Evolutionary origin of expandable G-C-rich triplet repeat DNA sequences.

A model explaining properties exhibited by fragile-X DNA systems arises from observations that time-dependent base substitutions are expressed at G-C sites but not at A-T sites (Biochem. Genet. 32:383, 1994). [CGG]n sequences are classified as most sensitive to evolutionary base substitution processes involving time-dependent populating of G-C sites with enol-imine states having enhanced stability. Increased density of these states in oocyte DNA would introduce a ground-state collapse double-helix of reduced energy that would inhibit strand separation by the replicase. Evolutionarily altered G' in CG'G triplets allows CG'G to be transcribed as CTG, an initiation codon. And this will cause reinitiation of DNA synthesis, thereby adding additional CGG units to the collapsed double helix. This situation would not occur in slower-evolving male haploid DNA that replicates frequently.