Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence


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genome is unknown, with estimates ranging from 50,000 to 90,000 (refs 1, 2), and to more than 140,000 according to unpublished sources.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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Figure 1: Construction of Exofish.
Figure 2
Figure 3: Examples of chromosome 22 results.
Figure 4: Distribution of gene and ecores on individual human chromosomes according to the EST physical map8 and Exofish.

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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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Correspondence to Jean Weissenbach.

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