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Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation

Authors: Hare, Emily E.; Peterson, Brant K.; Iyer, Venky N.; Meier, Rudolf; Eisen, Michael B.;

Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation

Abstract

The gene expression pattern specified by an animal regulatory sequence is generally viewed as arising from the particular arrangement of transcription factor binding sites it contains. However, we demonstrate here that regulatory sequences whose binding sites have been almost completely rearranged can still produce identical outputs. We sequenced the even-skipped locus from six species of scavenger flies (Sepsidae) that are highly diverged from the model species Drosophila melanogaster, but share its basic patterns of developmental gene expression. Although there is little sequence similarity between the sepsid eve enhancers and their well-characterized D. melanogaster counterparts, the sepsid and Drosophila enhancers drive nearly identical expression patterns in transgenic D. melanogaster embryos. We conclude that the molecular machinery that connects regulatory sequences to the transcription apparatus is more flexible than previously appreciated. In exploring this diverse collection of sequences to identify the shared features that account for their similar functions, we found a small number of short (20-30 bp) sequences nearly perfectly conserved among the species. These highly conserved sequences are strongly enriched for pairs of overlapping or adjacent binding sites. Together, these observations suggest that the local arrangement of binding sites relative to each other is more important than their overall arrangement into larger units of cis-regulatory function.

Keywords

evolutionary and comparative genetics, 570, Embryo, Nonmammalian, Genome, Insect, 590, comparative genomics, QH426-470, Animals, Genetically Modified, Evolution, Molecular, developmental biology, computational biology, pattern formation, embryology, Genetics, Animals, Drosophila Proteins, transcriptional regulation, Conserved Sequence, Homeodomain Proteins, Binding Sites, Base Sequence, comparative sequence analysis, Diptera, evolutionary biology, Gene Expression Regulation, Developmental, genetics and genomics, developmental evolution, Enhancer Elements, Genetic, Insect Proteins, Drosophila, Sequence Alignment, Research Article, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
255
Top 1%
Top 10%
Top 1%
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gold