Evolution of regulatory sequences in 12 Drosophila species.

PLoS Genetics
Jaebum KimSaurabh Sinha

Abstract

Characterization of the evolutionary constraints acting on cis-regulatory sequences is crucial to comparative genomics and provides key insights on the evolution of organismal diversity. We study the relationships among orthologous cis-regulatory modules (CRMs) in 12 Drosophila species, especially with respect to the evolution of transcription factor binding sites, and report statistical evidence in favor of key evolutionary hypotheses. Binding sites are found to have position-specific substitution rates. However, the selective forces at different positions of a site do not act independently, and the evidence suggests that constraints on sites are often based on their exact binding affinities. Binding site loss is seen to conform to a molecular clock hypothesis. The rate of site loss is transcription factor-specific and depends on the strength of binding and, in some cases, the presence of other binding sites in close proximity. Our analysis is based on a novel computational method for aligning orthologous CRMs on a tree, which rigorously accounts for alignment uncertainties and exploits binding site predictions through a unified probabilistic framework. Finally, we report weak purifying selection on short deletions, providing ...Continue Reading

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Methods Mentioned

BETA
ChIP

Software Mentioned

liftOver
Pecan
FlyReg
ProbconsMorph
Indelign
âProbconsMorphâ
REDfly
âPecanâ
Probcons
Paml

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