Email updates

Keep up to date with the latest news and content from BMC Evolutionary Biology and BioMed Central.

Open Access Highly Accessed Research article

The impact of RNA structure on coding sequence evolution in both bacteria and eukaryotes

Wanjun Gu1*, Musheng Li2, Yuming Xu2, Ting Wang3, Jae-Hong Ko4* and Tong Zhou3*

Author Affiliations

1 Research Center for Learning Sciences, Southeast University, Nanjing, Jiangsu 210096, China

2 School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China

3 Department of Medicine, University of Arizona, Tucson, AZ 85721, USA

4 Department of Physiology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea

For all author emails, please log on.

BMC Evolutionary Biology 2014, 14:87  doi:10.1186/1471-2148-14-87

Published: 23 April 2014



Many 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.


We 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.


We 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.

mRNA structure; Purifying selection; Synonymous mutation; Translation initiation; Codon usage bias; Gene expression