Abstract
BackgroundMany studies have found functional RNA secondary structures are selectively conserved among species. But, the effect of RNA structure selection on coding sequence evolution remains unknown. To address this problem, we systematically investigated the relationship between nucleotide conservation level and its structural sensitivity in four model organisms, Escherichia coli, yeast, fly, and mouse.ResultsWe define structurally sensitive sites as those with putative local structure-disruptive mutations. Using both the Mantel-Haenszel procedure and association test, we found structurally sensitive nucleotide sites evolved more slowly than non-sensitive sites in all four organisms. Furthermore, we observed that this association is more obvious in highly expressed genes and region near the start codon.ConclusionWe conclude that structurally sensitive sites in mRNA sequences normally have less nucleotide divergence in all species we analyzed. This study extends our understanding of the impact of RNA structure on coding sequence evolution, and is helpful to the development of a codon model with RNA structure information.
Highlights
Many studies have found functional RNA secondary structures are selectively conserved among species
To understand the effect of RNA structure conservation on coding sequence evolution, we systematically investigated the relationship between nucleotide conservation level and Messenger RNA (mRNA) secondary structure in four model organisms, including one prokaryote and three eukaryotes, E. coli, Saccharomyces cerevisiae (S. cerevisiae), Drosophila melanogaster (D. melanogaster), and Mus musculus (M. musculus)
To avoid the confounding factors caused by the selection on nonsynonymous sites, only the 4-fold degenerate sites in coding sequences were investigated in this study, which means we focused on the synonymous sites without any nonsynonymous mutational opportunity
Summary
Many studies have found functional RNA secondary structures are selectively conserved among species. The effect of RNA structure selection on coding sequence evolution remains unknown. To address this problem, we systematically investigated the relationship between nucleotide conservation level and its structural sensitivity in four model organisms, Escherichia coli, yeast, fly, and mouse. Unlike the studies we mentioned above, the main issue addressed in the second group of studies is the effect of RNA secondary structure change caused by a single-point mutation. A more recent study investigated accumulated mutations in Escherichia coli (E. coli) genes over 40,000 generations of evolution, and found mutations that may disrupt mRNA secondary structure are selectively filtered out in the course of evolution [28]
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