Ultraconserved Elements in the Human Genome
Abstract
There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.
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We thank the Genome Sequencing Consortia for the human, mouse, rat, dog, chicken, and other genome sequences we used in this analysis; W. Miller, M. Diekhans, A. Hinrichs, K. Rosenbloom, D. Thomas, and the members of the University of California Santa Cruz (UCSC) browser team for providing the genome alignments and other tracks of genome annotation available on the UCSC genome browser; M. Blanchette, S. Salama, T. Lowe, M. Ares, K. Pollard, and B. Cohen for helpful discussions; A. Siepel for the neutral substitution rate analysis involving chicken and chimp; K. Roskin for the calculation of the percent identity in ancestral repeat sites for 1-Mb windows; and S. Walton for help in preparing the manuscript. G.B., W.J.K., and D.H. were supported by National Human Genome Research Institute grant 1P41HG02371 and National Cancer Institute contract 22XS013A, and D.H. was additionally supported by the Howard Hughes Medical Institute. S.S., M.P., I.M., and J.S.M. were supported by the Australian Research Council and the Queensland State Government.
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Science
Volume 304 | Issue 5675
28 May 2004
28 May 2004
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American Association for the Advancement of Science.
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Received: 19 March 2004
Accepted: 27 April 2004
Published in print: 28 May 2004
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