GLOBAL SIMILARITIES IN NUCLEOTIDE BASE COMPOSITION AMONG DISPARATE FUNCTIONAL CLASSES OF SINGLE-STRANDED RNA IMPLY ADAPTIVE EVOLUTIONARY CONVERGENCE

The number of distinct functional classes of single-stranded RNAs (ssR NAs) and the number of sequences representing them are substantial and continue to increase. Organizing this data in an evolutionary context is essential, yet traditional comparative sequence analyses require t hat homologous sites can be identified. This prevents comparative anal ysis between sequences of different functional classes that share no s ite-to-site sequence similarity. Analysis within a single evolutionary lineage also limits evolutionary inference because shared ancestry co nfounds properties of molecular structure and function that are histor ically contingent with those that are imposed for biophysical reasons. Here, we apply a method of comparative analysis to ssRNAs that is not restricted to homologous sequences, and therefore enables comparison between distantly related or unrelated sequences, minimizing the effec ts of shared ancestry. This method is based on statistical similaritie s in nucleotide base composition among different functional classes of ssRNAs. In order to denote base composition unambiguously, we have ca lculated the fraction G+A and G+U content, in addition to the more com monly used fraction G+C content, These three parameters define RNA com position space, which we have visualized using interactive graphics so ftware. We have examined the distribution of nucleotide composition fr om 15 distinct functional classes of ssRNAs from organisms spanning th e universal phylogenetic tree and artificial ribozymes evolved in vitr o. Surprisingly, these distributions are biased consistently in G+A an d G+U content, both within and between functional classes, regardless of the more variable G+C content. Additionally, an analysis of the bas e composition of secondary structural elements indicates that paired a nd unpaired nucleotides, known to have different evolutionary rates, a lso have significantly different compositional biases. These universal compositional biases observed among ssRNAs sharing little or no seque nce similarity suggest, contrary to current understanding, that base c omposition biases constitute a convergent adaptation among a wide vari ety of molecular functions.