The number of genes in the human genome is unknown, with estimates ranging from 50,000 to 90,000 (refs 1, 2), and to more than 140,000 according to unpublished sources. We have developed ‘Exofish’, a procedure based on homology searches, to identify human genes quickly and reliably. This method relies on the sequence of another vertebrate, the pufferfish Tetraodon nigroviridis, to detect conserved sequences with a very low background. Similar to Fugu rubripes , a marine pufferfish proposed by Brenner et al.3 as a model for genomic studies, T. nigroviridis is a more practical alternative4 with a genome also eight times more compact than that of human. Many comparisons have been made between F. rubripes and human DNA that demonstrate the potential of comparative genomics using the pufferfish genome5. Application of Exofish to the December version of the working draft sequence of the human genome and to Unigene showed that the human genome contains 28,000–34,000 genes, and that Unigene contains less than 40% of the protein-coding fraction of the human genome.
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Fields, C., Adams, M.D., White, O. & Venter, J.C. How many genes in the human genome? Nature Genet. 7, 345 –346 (1994).
Antequera, F. & Bird, A. Number of CpG islands and genes in human and mouse. Proc. Natl Acad. Sci. USA 90, 11995–11999 (1993).
Brenner, S. et al. Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome. Nature 366, 265 –268 (1993).
Crnogorac-Jurcevic, T., Brown, J.R., Lehrach, H. & Schalkwyk, L.C. Tetraodon fluviatilis, a new puffer fish model for genome studies. Genomics 41, 177–184 ( 1997).
Elgar, G. et al. Generation and analysis of 25 Mb of genomic DNA from the pufferfish Fugu rubripes by sequence scanning. Genome Res. 9, 960–971 (1999).
Schuler, G.D. et al. A gene map of the human genome. Science 274, 540–546 (1996).
Dunham, I. et al. The DNA sequence of human chromosome 22. Nature 402, 489–495 (1999).
Deloukas, P. et al. A physical map of 30,000 human genes. Science 282, 744–746 (1998).
Roest Crollius, H. et al. Characterization and repeat analysis of the compact genome of the freswater pufferfish Tetraodon nigroviridis. Genome Res . (in press).
Jin, L., Zhong, Y. & Chakraborty, R. The exact numbers of possible microsatellite motifs . Am. J. Hum. Genet. 55, 582– 583 (1994).
Benson, G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 27, 573–580 ( 1999).
Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 ( 1990).
Smith, T.F. & Waterman, M.S. Identification of common molecular subsequences. J. Mol. Biol. 147, 195– 197 (1981).
Glemet, E. & Codani, J. LASSAP, a large scale sequence comparisons package. Comput. Appl. Biosci. 13, 137– 143 (1997).
We thank the sequencing and template preparation team at Genoscope; Sun Microsystems for access to the SUN benchmark centre; and F. Francis for critical reading of the manuscript. This work would not have been possible without the public availability of a large fraction of the sequence of the human genome, and we thank all contributing genome centres.
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