Abstract
Investigation of the ar-C midline enhancer of sonic hedgehog orthologs and paralogs from distantly related vertebrate lineages identified lineage-specific motif changes; exchanging motifs between paralog enhancers resulted in the reversal of enhancer specificity.
Highlights
Cis-regulatory modules of developmental genes are targets of evolutionary changes that underlie the morphologic diversity of animals
Phylogenetic footprinting can predict conserved cis-regulatory modules (CRMs) of genes that span over a number of transcription factor binding sites
We were able to predict the motifs that are required for the tissue-specific activity of the paralog enhancers, and we identified the putative transcription factor binding sites that were the likely targets of evolutionary changes underlying the functional divergence of the two ar-C enhancers of the shh paralogs
Summary
Cis-regulatory modules of developmental genes are targets of evolutionary changes that underlie the morphologic diversity of animals. An elaborate alternative model, called duplicationdegeneration-complementation (DDC), has been proposed by Force and coworkers [15] to explain the retention of duplicated paralogs that occurs during evolution Their model is based on the (often) multifunctional nature of genes, which is reflected by the multitude of regulatory elements specific to a particular expression domain. Mutations in subsets of regulatory elements in either one of the duplicated paralogs may result in postduplication spatial and temporal partitioning of expression patterns (subfunctionalization) between them. As a result, both paralogs can fulfil only a subset of complementary functions of the ancestral gene, and will be retained by selection and not be lost secondarily (for review [16])
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