Colloque

Bioinformaticists Reinvent the Wheel?

Donald R. Forsdyke

Membre a labase

Donald R. Forsdyke

Résumé du colloque

Before modern sequencing and computational technology appeared, various biochemical techniques provided genomic information which is now being rediscovered/reinvented in various forms by bioinformaticists. In the 1950s and 1960s Chargaff presented his four " rules " on base composition : 1. The first parity rule for duplex DNA (%A=%T; %C=%G). 2. The cluster rule (significant associations of pyrimidines or purines in clusters). 3. The second parity rule, namely that the first parity rule applies, to a close approximation, to single-stranded DNA. 4. The GC rule (the GC% is species specific). The first parity rule gained instant recognition as the Watson-Crick model, but the others have received less attention. The cluster rule was elaborated by Szybalski's laboratory (1966) which showed (1) for leftward-transcribing genes the top strand of DNA (mRNA template strand) has pyrimidine clusters, (2) for rightward-transcribing genes the top strand (mRNA synonymous strand) has purine-clusters, and (3) leftward and rightward-transcribing genes are orientated with respect to the origin of replication. In 1981 the Smithies laboratory showed that cluster biases were reflected in base-composition biases in single-strands of DNA, thus locally violating Chargaff's second parity rule. It follows (1) that mRNAs (exons), whether transcribed from leftward or rightward genes, tend to be purine-loaded, and (2) that the purine-clusters are located in the loop regions of mRNAs. Today's bioinformaticists, many coming from informatic rather than biological backgrounds, should note this work, which prepared the ground for recognition that DNA contains multiple, potentially conflicting, levels of information (e.g. stem-loop potential may conflict with coding potential, especially in the case of genes under strong positive Darwinian selection).