to test whether loss of characters results from gene inactivation.
Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine ....Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine how evolution works at the DNA level. This proposal will determine if animals that develop identical skull shapes, also show identical changes in their DNA. The findings will define new developmental genes and explain how selection, adaptation and evolution works at the DNA level. Read moreRead less
Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet ....Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet poorly understood issue in mitochondrial genomics and evolutionary biology. Knowledge from this project will also improve our understanding of other important issues that are associated with animal mitochondria; like the mechanisms of mitochondrial disease and ageing, and the evolution of modern humans and other animals.Read moreRead less
Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the verteb ....Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the vertebrate immune system and providing the basis for making immunological reagents which are necessary for studying monotreme diseases (as a precautionary conservation strategy).Read moreRead less
How are visual gene pathways lost and restored during reptile evolution? This project aims to investigate how complex traits are lost during evolution, and once lost if they can be regained. The project will use the diverse visual systems of snakes and lizards to shed light on the process of gene loss in degenerative lineages, and discover the mechanisms that compensate for gene losses in taxa with secondarily evolved visual capabilities- providing a case of evolutionary re-innovation in complex ....How are visual gene pathways lost and restored during reptile evolution? This project aims to investigate how complex traits are lost during evolution, and once lost if they can be regained. The project will use the diverse visual systems of snakes and lizards to shed light on the process of gene loss in degenerative lineages, and discover the mechanisms that compensate for gene losses in taxa with secondarily evolved visual capabilities- providing a case of evolutionary re-innovation in complex traits.Read moreRead less
Algebraically informed models of biological sequence evolution. To make sense of the patterns they see in the natural world, biologists across fields as diverse as genetics, epidemiology and biogeography need an accurate picture of evolutionary history. DNA sequences provide an exciting means to establish this picture of the past, but to decode it successfully requires mathematical models of how DNA evolves. Mathematical inconsistencies have been identified with current approaches. In particular ....Algebraically informed models of biological sequence evolution. To make sense of the patterns they see in the natural world, biologists across fields as diverse as genetics, epidemiology and biogeography need an accurate picture of evolutionary history. DNA sequences provide an exciting means to establish this picture of the past, but to decode it successfully requires mathematical models of how DNA evolves. Mathematical inconsistencies have been identified with current approaches. In particular, understanding the effect of natural selection in different parts of the tree of life requires models that behave robustly in the face of shifting evolutionary processes. This project aims to use insights from algebraic methods to construct mathematically consistent models of wide biological utility.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100423
Funder
Australian Research Council
Funding Amount
$369,061.00
Summary
Group theory and phylogenetics: exploiting symmetry to uncover evolutionary history. Using advanced algebra, structural symmetries inherent in phylogenetic methods will be studied and improved approaches will be derived. DNA sequences contain a wealth of information about evolutionary events that occurred millions of years ago, but extracting this information requires the application of robust methods.