Evolution of Functional Structures of RNA

Evolution of new functions for RNA has been crucial to the history of life. New functions could have evolved before the DNA era in RNA molecules capable of replicating or, later, in RNA molecules specified by a DNA genome. Despite the importance of this process during molecular evolution, no one has undertaken a systematic analysis to elucidate the principles and mechanisms involved. Because appearance of a new func-tion would have to be preceded by formation of a new structure, insight can be gained by studying relevant molecular architecture in contempo-rary RNA. In this chapter, I discuss ways in which certain underlying structures of RNA could evolve new functions. Many RNA molecules are multifunctional. Any such molecule has probably evolved through sequential addition of domains that have fa-vorable selective effects on the molecule or on the cell carrying it. Each gained function would represent one manifestation of the basic mecha-nism of evolution within an RNA species. This mechanism can be ap-proached by analysis of multifunctional RNA molecules only, because one cannot imagine the precursors of a monofunctional molecule. One of the best-studied examples of multifunctional RNA is the primer for DNA replication of plasmid ColEl in Escherichia coli. This 555-nucleotide RNA must form a specific folded structure before it can serve as a primer; it consists of four functional domains, each composed of one, two, or three stem-loops. A number of other plasmid species replicate by means of primer RNAs with nucleotide sequences and struc-tures similar to those in ColEl, so a common ancestor is likely. The evolutionary process leading to the ancestral molecule is deduced from the effects of various mutations on the structure and function of the ColEl primer RNA and from comparisons of structures among the re-lated primers. The ancestral molecule probably evolved by sequential ad-dition of stem-loop structures on which new functions arose