RNA secondary structure: a comparison of real and random sequences

(Received 23 July 1992, accepted in final form 23 September 1992)

Abstract
A sample of transfer RNA molecules is compared to a sample of random sequences having the same length and same percentage composition of the different bases. For each sequence all possible secondary structures are constructed and a distribution of free energies for the states is obtained. It is found that the ground state free energies of tRNA molecules are significantly lower than for random sequences, and that tRNA molecules have significantly fewer alternative secondary structures at energies close to the ground state than do random sequences. A distance D is defined which measures the average difference between molecular configurations and the ground state configuration. At realistic temperatures of order 300 K this distance is much larger for random sequences than for tRNA sequences. Thus the secondary structure of tRNA molecules at finite temperature is more stable than for random sequences. Sequences are considered which differ by a small number of mutations from real tRNA sequences. On average mutations destabilize the secondary structure. This suggests that a stable secondary structure is one of the factors selected for by natural selection. The thermodynamic behaviour of RNA sequences is compared to models for random heteropolymers which have a low temperature frozen phase.