The Effect of Synonymous Codon Usage on Nucleosome Positioning

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The Effect of Synonymous Codon Usage on Nucleosome Positioning

Type: Master thesis
Title: The Effect of Synonymous Codon Usage on Nucleosome Positioning
Author: Bird, Rhys
Issue Date: 2017-07
Keywords: Nucleosome positioning, codon usage, DNA, biophysics
Abstract: Nucleosomes can influence gene regulation by acting as repressors when located on top of genes. Because of this, nucleosome positioning has been the subject of many studies. One of the determinants of nucleosome positioning is the DNA sequence itself as the mechanical properties of a sequence determine its binding affinity. A recent study showed that it is theoretically possible to change coding sequences to increase binding affinity thereby affecting nucleosome positioning. This can be seen as the multiplexing of genetic and mechanical information. By using a probabilistic model, we now investigate if gene sequences can be altered synonymously to place a nucleosome with base pair precision. By exchanging synonymous codons through a modified Monte Carlo simulation, the mechanical properties of the DNA are altered while keeping the genetic code intact. We find that for 93.7\% of the nucleosome positions on S. cerevisiae genes a minimum of the nucleosome energy landscape can be reached, allowing for the placement of a nucleosome. Additionally, we examined synonymous codon usage in regions of high nucleosome occupancy in the C. elegans genome. It appears that the choice in codon is biased mostly favouring codons with a higher GC content (as this correlates with nucleosome occupancy), but not exclusively. This might be an indication of a selective pressure to synonymously alter DNA in order to facilitate nucleosome binding.
Supervisor: Schiessel, Helmut
Faculty: Faculty of Science
Department: Physics (Master)
Specialisation: Theoretical Physics
ECTS Credits: 8

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