Introns resolve the conflict between base order-dependent stem-loop potential and the encoding of RNA or protein: further evidence from overlapping genes

Many eukaryotic genes are split into exons and introns, the latter bring re moved post-transcriptionally so that only exon sequences appear in cytoplas mic RNAs. Since introns: appear in both protein-encoding RNAs and non-prote in-coding RNAs. they interrupt genetic information per se, not just protein -encoding information. A DNA sequence has the potential to carry more than one type of genetic information, but different types may conflict. Thus, it has been proposed that introns arose because sequences were unable to cont ain concomitantly complete information for the encoding both gf stem-loops and of cytoplasmic products (protein and/or RNA). Stem-loop potential is he ld to be selectively advantageous since it promotes the recombination-depen dent correction of genetic errors. Stem-loop potential, the best local meas ure of which is base order-dependent stem-loop potential, tends to be less in exons than in introns. This is particularly evident in genes evolving ra pidly under positive Darwinian selection, where the protein-encoding functi on is dominant. Evidence is now presented that the rare regions where gents overlap also impose excessive encoding demands so that the concomitant cod ing of base order-dependent stem-loop potential is decreased. Our results a re consistent with the hypothesis that sequences with high stem-loop potent ial arose in the early 'RNA world'. Ancestors of modem genes would have ent ered this world when sequences (exons) encoding cytoplasmic products, were interspersed with sequences (introns) encoding selectively advantageous ste m-loops. Purine-loading pressure would also have favoured intron formation. (C) 2001 Elsevier Science B.V. All rights reserved.