Year of Publication

2011

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department

Statistics

First Advisor

Dr. Richard J. Kryscio

Abstract

Gene transcription in individual living cells is inevitably a stochastic and dynamic process. Little is known about how cells and organisms learn to balance the fidelity of transcriptional control and the stochasticity of transcription dynamics. In an effort to elucidate the contribution of environmental signals to this intricate balance, a Three State Model was recently proposed, and the transcription system was assumed to transit among three different functional states randomly.

In this work, we employ this model to demonstrate how the stochastic dynamics of gene transcription can be characterized by the three transition parameters. We compute the probability distribution of a zero transcript event and its conjugate, the distribution of the time durations in gene on or gene off periods, the transition frequency between system states, and the transcriptional bursting frequency. We also exemplify the mathematical results by the experimental data on prokaryotic and eukaryotic transcription.

The analysis reveals that no promoters will be definitely turned on to transcribe within a finite time period, no matter how strong the induction signals are applied, and how abundant the activators are available. Although stronger extrinsic signals could enhance promoter activation rate, the promoter creates an intrinsic ceiling that no signals could cross over in a finite time. Consequently, among a large population of isogenic cells, only a portion of the cells, but not the whole population, could be induced by environmental signals to express a particular gene within a finite time period. We prove that the gene on duration follows an exponential distribution, and the gene off intervals show a local maximum that is best described by assuming two sequential exponential process. The transition frequencies are determined by a system of stochastic differential equations, or equivalently, an iterative scheme of integral operators. We prove that for each positive integer n , there associates a unique time, called the peak instant, at which the nth transcript synthesis cycle since time zero proceeds most likely. These moments constitute a time series preserving the nature order of n.

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