Intra-species sequence comparisons for annotating genomes

Journal Article · Thu Jul 15 04:00:00 EDT 2004 · Genome Research

DOI:https://doi.org/10.1101/gr.3199704· OSTI ID:838983

Boffelli, Dario ^[1]; Weer, Claire V; Weng, Li; Lewis, Keith D; Shoukry, Malak I; Pachter, Lior; Keys, David N; Rubin, Edward M

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1. LBNL Library

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 intra-species sequence comparisons for genome annotation. A large number of C. intestinalis specimens were collected from four continents and a set of genomic intervals 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 and 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. The sequence data from this study has been submitted to GenBank under accession nos. AY667278-AY667407.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE. Office of Management Budget and Evaluation; National Institute of Health, National Heart Lung and Blood Institute. Genomic Application (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 838983
• Report Number(s): LBNL--56499
• Journal Information: Genome Research, Journal Name: Genome Research Journal Issue: 12 Vol. 14
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ANIMALS
DNA
FUNCTIONALS
GENETICS
MUTATIONS
NUCLEOTIDES
SEAS