Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation
PLoS Genet, 4 (6):
e1000106 (June 2008)DOI: 10.1371/journal.pgen.1000106
Abstract
The transformation of a fertilized egg into a complex, multicellular organism is a carefully choreographed process in which thousands of genes are turned on and off in specific spatial and temporal patterns that confer distinct physical properties and behaviors on emerging cells and tissues. To understand how an organism's genome specifies its form and function, it is therefore necessary to understand how patterns of gene expression are encoded in DNA. Decades of analysis of the fruit fly <italic>Drosophila melanogaster</italic> have identified numerous regulatory sequences, but have not fully illuminated how they work. Here we harness the record of natural selection to probe the function of these sequences. We identified regulatory sequences from scavenger fly species that diverged from <italic>Drosophila</italic> over 100 million years ago. While these regulatory sequences are almost completely different from their <italic>Drosophila</italic> counterparts, they drive identical expression patterns in <italic>Drosophila</italic> embryos, demonstrating extreme flexibility in the molecular machines that interpret regulatory DNA. Yet, the identical outputs produced by these sequences mean they must have something in common, and we describe one shared feature of regulatory sequence organization and function that has emerged from these comparisons. Our approach can be generalized to any regulatory system and species, and we believe that a growing collection of regulatory sequences with dissimilar sequences but similar outputs will reveal the molecular logic of gene regulation.