Samuel Aparicio,^21* Jarrod Chapman,³ Elia Stupka,^1* Nik Putnam,³ Jer-ming Chia,¹ Paramvir Dehal,³ Alan Christoffels,¹ Sam Rash,³ Shawn Hoon,¹ Arian Smit,⁴ Maarten D. Sollewijn Gelpke,³ Jared Roach,⁴ Tania Oh,¹ Isaac Y. Ho,³ Marie Wong,¹ Chris Detter,³ Frans Verhoef,¹ Paul Predki,³ Alice Tay,¹ Susan Lucas,³ Paul Richardson,³ Sarah F. Smith,⁵ Melody S. Clark,⁵ Yvonne J. K. Edwards,⁵ Norman Doggett,⁶ Andrey Zharkikh,⁷ Sean V. Tavtigian,⁷ Dmitry Pruss,⁷ Mary Barnstead,⁸ Cheryl Evans,⁸ Holly Baden,⁸ Justin Powell,⁹ Gustavo Glusman,⁴ Lee Rowen,⁴ Leroy Hood,⁴ Y. H. Tan,¹ Greg Elgar,^5* Trevor Hawkins,^3* Byrappa Venkatesh,^1* Daniel Rokhsar,^3* Sydney Brenner^110*

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.

¹ Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609.
² University of Cambridge, Department of Oncology, Hutchison-MRC Research Centre, Cambridge CB2 2XZ, UK.
³ U.S. DoE Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA.
⁴ Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA.
⁵ MRC UK HGMP Resource Centre, Hinxton, Cambridge CB10 1SB, UK.
⁶ Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
⁷ Myriad Genetics Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA.
⁸ Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA.
⁹ Paradigm Therapeutics Ltd., Physiological Laboratory, Cambridge CB2 3EG, UK.
¹⁰ Salk Institute, 10010 North Torrey Pines Road, La Jolla, San Diego, CA 92037-1099, USA.
^*   To whom correspondence and requests for materials should be addressed. E-mail: saa1000{at}cam.ac.uk (S.A.), elia{at}fugu-sg.org (E.S.), gelgar{at}hgmp.mrc.ac.uk (G.E.), trevor.hawkins{at}am.amershambiosciences.com (T.H.), mcbbv{at}imcb.nus.edu.sg (B.V.), dsrokhsar{at}lbl.gov (D.R.), sbrenner{at}salk.edu (S.B.).

   Present address: Amersham Biosciences, 928 East Arques Avenue, Sunnyvale, CA 945085, USA.