[PDF] Investigating The Molecular Mechanisms Regulating Dscam Alternative Splicing In Drosophila eBook

Author : Alistair Nicol Boettiger
Publisher :
Page : 376 pages
File Size : 21,57 MB
Release : 2011
Category :
ISBN :

GET BOOK

The ornate arrangement of diverse cells into specialized tissues, organs, and higher structures characteristic of multicellular organisms is all encoded from the same genome sequence. Despite their differences, morphologically distinct cells (e.g. muscle cells and neurons) must transcribe many of the same genes. Morphological indistinguishable cells must often transcribe distinct sets of genes (e.g. different odorant receptor cells). The ensemble of genes expressed in a given cell -- and the relative frequency they are expressed at, give each cell its characteristic identity more so than the presence of individual genes. Therefore understanding the genetic control of development and differentiation is a question not so much of the understanding the gene sequences themselves, but the regulatory structure of the genome which determines how they are deployed. In order for development to unravel in such a manner that each embryo makes it through the process with all the correct parts in the correct positions at the end, this process must be exceedingly precise. Though often taken for granted, this precision becomes particular impressive if one considers the frequency with which mistakes are made in intelligently designed human built assembly processes. The developing animal must position components correctly on scales of microns (e.g. tissue boundaries) and nanometers (e.g. neuron-junctions), has no external direction of assembly, and requires thermal noise to position many of its components (including essentially all transcription factors - proteins which regulate read access to the genome). It is not sufficient for the process to be precise. It must also be robust to changes in the conditions in which it operates, such as different thermal environments, nutrient conditions, and chemical environments. This robustness enables a certain degree of plasticity, such that some components of the system can change and evolve new functions, without causing catastrophic failure of the rest of the system. In my thesis research I have tried to explore some of the molecular mechanisms of gene regulation which support the precise and robust expression of multicellular genomes. Rapid advances in post-genomic technologies have exposed a broad range of fundamental differences in the organization and regulation of multicellular genomes such as Drosophila. I have worked primarily on two phenomena, the use of promoter proximal pausing as a regulatory strategy, and the use of multiple apparently redundant regulatory sequences to drive expression of the same gene. Discovery of both of these phenomena emerged from analysis of whole genome polymerase and transcription factor binding data. Using quantitative high resolution in situ and semi-automated computational image processing I have studied the detailed differences in the transcriptional activation and transcription frequency of genes regulated by these mechanisms. Through this analysis I have shown a strong correlation through more rapid and synchronous gene expression and regulation through release of promoter proximal paused polymerase. Theoretical modeling demonstrates that such an effect can be expected from regulating release of stable downstream state in a general assembly process (such as construction of the RNA Pol II pre-initiation complex). Analysis of gene expression driven by multiple enhancers with overlapping activity compared to constructs with only a single active enhancer revealed that the process by which an enhancer binds its target transcription factors and activates expression is often limiting enough that having a second independent copy can produce detectable changes in the frequency of transcription. This reduction of natural variation in gene activation is especially important under stress conditions, such as thermal stress or reduced levels of some of the activating factors. Robustness to this sort of variation may be important both for adaptation within a species and the flexibility to allow modification of interacting pathways in the course of evolutionary modification. These investigations also revealed a corrective propensity whereby the simultaneous activity of multiple enhancers, responding to repressors as well as activators, can give rise to correctly restricted gene expression even when the elements taken in isolation drive some degree of ectopic expression. So far both of these mechanisms have only been reliably documented in multicellular systems, suggesting that the precision and robustness they confer may be an innovation of metazoans in response to increased levels of coordination required to keep many cells functioning in the tight cooperation of a multicellular organism. Doubtless this is but scratching the surface of the mechanisms which ensure such precision and control. However the rapid improvements to both genomic tools and imaging technology make it like to be a promising field for further exploration for years to come.

Author : Benjamin J. Blencowe
Publisher : Springer Science & Business Media
Page : 260 pages
File Size : 18,65 MB
Release : 2008-01-23
Category : Medical
ISBN : 9780387773735

GET BOOK

Yet again Springer has reached the market before everyone. This is the first book that is solely dedicated to the topic of alternative splicing. The book contains chapters by experts in the field that cover nearly all aspects of this hugely important subject. The purpose of the text is to provide a single, authoritative source of information on alternative splicing that is accessible to researchers in diverse fields. It is suitable for beginners and experts alike.

Author : Ibrokhim Y. Abdurakhmonov
Publisher : BoD – Books on Demand
Page : 190 pages
File Size : 50,65 MB
Release : 2018-06-20
Category : Medical
ISBN : 1789232686

GET BOOK

Bioinformatics has evolved significantly in the era of post genomics and big data. Huge advancements were made toward storing, handling, mining, comparing, extracting, clustering and analysis as well as visualization of big macromolecular data using novel computational approaches, machine and deep learning methods, and web-based server tools. There are extensively ongoing world-wide efforts to build the resources for regional hosting, organized and structured access and improving the pre-existing bioinformatics tools to efficiently and meaningfully analyze day-to-day increasing big data. This book intends to provide the reader with updates and progress on genomic data analysis, data modeling and network-based system tools.

Author : Manyuan Long
Publisher : Springer Science & Business Media
Page : 198 pages
File Size : 31,44 MB
Release : 2012-12-06
Category : Science
ISBN : 9401002290

GET BOOK

Although interest in evolutionary novelties can be that these different mechanisms cooperate in the mak traced back to the time of Darwin, the appreciation ing of new genes. In the second phase of new gene evolution, conventional models of new gene evolution, and systematical experimental pursuit of the origin and evolution of new gene functions did not appear for example by gene duplication, held that the muta until the early years of last decade. Since the 1970s, tions fixed in the early stages of the new genes are Susumu Ohno, Walter Gilbert, and others from the assumed to be neutral or nearly neutral. However, it area of evolutionary genetics have made pioneer ef appears that the force of Darwinian positive selection has been detectably strong from the outset in avail forts to elaborate possibilities for major biological mechanisms, for example, gene duplication and exon able population genetic studies of young genes created through the process of exon recombination. This may shuffling, by which new gene functions could arise. However, the problem of new gene evolution did not account for a common phenomenon in phylogenetic catch significant attention among biologists generally analyses of genes with changed functions: the early even recently. One of the reasons was the lack of ex stages of such genes are usually associated with accel perimental or observational systems for investigating erated substitution rates. Nonetheless, a more general factual details of the 'birth' process of new genes.

Author : B. D. Hames
Publisher : Oxford University Press, USA
Page : 238 pages
File Size : 36,37 MB
Release : 1988
Category : Music
ISBN :

GET BOOK

This book gives a co-ordinated review of our present knowledge of eukaryotic RNA synthesis.