Research

Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome

Casey M Bergman^1,9, Barret D Pfeiffer^1,9, Diego E Rincón-Limas^2,6, Roger A Hoskins¹, Andreas Gnirke³, Chris J Mungall⁴, Adrienne M Wang^1,7, Brent Kronmiller^1,8, Joanne Pacleb¹, Soo Park¹, Mark Stapleton¹, Kenneth Wan¹, Reed A George¹, Pieter J de Jong⁵, Juan Botas², Gerald M Rubin^1,4 and Susan E Celniker¹

¹Berkeley Drosophila Genome Project, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA

²Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

³Exelixis Inc., South San Francisco, CA 94080, USA

⁴Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA

⁵Children's Hospital and Research Center at Oakland, Oakland, CA 94609, USA

⁶Current address: Departamento de Biologia Molecular, Universidad Autonoma de Tamaulipas-UAMRA, Reynosa, CP 88740, Mexico

⁷Current address: Department of Physiology, University of California, San Francisco, CA 94143, USA

⁸Current address: Department of Bioinformatics and Computational Biology, Iowa State University, Ames, IA 50011, USA

⁹These authors contributed equally to this work

author email corresponding author email

Genome Biology 2002, 3:research0086.1-0086.20doi:10.1186/gb-2002-3-12-research0086

Published:	30 December 2002

This article is part of a series of refereed research articles from Berkeley Drosophila Genome Project, FlyBase and colleagues, describing Release 3 of the Drosophila genome, which are freely available at http://genomebiology.com/drosophila/.

Subject areas: Evolution, Genome studies, Model organisms, Bioinformatics

Abstract

Background

It is widely accepted that comparative sequence data can aid the functional annotation of genome sequences; however, the most informative species and features of genome evolution for comparison remain to be determined.

Results

We analyzed conservation in eight genomic regions (apterous, even-skipped, fushi tarazu, twist, and Rhodopsins 1, 2, 3 and 4) from four Drosophila species (D. erecta, D. pseudoobscura, D. willistoni, and D. littoralis) covering more than 500 kb of the D. melanogaster genome. All D. melanogaster genes (and 78-82% of coding exons) identified in divergent species such as D. pseudoobscura show evidence of functional constraint. Addition of a third species can reveal functional constraint in otherwise non-significant pairwise exon comparisons. Microsynteny is largely conserved, with rearrangement breakpoints, novel transposable element insertions, and gene transpositions occurring in similar numbers. Rates of amino-acid substitution are higher in uncharacterized genes relative to genes that have previously been studied. Conserved non-coding sequences (CNCSs) tend to be spatially clustered with conserved spacing between CNCSs, and clusters of CNCSs can be used to predict enhancer sequences.

Conclusions

Our results provide the basis for choosing species whose genome sequences would be most useful in aiding the functional annotation of coding and cis-regulatory sequences in Drosophila. Furthermore, this work shows how decoding the spatial organization of conserved sequences, such as the clustering of CNCSs, can complement efforts to annotate eukaryotic genomes on the basis of sequence conservation alone.