The large extent of putative secondary nucleic acid structure in random nucleotide sequences or amino acid derived messenger-RNA

Summary

Random nucleotide sequences were examined to determine how much base pairing might be inferred using current methods of seeking potential secondary structure. A random amino sequence and the human alpha hemoglobin variant Constant Spring were also examined to discover how much additional base pairing might be allowed when some nucleotide positions were ambiguous due to the degeneracy of the genetic code. It was found that: 1. random nucleotide sequences permitted an average of 58 per cent base pairing, only 10.7 per cent of which were GU; 2. amino acid sequences permitted structures with 80 per cent base pairing; 3. use of the degeneracy to optimize base pairing created a bias in favor of configurations in which the first nucleotide position of a codon was paired with another first position nucleotide as well as some other biases; 4. contrary to a claim in the literature, the proposed secondary structure of the MS2 viral coat protein gene shows evidence of having used the degeneracy of the genetic code to optimize base pairing; and 5. again contrary to claims in the literature, one cannot predict with any confidence the secondary structure of messenger RNA from amino acid sequences, even when the presence of extensive numbers of variants are known and the amino acid sequences of other orthologous proteins are also available.