Comparative analyses of multi-species sequences from targeted genomic regions

• Published in: Nature Vol. 424; no. 6950; pp. 788 - 793
• Main Authors: Green, E. D, Thomas, J. W, Touchman, J. W, Blakesley, R. W, Bouffard, G. G, Beckstrom-Sternberg, S. M, Margulies, E. H, Blanchette, M, Siepel, A. C, Thomas, P. J, McDowell, J. C, Maskeri, B, Hansen, N. F, Schwartz, M. S, Weber, R. J, Kent, W. J, Karolchik, D, Bruen, T. C, Bevan, R, Cutler, D. J, Schwartz, S, Elnitski, L, Idol, J. R, Prasad, A. B, Lee-Lin, S.-Q, Maduro, V. V. B, Summers, T. J, Portnoy, M. E, Dietrich, N. L, Akhter, N, Ayele, K, Benjamin, B, Cariaga, K, Brinkley, C. P, Brooks, S. Y, Granite, S, Guan, X, Gupta, J, Haghighi, P, Ho, S.-L, Huang, M. C, Karlins, E, Laric, P. L, Legaspi, R, Lim, M. J, Maduro, Q. L, Masiello, C. A, Mastrian, S. D, McCloskey, J. C, Pearson, R, Stantripop, S, Tiongson, E. E, Tran, J. T, Tsurgeon, C, Vogt, J. L, Walker, M. A, Wetherby, K. D, Wiggins, L. S, Young, A. C, Zhang, L.-H, Osoegawa, K, Zhu, B, Zhao, B, Shu, C. L, De Jong, P. J, Lawrence, C. E, Smit, A. F, Chakravarti, A, Haussler, D, Green, P, Miller, W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 14.08.2003; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Chromosomes, Human, Pair 7 - genetics; Comparative analysis; Conserved Sequence - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; DNA Transposable Elements - genetics; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Genes. Genome; Genome; Genomics; Humans; Mammals - genetics; Molecular and cellular biology; Molecular genetics; Mutagenesis - genetics; Phylogeny; Sequence Alignment; Sequence Homology, Nucleic Acid; Species Specificity; Vertebrates; Vertebrates - genetics; Vertebrata; Species; Genomics; Comparative study
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01858

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.