Stems and Loops

Abstract

Transcription of DNA generates single-stranded RNAs that may operate by virtue of their structures (tRNAs, rRNAs), or by virtue of their encoding of proteins (mRNAs). The former consist of a small number of types which, while quantitatively abundant, are collectively encoded by a small part of genomes. The latter consist of a large number of types which, while each is quantitatively sparse, are collectively encoded by a larger part of genomes. All types of RNA fold into highly significant (non-random) ‘stem-loop’ structures. While the selective forces affecting tRNA and rRNA structures mainly relate to their roles in the cytoplasm, those affecting mRNA structures largely relate to the need for structure (stem-loop potential) of the genes from which they were transcribed. This need may conflict with the need to optimize the sequence of an encoded protein. Since non-genic regions of genomes also have potential for highly significant stem-loop structure, the potential is likely to be a genome-wide response to some selective force. In 1972 Harold White proposed that the strain of an unwinding force acting on regular duplex DNA would be relieved by extrusion of stem-loop structures. The potentials for such higher ordered structures in single-stranded nucleic acids may be calculated from the base-pairing energies of overlapping dinucleotides, which are fundamental units of nucleic acid structure. Contributions to the energetics of such structures decompose into base composition-dependent and base order-dependent components that may either support or oppose each other. The latter, most important, component is determined by subtracting the base composition-dependent component from the total folding energy. The base composition-dependent component is itself determined by shuffling and refolding a sequence several times – thus destroying the base order-dependent component – and then taking the average folding energy of the resulting structures. Extrusion symmetry between the two strands of a DNA duplex is violated in regions rich in A and C (with complements T and G). Selection for nucleic acid structure provides an explanation for PR2.

I am puzzled by the frequent appearance of palindromes in these sequences. Naturally one would expect occasional short ones by chance, but they seem to occur too often. … I have wondered if there is any mechanism which would produce them, but have been unable to think of one.

F. Crick , 1974 [1]