Previous Pause Next
Home >> Resource Center >> Publication >> Editorial >>
Genomics: Big is beautiful PDF Print E-mail
User Rating :  / 0
Thursday, 19 March 2009 09:27


Finding gene regulators in the fruitfly Drosophila melanogaster has proved difficult: looking for conserved non-coding DNA sequences, a method that works well in vertebrates, has been unsuccessful. Michael Eisen at the University of California, Berkeley, and his co-workers suggest that this is because the fly's genome is compact — not because its regulatory architecture differs substantially from that of vertebrates.


Eisen's group sequenced various loci from four species of tephritid — 'true' fruitflies — which have large genomes containing islands of conserved non-coding DNA sandwiched between unconserved stretches. This allowed the researchers to pinpoint six conserved tephritid non-coding regions that functioned as gene enhancers in D. melanogaster embryos. Until now, the compact size of the D. melanogaster genome has been considered a boon to scientists.


The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new vertebrate enhancers. However, these methods have not contributed significantly to the identification of regulatory sequences in sequenced invertebrate taxa. We demonstrate here that this differential success, which is often attributed to fundamental differences in the nature of vertebrate and invertebrate regulatory sequences, is instead primarily a product of the relatively small size of sequenced invertebrate genomes. We sequenced and compared loci involved in early embryonic patterning from four species of true fruit flies (family Tephritidae) that have genomes four to six times larger than those of Drosophila melanogaster. Unlike in Drosophila, where virtually all non-coding DNA is highly conserved, blocks of conserved non-coding sequence in tephritids are flanked by large stretches of poorly conserved sequence, similar to what is observed in vertebrate genomes. We tested the activities of nine conserved non-coding sequences flanking the even-skipped gene of the teprhitid Ceratis capitata in transgenic D. melanogaster embryos, six of which drove patterns that recapitulate those of known D. melanogaster enhancers. In contrast, none of the three non-conserved tephritid non-coding sequences that we tested drove expression in D. melanogaster embryos. Based on the landscape of non-coding conservation in tephritids, and our initial success in using conservation in tephritids to identify D. melanogaster regulatory sequences, we suggest that comparison of tephritid genomes may provide a systematic means to annotate the non-coding portion of the D. melanogaster genome. We also propose that large genomes be given more consideration in the selection of species for comparative genomics projects, to provide increased power to detect functional non-coding DNAs and to provide a less biased view of the evolution and function of animal genomes.

Article link: PLoS ONE 4, e4688 (2009)


Add comment  |   Add to my library  |  Forward this article

login to leave comment