Chargaff’s Cluster Rule

Abstract

The two DNA strands of a gene are the mRNA-synonymous “coding” (codon-containing) strand and the mRNA-template strand. Clusters of clusters of purines are general features of coding strands of DNA, which usually contain an excess of purines (“purine-loading”). Accordingly, since purines pair with pyrimidines, complementary clusters of clusters of pyrimidines are general features of the corresponding template strands, which usually contain an excess of pyrimidines (“pyrimidine-loading”). The clustering of clusters within a gene locally violates Chargaff’s PR2. This permits prediction of transcriptionally active regions in uncharted DNA and, in some cases, the origins and termination sites of DNA replication. RNA transcription and DNA replication appear to proceed optimally when the enzymes performing these functions (polymerases) are moving in the same direction along the DNA template. Since the stems of nucleic acid stem-loop structures require equal numbers of complementary bases, clusters tend to occupy loop regions. Here they would militate against the loop-loop ‘kissing’ interactions that precede the formation of nucleic acid duplexes. Thus, the loading of loops with bases that do not strongly base-pair with each other should decrease unproductive interactions between nucleic acids, so leaving them freer to engage in productive interactions, such as those between mRNAs and tRNAs that are critical for protein synthesis.

Another consequence of our studies on deoxyribonucleic acids of animal and plant origin is the conclusion that at least 60% of the pyrimidines occur as oligonucleotide tracts containing three or more pyrimidines in a row; and a corresponding statement must, owing to the equality relationship [between the two strands], apply also to the purines.

Erwin Chargaff (1963) [1]