File(s) under permanent embargo
Rare Codon Clusters: Enrichment, Functional Effects, Non-Random Localization and Conservation
thesis
posted on 2009-12-17, 00:00 authored by Thomas Francis ClarkeMost amino acids are encoded by more than one codon. These synonymous codons are not used with equal frequency: in every organism, some codons are used more commonly, while others are more rare. Though the encoded protein sequence is identical, selective pressures favor more common codons for enhanced translation speed and fidelity. However, rare codons persist, presumably due to neutral drift. Here, we determine whether other, unknown factors, beyond neutral drift, affect the selection and/or distribution of rare codons. We have developed a novel algorithm that evaluates the relative rareness of a nucleotide sequence used to produce a given protein sequence. We show that rare codons, rather than being randomly scattered across genes, often occur in large clusters. These clusters occur in numerous eukaryotic and prokaryotic genomes, and are not confined to unusual or rarely expressed genes; many highly expressed genes, including genes for ribosomal proteins, contain rare codon clusters. Rare codon clusters can impede ribosome translation of the rare codon sequence and are not distributed randomly throughout genes: rare codons are enriched at the 5' and 3' termini of genes from E. coli and other prokaryotes. Furthermore, rare codon clusters can be conserved across multiple homologues, indicating additional selective pressures govern the use of synonymous codons, and specifically that local pauses in translation can be beneficial for protein biogenesis.
History
Date Modified
2017-06-05Defense Date
2009-12-17Research Director(s)
Patricia L. ClarkCommittee Members
Holly Goodson Michael Ferdig Francis CastellinoDegree
- Doctor of Philosophy
Degree Level
- Doctoral Dissertation
Language
- English
Alternate Identifier
etd-12172009-210540Publisher
University of Notre DameProgram Name
- Chemistry and Biochemistry
Usage metrics
Categories
No categories selectedLicence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC