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Intraspecies sequence comparisons for annotating genomes

Boffelli, Dario and Weer, Claire V. and Weng, Li and Lewis, Keith D. and Shoukry, Malak I. and Pachter, Lior and Keys, David N. and Rubin, Edward M. (2004) Intraspecies sequence comparisons for annotating genomes. Genome Research, 14 (12). pp. 2406-2411. ISSN 1088-9051. PMCID PMC534664. doi:10.1101/gr.3199704.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle Research Data
Pachter, Lior0000-0002-9164-6231
Additional Information:© 2004 Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, Received May 18, 2004; accepted in revised form October 5, 2004. We thank Shigeki Fujiwara, Arjan Gittenberger, Kevin Heasman, Helene Huelvan, Di Jiang, Shungo Kano, Aimee Phillippi, Andy Sexton, and Seb Shimeld for providing C. intestinalis samples. Research was conducted at the E.O. Lawrence Berkeley National Laboratory and at the Joint Genome Institute, with support by grants from the Programs for Genomic Application, NHLBI (E.M.R.) and NIH (L.P.), and performed under Dept. of Energy Contract DE-AC0378SF00098, Univ. of California. GenBank accession numbers: Forkhead region: AY667314–AY667347. Snail region: AY667371–AY667407. Col5a1 region: AY667278–AY667313. Patched region: AY667348–AY667370.
Funding AgencyGrant Number
National Heart, Lung, and Blood InstituteUNSPECIFIED
Department of Energy (DOE)DE-AC03-78SF00098
Issue or Number:12
PubMed Central ID:PMC534664
Record Number:CaltechAUTHORS:20170308-131651119
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Official Citation:Intraspecies sequence comparisons for annotating genomes Dario Boffelli, Claire V. Weer, Li Weng, Keith D. Lewis, Malak I. Shoukry, Lior Pachter, David N. Keys, and Edward M. Rubin Genome Res. December 2004 14: 2406-2411; Published in Advance November 15, 2004, doi:10.1101/gr.3199704
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74911
Deposited By: George Porter
Deposited On:08 Mar 2017 21:27
Last Modified:15 Nov 2021 16:29

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