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Open Access Highly Accessed Research article

Evolution of conserved secondary structures and their function in transcriptional regulation networks

Hai-Bing Xie123, David M Irwin4 and Ya-Ping Zhang12*

Author Affiliations

1 State Key Laboratory of Genetic Resource and Evolution, Kunming Institute of Zoology, Kunming 650223, PR China

2 Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming 650091, PR China

3 The Graduate School, Chinese Academy of Sciences, Beijing 100049, PR China

4 Department of Laboratory Medicine and Pathobiology, University of Toronto, 100 College Street, Toronto, Ont., M5G 1L5, Canada

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BMC Genomics 2008, 9:520  doi:10.1186/1471-2164-9-520

Published: 2 November 2008



Many conserved secondary structures have been identified within conserved elements in the human genome, but only a small fraction of them are known to be functional RNAs. The evolutionary variations of these conserved secondary structures in human populations and their biological functions have not been fully studied.


We searched for polymorphisms within conserved secondary structures and identified a number of SNPs within these elements even though they are highly conserved among species. The density of SNPs in conserved secondary structures is about 65% of that of their flanking, non-conserved, sequences. Classification of sites as stems or as loops/bulges revealed that the density of SNPs in stems is about 62% of that found in loops/bulges. Analysis of derived allele frequency data indicates that sites in stems are under stronger evolutionary constraint than sites in loops/bulges. Intergenic conserved secondary structures tend to associate with transcription factor-encoding genes with genetic distance being the measure of regulator-gene associations. A substantial fraction of intergenic conserved secondary structures overlap characterized binding sites for multiple transcription factors.


Strong purifying selection implies that secondary structures are probably important carriers of biological functions for conserved sequences. The overlap between intergenic conserved secondary structures and transcription factor binding sites further suggests that intergenic conserved secondary structures have essential roles in directing gene expression in transcriptional regulation networks.