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GENOMIC, REGULATORY AND FUNCTIONAL DYNAMICS OF THE
DUPLICATION PROCESS
by
Kangyu Zhang
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(COMPUTATIONAL BIOLOGY AND BIOINFORMATICS)
August 2008
Copyright 2008 Kangyu Zhang
Object Description
| Title | Genomic, regulatory and functional dynamics of the duplication process |
| Author | Zhang, Kangyu |
| Author email | kangyuzhang@hotmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Computational Biology & Bioinformatics |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2008-03-20 |
| Date submitted | 2008 |
| Restricted until | Restricted until 31 July 2010. |
| Date published | 2010-07-31 |
| Advisor (committee chair) | Zhou, Xianghong Jasmine |
| Advisor (committee member) |
Li, Lei M. Marjoram, Paul |
| Abstract | Duplication is one of the most important mechanisms for evolving gene or genome complexity. Exploring how duplicated genes or genomic regions evolve has become the cornerstone of modern evolutionary theory. In Eukaryotes, over 30% of all genes are confirmed to derive directly from duplication. In the era of genomic data explosion since year two thousand, the flood of complete genome sequences from multiple species significantly facilitated its study. For example, the long debated two round hypothesis of genome duplication in the early stage of vertebrate evolution has been demonstrated via comparing several invertebrate and vertebrate genomes.; In my study I focus on the duplication process from three different aspects: DNA sequence, transcriptional regulation, and gene function. I emphasize the dynamics of the duplication process, e.g. how duplication played a role in the adaptation of the species.; At the DNA sequence level, I modeled how duplicated microsatellites evolve. When a microsatellite locus is duplicated in a diploid organism, a single pair of PCR primers may amplify as many as four distinct alleles. To study the evolution of a duplicated microsatellite, a coalescent model with symmetric stepwise mutation is considered. Conditional on the time of duplication and mutation rate, I computed the probabilities for a sampled diploid individual to amplify one, two, three, or four distinct alleles with one pair of microsatellite PCR primers. These probabilities are then studied to examine the nature of their dependence on the duplication time and the mutation rate. The results can be useful to interpret genetic variation at microsatellite loci in species with a very recent history of gene duplication.; At the transcriptional regulation level, I studied how cis-regulatory elements evolve via a comparative genomics approach. Based on the genomic sequence of 15 fungi species diverged between S.cerevisiae and S.pombe, I determined the presence or absence of ancestral pre- and post-duplication cis-regulatory binding sites, by screening the upstream sequence of the corresponding orthologous genes. This study is the first comprehensive data assessment of how cis-regulation elements evolve in duplicated genes. It demonstrates that the dominant fate of cis-regulatory elements after gene or genome duplication is the emergence of new binding sites, along with asymmetrical loss of ancestral elements in one paralog. This is contrary to previous studies arguing that the distribution of ancestral binding sites into two paralogous duplicates may be more common. My study has implications in further understanding the causality of thecomplexity in extant transcriptional regulatory network.; At the function level, I proposed a gene ontology based approach to measure functional similarity between gene products across different species. By analyzing orthologous and paralogous duplicated genes in species S.cerevisiae and S.pombe, I discovered heterogeneous rates of functional divergence across different combinations of ontologies and gene sequences. In particular, functional similarities between paralogous genes tend to be higher than in orthologous genes, suggesting convergent evolution among duplicated genes. My method can be further extended to other annotated eukaryotic species. It also has implications for all other ontology based classification systems. |
| Keyword | duplication; microsatellite; comparative genomics; regulatory elements; gene ontology; evolution |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1481 |
| Contributing entity | University of Southern California |
| Rights | Zhang, Kangyu |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-Zhang-20080731 |
| Archival file | uscthesesreloadpub_Volume29/etd-Zhang-20080731.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | GENOMIC, REGULATORY AND FUNCTIONAL DYNAMICS OF THE DUPLICATION PROCESS by Kangyu Zhang A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (COMPUTATIONAL BIOLOGY AND BIOINFORMATICS) August 2008 Copyright 2008 Kangyu Zhang |
