DNA helix: the importance of being GC-rich.

A new explanation for the emergence of heavy (GC-rich) isochores is proposed, based on the study of thermostability, bendability, ability to B-Z transition and curvature of the DNA helix. The absolute values of thermostability, bendability and ability to B-Z transition correlated positively with GC content, whereas curvature correlated negatively. The relative values of these parameters were determined as compared to randomized sequences. In genes and intergenic spacers of warm-blooded animals, both the relative bendability and ability to B-Z transition increased with elevation of GC content, whereas the relative thermostability and curvature decreased. The usage of synonymous codons in GC-rich genes was also found to augment bendability and ability to B-Z transition and to reduce thermostability of DNA (as compared to synonymous codons with the same GC content). The analysis of transposable elements (Alu and B2 repeats in the human and mouse) showed that the level of their divergence from the consensus sequence positively correlated with relative bendability and ability to B-Z transition and negatively with relative thermostability. The bendability and ability to B-Z transition are known to relate to open chromatin and active transcription, whereas curvature facilitates chromatin condensation. Because heavy isochores are known to be gene-rich and show a high level of transcription, it is suggested here that isochores arose not as an adaptation to elevated temperature but because of a certain grade of general organization and correspondingly advanced level of genomic organization, reflected in genome structuring, with physical properties of DNA in the gene-rich regions being optimized for active transcription and in the gene-poor regions for chromatin condensation ('transcription/grade' concept).