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


RESULTS
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.


CONCLUSIONS
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.
Xie
Hai-Bing
HB
State Key Laboratory of Genetic Resource and Evolution, Kunming Institute of Zoology, Kunming 650223, PR China. xiehb03@mail.kiz.ac.cn
Irwin
David M
DM
Zhang
Ya-Ping
YP
D000483:Alleles; D001483:Base Sequence; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D019143:Evolution, Molecular; D005787:Gene Frequency; D053263:Gene Regulatory Networks; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors; D004247:DNA