CSCE 496/896 Project Idea: Hunting for Skewed Oligomers

Last modified Tuesday, 16-Aug-2011 14:55:05 CDT
Due date for proposals: Nov. 6

Due date for project write-ups: Dec. 11

Skewed oligomers are short nucleotide sequences that are overrepresented in a genome and that show strand bias. In many prokaryotic genomes, the occurrence of skewed oligomers appears to be a conserved phenomenon, although the actual sequences of the oligomers are highly variable across different species (see Salzberg, S., A. Salzberg, A. Kerlavage, and J.-F. Tomb. 1998. Skewed Oligomers and Origins of Replication. Gene, 217:1-2). In organisms where the skewed oligomer phenomenon occurs, the strand bias shifts very abruptly at or near the experimentally defined or predicted origin and terminus of replication, suggesting that the oligomers play a role in DNA replications. Indeed, in E. coli, many of the skewed oligomers on the lagging strand of replication share a CAG sequence motif and it has recently been demonstrated that CAG is the preferred sequence that is recognized by DNA primase, the enzyme that synthesizes RNA primers for reinitiating DNA synthesis on the lagging strand (see Bhattacharyya S and M.A. Griep. 2000. DnaB helicase affects the initiation specificity of Escherichia coli primase on single-stranded DNA templates. Biochemistry, 39(4): 745-52). Since the CAG motif is not shared by many of the skewed oligomers from other species, it appears that DNA primase specificity may not be highly conserved. In species where there are few or no skewed oligomers, it may be that their DNA primases do not show preference for a given sequence or that another mechanism is employed to prime reinitiation of lagging strand DNA synthesis.

Although the skewed oligomer phenomenon is conserved in many prokaryotic organisms, it has not been reported whether the phenomenon occurs in eukaryotes. In eukaryotes, DNA replication is initiated from multiple origins, however DNA replication on the lagging strand is still discontinuous and therefore must be reinitiated. Given the availability of complete genome sequences of yeast, fly, worm, and complete sequences for many of the human chromosomes, and the description of the algorithm for identifying skewed oligomers:

  1. Determine whether the skewed oligomer phenomenon occurs in eukaryotic chromosomes.

  2. If the phenomenon does occur, is the distribution of oligomers similar among different chromosomes for a given species constant or is there some bias favoring the abundance of certain oligomers on a given chromosome?

  3. How conserved are the sequences of skewed oligomers among yeast, fly, worm, and human chromosomes?

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