title: Intraspecies sequence comparisons for annotating genomes.
abstract: Analysis of sequence variation among members of a single species offers a potential approach to identify functional DNA elements responsible for biological features unique to that species. Due to its high rate of allelic polymorphism and ease of genetic manipulability, we chose the sea squirt, Ciona intestinalis, to explore intraspecies sequence comparisons for genome annotation. A large number of C. intestinalis specimens were collected from four continents, and a set of genomic intervals were amplified, resequenced, and analyzed to determine the mutation rates at each nucleotide in the sequence. We found that regions with low mutation rates efficiently demarcated functionally constrained sequences: these include a set of noncoding elements, which we showed in C. intestinalis transgenic assays to act as tissue-specific enhancers, as well as the location of coding sequences. This illustrates that comparisons of multiple members of a species can be used for genome annotation, suggesting a path for the annotation of the sequenced genomes of organisms occupying uncharacterized phylogenetic branches of the animal kingdom. It also raises the possibility that the resequencing of a large number of Homo sapiens individuals might be used to annotate the human genome and identify sequences defining traits unique to our species.
authors.affiliation: US Dept. of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.
authors.forename: Dario
authors.initials: D
authors.lastname: Boffelli
authors.forename: Claire V
authors.initials: CV
authors.lastname: Weer
authors.forename: Li
authors.initials: L
authors.lastname: Weng
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lewis
authors.forename: Malak I
authors.initials: MI
authors.lastname: Shoukry
authors.forename: Lior
authors.initials: L
authors.lastname: Pachter
authors.forename: David N
authors.initials: DN
authors.lastname: Keys
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002938:Ciona intestinalis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D019143:Evolution, Molecular; D051858:Forkhead Transcription Factors; D005809:Genes, Regulator / Q000235:genetics; D014644:Genetic Variation; D016678:Genome; D016013:Likelihood Functions; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors