Why Sequence Dipterans?

A more accurate and detailed understanding of the evolution of regulatory sequences is critical to contemporary genome research. In order to study the evolution of cis-regulation, this project aims to identify and construct functional models of regulatory sequences from a carefully chosen set of developmental genes. The genes will be selected from three diverse families of flies: Coelopids, Calliphorids, and Asilids. Like the much-studied Drosophila, these are all members of the infraorder Muscomorpha, but they are increasingly distantly diverged from Drosophila. Although the function and expression--and therefore regulation--of target genes appear to be conserved throughout the Muscomorpha, preliminary sequencing has found no recognizable conservation of regulatory sequences. Therefore, to accurately annotate regulatory sequences in each family, a dense, multispecies sequencing strategy will be applied to targeted regions containing the genes of interest. Guided by results from a parallel NIH sequencing effort in Drosophila, researchers will choose 6-10 Diptera species at an evolutionary distance where the sequences are readily alignable and where it will be possible to identify functional regulatory sequences and the transcription factor binding sites of which they are constructed.

Utilizing a fraction of the sequencing capacity necessary to sequence a single additional insect genome, this project will yield multiple models of functionally conserved but highly divergent regulatory sequences. From these it will be possible to answer important questions about the nature of regulatory sequence evolution. The work will provide a rigorous context with which to interpret the data from ongoing comparative sequencing projects and a foundation for studies of the evolution of development that will greatly advance our understanding of the natural world.

CSP project participants: Michael Eisen (proposer, LBNL and Univ. of California, Berkeley), Brian Wiegmann (N. Carolina State Univ.), and Urs Schmidt-Ott and Marty Kreitman (Univ. of Chicago).