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 unp ublished sources. We have developed 'Exofish', a procedure based on homolog y searches, to identify human genes quickly and reliably. This method relie s on the sequence of another vertebrate, the pufferfish Tetraodon nigroviri dis, to detect conserved sequences with a very low background. Similar to F ugu rubripes a marine pufferfish proposed by Brenner et al.(3) as a model f or genomic studies, T. nigroviridis is a more practical alternative(4) with a genome also eight times more compact than that of human. Many comparison s have been made between F. rubripes and human DNA that demonstrate the pot ential of comparative genomics using the pufferfish genome(5). Application of Exofish to the December version of the working draft sequence of the hum an genome and to Unigene showed that the human genome contains 28,000-34,00 0 genes, and that Unigene contains less than 40% of the protein-coding frac tion of the human genome.