This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gr.3199704v1 14/12/2406    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boffelli, D. Articles by Rubin, E. M. Search for Related Content PubMed PubMed Citation Articles by Boffelli, D. Articles by Rubin, E. M. Social Bookmarking                   What's this?

Letter

Intraspecies sequence comparisons for annotating genomes

¹ US Dept. of Energy Joint Genome Institute, Walnut Creek, California 94598, USA ² Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA ³ Department of Mathematics, University of California, Berkeley, Berkeley, California 94720, USA

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.

⁴ Corresponding author.
E-mail emrubin{at}lbl.gov; fax (510) 486-4229.

[Supplemental material is available online at www.genome.org. The sequence data from this study were submitted to GenBank under accession nos. AY667278–AY667407. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: S. Fujiwara, A. Gittenberger, K. Heasman, H. Huelvan, D. Jiang, S. Kano, A. Phillippi, A. Sexton, and S. Shimeld.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. A. Campbell, W. Zhu, N. Jiang, H. Lin, S. Ouyang, K. L. Childs, B. J. Haas, J. P. Hamilton, and C. R. Buell Identification and Characterization of Lineage-Specific Genes within the Poaceae Plant Physiology, December 1, 2007; 145(4): 1311 - 1322. [Abstract] [Full Text] [PDF]

				M. Marcet-Palacios, M. Ulanova, F. Duta, L. Puttagunta, S. Munoz, D. Gibbings, M. Radomski, L. Cameron, I. Mayers, and A. D. Befus The Transcription Factor Wilms Tumor 1 Regulates Matrix Metalloproteinase-9 through a Nitric Oxide-Mediated Pathway J. Immunol., July 1, 2007; 179(1): 256 - 265. [Abstract] [Full Text] [PDF]

				S. J. Macdonald and A. D. Long Joint Estimates of Quantitative Trait Locus Effect and Frequency Using Synthetic Recombinant Populations of Drosophila melanogaster Genetics, June 1, 2007; 176(2): 1261 - 1281. [Abstract] [Full Text] [PDF]

				L. Caputi, N. Andreakis, F. Mastrototaro, P. Cirino, M. Vassillo, and P. Sordino Cryptic speciation in a model invertebrate chordate PNAS, May 29, 2007; 104(22): 9364 - 9369. [Abstract] [Full Text] [PDF]

				L. Banihashemi, G. M. Wilson, N. Das, and G. Brewer Upf1/Upf2 Regulation of 3' Untranslated Region Splice Variants of AUF1 Links Nonsense-Mediated and A+U-Rich Element-Mediated mRNA Decay Mol. Cell. Biol., December 1, 2006; 26(23): 8743 - 8754. [Abstract] [Full Text] [PDF]

				L. Elnitski, V. X. Jin, P. J. Farnham, and S. J.M. Jones Locating mammalian transcription factor binding sites: A survey of computational and experimental techniques Genome Res., December 1, 2006; 16(12): 1455 - 1464. [Abstract] [Full Text] [PDF]

				N. E. Schlick, M. I. Jensen-Seaman, K. Orlebeke, A. E. Kwitek, H. J. Jacob, and J. Lazar Sequence analysis of the complete mitochondrial DNA in 10 commonly used inbred rat strains Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1183 - C1192. [Abstract] [Full Text] [PDF]

				A. Mortazavi, E. C. L. Thompson, S. T. Garcia, R. M. Myers, and B. Wold Comparative genomics modeling of the NRSF/REST repressor network: From single conserved sites to genome-wide repertoire Genome Res., October 1, 2006; 16(10): 1208 - 1221. [Abstract] [Full Text] [PDF]

				I. Dupanloup and H. Kaessmann Evolutionary simulations to detect functional lineage-specific genes Bioinformatics, August 1, 2006; 22(15): 1815 - 1822. [Abstract] [Full Text] [PDF]

				W. Shi, M. Levine, and B. Davidson Unraveling genomic regulatory networks in the simple chordate, Ciona intestinalis Genome Res., December 1, 2005; 15(12): 1668 - 1674. [Abstract] [Full Text] [PDF]

				L. Flaherty, B. Herron, and D. Symula Genomics of the future: Identification of quantitative trait loci in the mouse Genome Res., December 1, 2005; 15(12): 1741 - 1745. [Abstract] [Full Text] [PDF]

				G. G. Loots and I. Ovcharenko Dcode.org anthology of comparative genomic tools Nucleic Acids Res., July 1, 2005; 33(suppl_2): W56 - W64. [Abstract] [Full Text] [PDF]

				A. L. Caicedo and M. D. Purugganan Comparative Plant Genomics. Frontiers and Prospects Plant Physiology, June 1, 2005; 138(2): 545 - 547. [Full Text] [PDF]