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Originally published as Genetics Published Articles Ahead of Print on May 15, 2006.
Genetics, Vol. 173, 1787-1791, July 2006, Copyright © 2006
doi:10.1534/genetics.106.057919
Evolutionary Divergence of Exon Flanks: A Dissection of Mutability and Selection
Yi Xing, Qi Wang and Christopher Lee1
Molecular Biology Institute, Center for Genomics and Proteomics, Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1570
1 Corresponding author: Molecular Biology Institute, Center for Genomics and Proteomics, Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570.
E-mail: leec{at}mbi.ucla.edu
The intronic sequences flanking exon–intron junctions (i.e., exon flanks) are important for splice site recognition and pre-mRNA splicing. Recent studies show a higher degree of sequence conservation at flanks of alternative exons, compared to flanks of constitutive exons. In this article we performed a detailed analysis on the evolutionary divergence of exon flanks between human and chimpanzee, aiming to dissect the impact of mutability and selection on their evolution. Inside exon flanks, sites that might reside in ancestral CpG dinucleotides evolved significantly faster than sites outside of ancestral CpG dinucleotides. This result reflects a systematic variation of mutation rates (mutability) at exon flanks, depending on the local CpG contexts. Remarkably, we observed a significant reduction of the nucleotide substitution rate in flanks of alternatively spliced exons, independent of the site-by-site variation in mutability due to different CpG contexts. Our data provide concrete evidence for increased purifying selection at exon flanks associated with regulation of alternative splicing.
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