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Large-scale turnover of functional transcription factor bindingsites in Drosophila

Journal Article · · PLoS Computational Biology

The gain and loss of functional transcription-factor bindingsites has been proposed as a major source of evolutionary change incis-regulatory DNA and gene expression. We have developed an evolutionarymodel to study binding site turnover that uses multiple sequencealignments to assess the evolutionary constraint on individual bindingsites, and to map gain and loss events along a phylogenetic tree. Weapply this model to study the evolutionary dynamics of binding sites ofthe Drosophila melanogaster transcription factor Zeste, using genome-widein vivo (ChIP-chip) binding data to identify functional Zeste bindingsites, and the genome sequences of D. melanogaster, D. simulans, D.erecta and D. yakuba to study their evolution. We estimate that more than5 percent of functional Zeste binding sites in D. melanogaster weregained along the D. melanogaster lineage or lost along one of the otherlineages. We find that Zeste bound regions have a reduced rate of bindingsite loss and an increased rate of binding site gain relative to flankingsequences. Finally, we show that binding site gains and losses areasymmetrically distributed with respect to D. melanogaster, consistentwith lineage-specific acquisition and loss of Zeste-responsive regulatoryelements.

Research Organization:
COLLABORATION - UCBerkeley
DOE Contract Number:
AC02-05CH11231
OSTI ID:
913276
Report Number(s):
LBNL--61357; BnR: 400412000
Journal Information:
PLoS Computational Biology, Journal Name: PLoS Computational Biology Journal Issue: 10 Vol. 2
Country of Publication:
United States
Language:
English