Mutational Patterns in RNA Secondary Structure Evolution Examined in Three RNA Families

Anuj Srivastava,Jan Mrázek,Russell L Malmberg,Liming Cai,David Liberles

doi:10.1371/journal.pone.0020484

Abstract

The goal of this work was to study mutational patterns in the evolution of RNA secondary structure. We analyzed bacterial tmRNA, RNaseP and eukaryotic telomerase RNA secondary structures, mapping structural variability onto phylogenetic trees constructed primarily from rRNA sequences. We found that secondary structures evolve both by whole stem insertion/deletion, and by mutations that create or disrupt stem base pairing. We analyzed the evolution of stem lengths and constructed substitution matrices describing the changes responsible for the variation in the RNA stem length. In addition, we used principal component analysis of the stem length data to determine the most variable stems in different families of RNA. This data provides new insights into the evolution of RNA secondary structures and patterns of variation in the lengths of double helical regions of RNA molecules. Our findings will facilitate design of improved mutational models for RNA structure evolution.

Highlights

Molecules of RNA perform biological functions which require that they fold into specific secondary and tertiary structures
The associated base pairing in the double helical region of the RNA molecules is retained via patterns of compensatory mutations across sequences
In addition to determining the mutational patterns that lead to variability within individual stems, we examined variability attributed to each stem by principal component analyses (PCA) of the stem length data

Summary

Introduction

Molecules of RNA perform biological functions which require that they fold into specific secondary and tertiary structures. Conservation of these structures may be as important as, or more important than, sequence conservation during the course of RNA evolution [1,2]. The associated base pairing in the double helical region of the RNA molecules is retained via patterns of compensatory mutations across sequences (covariation). Many structural elements (stem-loops, pseudoknots) are conserved within a given RNA family, there is variation in the presence or absence of certain stem-loops and pseudoknots across evolution, and there is variation in the length of corresponding double-helical regions [5,6,7,8]. The types of variation that might be observable when comparing RNAs include single base substitutions, insertions and deletions, base-pair substitutions and insertions and deletions within a conserved stem, and insertion and deletion of entire secondary structure elements

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