MBE Advance Access published online on January 19, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi090
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1 Center for Studies in Physics and Biology, The Rockefeller University, 1230 York Ave, New York, NY 10021, U.S.A. Phone : 212-327-8835 Fax : 212-327-8544
* To whom correspondence should be addressed. The path by which regulatory sequence can change, yet preserve function, is an important open question for both evolution and bioinformatics. The recent sequencing of two additional species of Drosophila, plus the wealth of data on gene regulation in the fruitfly provides new means for addressing this question. For regulatory sequence, indels account for more base-pairs of change than substitutions (between D. melanogaster and D. yakuba), though they are fewer in number. Using D. pseudoobscura as an outgroup, we can distinguish insertions from deletions (with maximum parsimony criteria), and find a ratio between 1 and 5 (insertions to deletions) that is species dependent and much larger than the ratio of 1/8 for neutral sequence (Petrov and Hartl, 1998). Since neutral sequence is rapidly cleared from the genome, most non-coding regions which preserve their length between D. melanogaster - D. pseudoobscura and have an excess of insertions over deletions, should be functional. A fraction of 15-18% (i.e., more than 20 standard deviations from random expectation) of the regulatory sequence is covered by low copy-number tandem repeats whose repeating unit has average length of 5 - 10 bp, and which occur preferentially (25-45% coverage) in indels. All indels may be due to tandem repeats, if we extrapolate the detection efficiency of the repeat-finding algorithms using the observed point mutation rate between the species we compare. Sequence creation by local duplication accords with the tendency for multiple copies of transcription factor binding sites to occur in regulatory modules. Thus indel events and tandem repeats in particular need to be incorporated into models of regulatory evolution since they can alter the rate at which beneficial variants arise, and should also influence bioinformatic algorithms that parse regulatory sequence into binding sites.
Accepted December 14, 2005
Research Article
Sequence Turnover and Tandem Repeats in cis-Regulatory Modules in Drosophila
Saurabh Sinha, E-mail: saurabh{at}lonnrot.rockefeller.edu
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