Conservation of regulatory elements between two species of Drosophila.
BACKGROUND
One of the important goals in the post-genomic era is to determine the regulatory elements within the non-coding DNA of a given organism's genome. The identification of functional cis-regulatory modules has proven difficult since the component factor binding sites are small and the rules governing their arrangement are poorly understood. However, the genomes of suitably diverged species help to predict regulatory elements based on the generally accepted assumption that conserved blocks of genomic sequence are likely to be functional. To judge the efficacy of strategies that prefilter by sequence conservation it is important to know to what extent the converse assumption holds, namely that functional elements common to both species will fall within these conserved blocks. The recently completed sequence of a second Drosophila species provides an opportunity to test this assumption for one of the experimentally best studied regulatory networks in multicellular organisms, the body patterning of the fly embryo.


RESULTS
We find that 50%-70% of known binding sites reside in conserved sequence blocks, but these percentages are not greatly enriched over what is expected by chance. Finally, a computational genome-wide search in both species for regulatory modules based on clusters of binding sites suggests that genes central to the regulatory network are consistently recovered.


CONCLUSIONS
Our results indicate that binding sites remain clustered for these "core modules" while not necessarily residing in conserved blocks. This is an important clue as to how regulatory information is encoded in the genome and how modules evolve.
Emberly
Eldon
E
Center for Studies in Physics and Biology, The Rockefeller University, 1230 York Avenue, New York, NY, USA. eemberly@edsc.rockefeller.edu
Rajewsky
Nikolaus
N
Siggia
Eric D
ED
D000465:Algorithms; D000818:Animals; D001482:Base Composition / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D017124:Conserved Sequence / Q000235:genetics*; D030541:Databases, Genetic; D004330:Drosophila / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D017344:Genes, Insect / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods / Q000706:statistics & numerical data; D013045:Species Specificity
D005819:Genetic Markers