Evolution of the secondary structures and compensatory mutations of the ribosomal RNAs of Drosophila melanogaster

This paper examines the effects of DNA sequence evolution on RNA secondarystructures and compensatory mutations. Models of the secondary structuresof Drosophila melanogaster 18S ribosomal RNA (rRNA) and of the complexbetween 2S, 5.8S, and 28S rRNAs have been drawn on the basis of comparativeand energetic criteria. The overall AU richness of the D. melanogasterrRNAs allows the resolution of some ambiguities in the structures of bothlarge rRNAs. Comparison of the sequence of expansion segment V2 in D.melanogaster 18S rRNA with the same region in three other Drosophilaspecies and the tsetse fly (Glossina morsitans morsitans) allows us todistinguish between two models for the secondary structure of this region.The secondary structures of the expansion segments of D. melanogaster 28SrRNA conform to a general pattern for all eukaryotes, despite having highlydivergent sequences between D. melanogaster and vertebrates. The 70 novelcompensatory mutations identified in the 28S rRNA show a strong (70%) biastoward A-U base pairs, suggesting that a process of biased mutation and/orbiased fixation of A and T point mutations or AT-rich slippage-generatedmotifs has occurred during the evolution of D. melanogaster rDNA. Thisprocess has not occurred throughout the D. melanogaster genome. Theprocesses by which compensatory pairs of mutations are generated and spreadare discussed, and a model is suggested by which a second mutation is morelikely to occur in a unit with a first mutation as such a unit begins tospread through the family and concomitantly through the population.Alternatively, mechanisms of proofreading in stem-loop structures at theDNA level, or between RNA and DNA, might be involved. The apparenttolerance of noncompensatory mutations in some stems which are otherwisestrongly supported by comparative criteria within D. melanogaster 28S rRNAmust be borne in mind when compensatory mutations are used as a criterionin secondary-structure modeling. Noncompensatory mutation may extend to theproduction of unstable structures where a stem is stabilized by RNA-protein or additional RNA-RNA interactions in the mature ribosome. Ofmotifs suggested to be involved in rRNA processing, one (CGAAAG) isstrongly overrepresented in the 28S rRNA sequence. The data are discussedboth in the context of the forces involved with the evolution of multigenefamilies and in the context of molecular coevolution in the rDNA family inparticular.