76 research outputs found
Directed Mutations Recode Mitochondrial Genes: From Regular to Stopless Genetic Codes
Mitochondrial genetic codes evolve as side effects of stop codon ambiguity: suppressor tRNAs with anticodons translating stops transform genetic codes to stopless genetic codes. This produces peptides from frames other than regular ORFs, potentially increasing protein numbers coded by single sequences. Previous descriptions of marine turtle Olive Ridley mitogenomes imply directed stop-depletion of noncoding +1 gene frames, stop-creation recodes regular ORFs to stopless genetic codes. In this analysis, directed stop codon depletion in usually noncoding gene frames of the spiraling whitefly Aleurodicus dispersusʼ mitogenome produces new ORFs, introduces stops in regular ORFs, and apparently increases coding redundancy between different gene frames. Directed stop codon mutations switch between peptides coded by regular and stopless genetic codes. This process seems opposite to directed stop creation in HIV ORFs within genomes of immunized elite HIV controllers. Unknown DNA replication/edition mechanisms probably direct stop creation/depletion beyond natural selection on stops. Switches between genetic codes regulate translation of different gene frames
28th Fungal Genetics Conference
Full abstracts from the 28th Fungal Genetics Conference Asilomar, March 17-22, 2015
Genes: Multigene Families, Control of Gene Expression, Genetic contributions to Human Diseases, including Chromosomal Fragile Sites and ‘Dynamic’ and ‘Non-self’ Mutations
The early work in this thesis utilizes the general approach of comparative analysis. In order to find out the relationship between entities (either functional or genetic) my colleagues and I have attempted to identify the important elements by detecting similarity between those entities that act in a similar manner. The philosophy behind this approach is simply that when two distinct objects perform a similar process then the requirements essential for that process will be revealed as similarities between those objects above a noise of difference between them. The use of comparative analysis in biological systems is an attempt to identify natural order from apparent chaos. This work includes but is not limited to :- 1. discovery of the family of kallikrein genes and exploration of their roles in biology, 2. identification of the DNA sequence elements required for hormonal and heavy metal control of metallothionein gene expression 3. discovery of at least some of the necessary and sufficient conditions for the appearance of fragile sites on chromosomes, and their consequent contributions to disease, 4. the molecular properties of repeat DNA sequence expansion that lead to dynamic mutation and consequent fragile site expression and / or disease pathogenesis. In a sense the use of genetic animal models in order to study gene function and pathogenesis follows similar logic of comparative analysis – the mutation of a single endogenous gene or the expression of a single introduced mutated gene in a (presumed) constant genetic background to enable the biological consequences of the genetic mutation or aberrant gene expression by comparing animals from the ‘wild-type’ or parent line with those that now carry the mutation or altered gene. This approach has been utilized in the most recent work contained herein as a means to determine gene function and / or to model human genetic disease pathogenesis, specifically pathogenic mechanisms of the protein WWOX in cancer and expanded repeat RNAs in neurodegenerative diseases. The culmination of this recent work is the development of an hypothesis – 4. that expanded repeat double-stranded RNA leads to neurodegeneration through its recognition by the RNA-binding pattern recognition receptors as a ‘non-self’ or foreign nucleic acid due to a paucity of RNA modification. The resultant pathogenic mechanism is therefore autoinflammatory disease. Given the wide range and variety of evidence of inflammatory activation in neurodegenerative diseases in general, this mechanism is therefore hypothesized to be the general causal mechanism for most (or all) of these diseases. A specific Introduction - highlighting the nature and significance of the work, and a Conclusion – of how this work has contributed to knowledge, are given at the start of each chapter, while the impact of the various components of this work is indicated by the number of citations for each of the included publications. Authorship contributions to each of the included publications in this work are also indicated with each specific reference.Thesis (DSc) -- University of Adelaide, School of Biological Sciences, 202
Annotated Cell and Molecular Biology 5e: What We Know and How We Found Out
https://dc.uwm.edu/biosci_facbooks_bergtrom/1013/thumbnail.jp
Basic Cell and Molecular Biology 5e: What We Know and How We Find Out
https://dc.uwm.edu/biosci_facbooks_bergtrom/1014/thumbnail.jp
RNA, the Epicenter of Genetic Information
The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information. Key Features Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other. Integrates the influences of biochemistry and genetics on the landscape of molecular biology. Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress. Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA. Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology. Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers
Recommended from our members
Probabilistic Reconstruction and Comparative Systems Biology of Microbial Metabolism
With the number of sequenced microbial species soon to be in the tens of thousands, we are in a unique position to investigate microbial function, ecology, and evolution on a large scale. In this dissertation I first describe the use of hundreds of in silico models of bacterial metabolic networks to study the long-term the evolution of growth and gene-essentiality phenotypes.
The results show that, over billions of years of evolution, the conservation of bacterial phenotypic properties drops by a similar fraction per unit time following an exponential decay. The analysis provides a framework to generate and test hypotheses related to the phenotypic evolution of different microbial groups and for comparative analyses based on phenotypic properties of species. Mapping of genome sequences to phenotypic predictions -such as used in the analysis just described- critically relies on accurate functional annotations.
In this context, I next describe GLOBUS, a probabilistic method for genome-wide biochemical annotations. GLOBUS uses Gibbs sampling to calculate probabilities for each possible assignment of genes to metabolic functions based on sequence information and both local and global genomic context data. Several important functional predictions made by GLOBUS were experimentally validated in Bacillus subtilis and hundreds more were obtained across other species. Complementary to the automated annotation method, I also describe the manual reconstruction and constraints-based analysis of the metabolic network of the malaria parasite Plasmodium falciparum. After careful reconciliation of the model with available biochemical and phenotypic data, the high-quality reconstruction allowed the prediction and in vivo validation of a novel potential antimalarial target. The model was also used to contextualize different types of genome-scale data such as gene expression and metabolomics measurements.
Finally, I present two projects related to population genetics aspects of sequence and genome evolution. The first project addresses the question of why highly expressed proteins evolve slowly, showing that, at least for Escherichia coli, this is more likely to be a consequence of selection for translational efficiency than selection to avoid misfolded protein toxicity. The second project investigates genetic robustness mediated by gene duplicates in the context of large natural microbial populations. The analysis shows that, under these conditions, the ability of duplicated yeast genes to effectively compensate for the loss of their paralogs is not a monotonic function of their sequence divergence
- …