Natural selection is not required to explain universal compositional patterns in rRNA secondary structure categories

We have encountered an unexpected property of rRNA secondary structures that may generalize to all RNAs. Analysis of 8892 ribosomal RNA sequences and structures from a wide range of species revealed unexpected universal compositional trends. First, different categories of rRNA secondary structure (stems, loops, bulges, and junctions) have distinct, characteristic base compositions. Second, the observed patterns of variation are similar among sequences from large and small rRNA subunits and all domains of life, despite extensive evolutionary divergence. Surprisingly, these differences do not seem to be related to selection for different compositions in different structural categories, but rather relate to the overall composition of the molecule: Randomized RNAs with no evolutionary history show the same structure-dependent compositional biases as rRNAs. These compositional trends may improve the accuracy of RNA secondary structure prediction, because they allow us to compare predicted structures against known compositional preferences. They also suggest caution in interpreting differences in the rate of change of the GC content in different parts of the molecule as evidence of differential selection.