title: Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome.
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.
authors.affiliation: Berkeley Drosophila Genome Project, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Bergman
authors.forename: Barret D
authors.initials: BD
authors.lastname: Pfeiffer
authors.forename: Diego E
authors.initials: DE
authors.lastname: Rincón-Limas
authors.forename: Roger A
authors.initials: RA
authors.lastname: Hoskins
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mungall
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Wang
authors.forename: Brent
authors.initials: B
authors.lastname: Kronmiller
authors.forename: Joanne
authors.initials: J
authors.lastname: Pacleb
authors.forename: Soo
authors.initials: S
authors.lastname: Park
authors.forename: Mark
authors.initials: M
authors.lastname: Stapleton
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wan
authors.forename: Reed A
authors.initials: RA
authors.lastname: George
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: de Jong
authors.forename: Juan
authors.initials: J
authors.lastname: Botas
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rubin
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics; D030541:Databases, Genetic; D004330:Drosophila / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005544:Forecasting; D015321:Gene Rearrangement; D017344:Genes, Insect; D014644:Genetic Variation; D016678:Genome; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA / Q000379:methods; D013045:Species Specificity; D020506:Untranslated Regions / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D020506:Untranslated Regions