The genetic code gives precise instructions on how to translate codons into amino acids. Due to the degeneracy of the genetic code & mdash;18 out of 20 amino acids are encoded for by more than... Show moreThe genetic code gives precise instructions on how to translate codons into amino acids. Due to the degeneracy of the genetic code & mdash;18 out of 20 amino acids are encoded for by more than one codon & mdash;more information can be stored in a basepair sequence. Indeed, various types of additional information have been discussed in the literature, e.g., the positioning of nucleosomes along eukaryotic genomes and the modulation of the translating efficiency in ribosomes to influence cotranslational protein folding. The purpose of this study is to show that it is indeed possible to carry more than one additional layer of information on top of a gene. In particular, we show how much translation efficiency and nucleosome positioning can be adjusted simultaneously without changing the encoded protein. We achieve this by mapping genes on weighted graphs that contain all synonymous genes, and then finding shortest paths through these graphs. This enables us, for example, to readjust the disrupted translational efficiency profile after a gene has been introduced from one organism (e.g., human) into another (e.g., yeast) without greatly changing the nucleosome landscape intrinsically encoded by the DNA molecule. Show less
DNA carries various forms of information. Out of these forms of information the most well-known is classical genetic information. Throughout this dissertation we discuss what is often referred to... Show moreDNA carries various forms of information. Out of these forms of information the most well-known is classical genetic information. Throughout this dissertation we discuss what is often referred to as the second layer of information on DNA: DNA mechanics. A sequence consisting of only A’s and T’s will bend differently from a sequence of G’s and C’s. An important consequence of this mechanical layer of information is the positioning of nucleosomes. Nucleosomes consist of 147 base pairs of DNA wrapped around a protein core, like a string around a spool. By either allowing or restricting access to a binding site, a nucleosome may serve as an on/off switch, of which the location is extremely important. A third layer of information on DNA is translation speed. Translation speed refers to the rate at which a protein is created, and it depends on the codons used in a genetic sequence. The research in this thesis investigates how these layers of information are multiplexed. It uses multiple novel approaches, one of them being the use of weighted graphs consisting of all possible DNA sequences to find the very best and very worst nucleosome-attracting sequences. Show less
The elasticity of the DNA double helix varies with the underlying base pair sequence. This allows one to put mechanical cues into sequences that in turn influence the packaging of DNA into... Show moreThe elasticity of the DNA double helix varies with the underlying base pair sequence. This allows one to put mechanical cues into sequences that in turn influence the packaging of DNA into nucleosomes, DNA-wrapped protein cylinders. Nucleosomes dictate a broad range of biological processes, ranging from gene regulation, recombination, and replication to chromosome condensation. Here we map base pair sequences onto graphs and use shortest paths algorithms to determine which DNA stretches are easiest or hardest to bend inside a nucleosome. We further demonstrate how genetic and mechanical information can be multiplexed by studying paths through graphs of synonymous codons. Using this method we find that nucleosomes can be placed by mechanical cues nearly everywhere on the genome of baker's yeast (Saccharotnyces cerevisiae). Show less
