NUCLEIC-ACID SEQUENCES CODING FOR INTERNAL ANTISENSE PEPTIDES - ARE THERE IMPLICATIONS FOR PROTEIN-FOLDING AND EVOLUTION

We have asked whether coding segments of nucleic acids generate amino acid sequences which have an antisense relationship to other amino aci d sequences in the same chain (i.e. 'Internal Antisense'), and if so, could the internal antisense content be related to the structure of th e encoded protein? Computer searches were conducted with the coding se quences for 132 proteins. The result for each search of a specific seq uence was compared to the mean result obtained from 1000 randomly asse mbled nucleic acid chains whose length and base composition were ident ical to that of the native sequences. The study was conducted in all t hree reading frames. The normal reading frame (frame one) was found to be contain lower amounts of internal antisense than the randomly asse mbled chains, whereas the frame two results were much higher. The inte rnal antisense content in frame three was not significantly different from that in the random chains. The amount of internal antisense in fr ames two and three was correlated with the GC content at the center po sition of the codons in that frame, but this correlation was absent in frame one. No correlation with chain length was found. Qualitatively similar results were obtained when the random model was limited to ret ain the same purine/pyrimidine ratio as the native chains at each posi tion in the codons, but in this case the internal antisense in frame t hree was also significantly greater than the computer-generated sequen ces. The results suggest that the internal antisense content in the co rrect reading frame has a qualitatively different origin from that in the other two frames. The high amount in frames two and three is appar ently an artifact resulting from the asymmetric distribution of G and C in the codons, while the low amount in frame one may suggest evoluti onary selection against internal antisense. Thus, the results do not s upport a relationship between internal antisense and protein structure .