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doi:10.1534/genetics.106.057919
A more recent version of this article appeared on July 1, 2006.
REGULAR RESEARCH PAPERS |
Evolutionary Divergence of Exon Flanks: A Dissection of Mutability and Selection
Yi Xing 1, Qi Wang 1 and Christopher Lee 1*
1 UCLA
* To whom correspondence should be addressed. E-mail: leec{at}mbi.ucla.edu.
Submitted on March 6, 2006
Revised on April 17, 2006
Accepted on 1 May 2006
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 manuscript 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.
Key Words: alternative splicing, evolution, exon flanks, mutation rate, selection pressure
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