טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentCohanim Amir-Ben
SubjectThe Structural Roles of the Sequence Periodicities
in the DNA
DepartmentDepartment of Biotechnology
Supervisors Professor Yechezkel Kashi
Professor Edward Trifonov


Abstract

The 10 - 11 base periodicity, related to eukaryotic nucleosome structure, was first observed 30 years ago. It was also observed at that time that the nucleosomes occupy specific positions along the DNA This started the quest to determine the sequence rules of nucleosome positioning. Later studies revealed that prokaryotic sequences as well display similar periodicity. In this thesis, computational analyses of genome sequences and nucleosome crystal structures were performed. New insights regarding structural roles of the periodicities and sequence dependent nucleosome positioning are revealed. The customary pattern, that is counter-phase oscillation of AA and TT dinucleotides (hereafter ‘counter-phase pattern’), known to be associated with the nucleosomes, was found to be originating from amino acids patterns residing in amphipathic helices. For eukaryotes, counter-phase patterns across neighboring helices remain coherent (in-phase), in spite of non-helical interruption, thus being suitable for nucleosome formation. In addition to the counter-phase pattern, yeast and other eukaryotic genomes display an in-phase 10.4 base periodicity of AA and TT (hereafter ‘in-phase pattern’), not related to the amphipathic helices, which we consider an additional major nucleosome sequence pattern. In coding regions, the AA\TT in-phase pattern mainly stems from the third codon positions. Thus, the third positions are under selection as opposed to the common belief of neutrality. The average structural period of the nucleosome DNA is determined to be 10.4 bases, as observed both in the sequence and in the crystal structure. That puts an end to an old argument about state of DNA in the nucleosome. Phase-shift anomaly observed in the AA\TT in-phase pattern is interpreted as a reflection of the lengths of linker DNA between neighboring nucleosomes. The periodical patterns of the sequence-dependent DNA organization coexist with other messages in the same sequence. In particular, a strong linkage between nucleosome and protein sequence patterns is demonstrated.