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Title:Computational investigations of evolutionary transitions during development of the cellular translation and transcription machinery
Author(s):Roberts, Elijah
Director of Research:Luthey-Schulten, Zaida A.
Doctoral Committee Chair(s):Luthey-Schulten, Zaida A.
Doctoral Committee Member(s):Ha, Taekjip; Hwu, Wen-Mei W.; Price, Nathan D.
Department / Program:School of Molecular & Cell Bio
Discipline:Biophysics & Computnl Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
computational biology
ribosomal signatures
horizontal gene transfer
ribosomal protein S4
reaction-diffusion master equation
chemical master equation
lattice microbe
graphics processing unit (GPU)
lac operon
in vivo crowding
Abstract:Evolutionary transitions, times at which the behavior of evolution as a dynamic system dramatically changes, have occurred many times throughout the history of life on Earth. Carl Woese proposed that one such transition occurred at the root of the universal phylogenetic tree as life crossed a "Darwinian threshold". He theorized that evolution before the transition was communal, involving massive horizontal transfer of genes, whereas evolution afterward followed a more vertical path, similar to that observed today. Christian de Duve, under the term "singularities", similarly proposed a series of such transformational events in the history of life, including the development of a compartmentalized cellular nucleus. The work presented in this dissertation describes a series of computational studies designed to explore two of these transitions: the divergence of the cellular translation machinery in the three organismal lineages and the development of strategies for coping with the effects of spatial heterogeneity on gene regulation. Several new computational methodologies developed to address these questions are also presented. Ribosomal signatures, idiosyncrasies in the ribosomal RNA and/or proteins, are characteristic of the individual domains of life. Contributions from these signatures represent a significant fraction of the phylogenetic signal separating the three domains of life. The evolutionary origin of the signatures is analyzed and discussed, with the likely explanation being horizontal gene transfer within each organismal lineage following its divergence from the ancestral pool. Additional support for this hypothesis comes from a study of the phylogeny of the universal ribosomal proteins in Bacteria, where the large number of available genomes can help to decompose the complex history of these proteins. Transcription networks control the phenotype of modern cells, regulating the expression of proteins according to a genetic program. Bacteria and archaea couple transcription and translation in the cytoplasm, where the processes are subject to a great deal of spatial heterogeneity and the effects of the in vivo environment. Eukarya, on the other hand, have segregated transcription into a controlled compartment via the evolution of the nucleus. To understand the effect an evolutionary transition to complete segregation would have had, the effects of spatial heterogeneity are studied in a simple bacterial network, namely the regulatory network encoded in the lac operon. A novel method is presented for studying the effect of incorporating spatial information and molecular crowding into stochastic models of genetic circuits. By comparing to the well-stirred model, it is shown that spatial degrees of freedom and in vivo crowding can change both the noise and the mean behavior of a circuit. The spatial noise is a component of the extrinsic noise of a genetic system and bounds are placed on its contribution. Evolutionary transitions leave distinct signatures in the fabric of the cell. By studying these "molecular fossils" one can recover physical details about the transitions themselves as well as about the overall dynamics of the evolutionary process.
Issue Date:2010-05-20
Rights Information:Copyright 2010 Elijah Roberts
Date Available in IDEALS:2010-05-20
Date Deposited:May 2010

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