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

Abstract

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genome is unknown, with estimates ranging from 50,000 to 90,000 (refs 1, 2), and to more than 140,000 according to unpublished sources.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. as a model for genomic studies, T. nigroviridis is a more practical alternative 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 genome. 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.

The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla

“…Several resources were used to build V. vinifera gene models automatically with GAZE 28 . We used predictions of repetitive regions by repeatscout 33 , conserved coding regions predicted by the exofish method 34,35 , genewise 36 alignments of proteins from Uniprot 37 , Geneid 38 and Snap 39 ab initio gene predictions, and alignments of several cDNA resources (Supplementary Information).…”

Genome evolution and biodiversity in teleost fish

“…The sequence of T. nigroviridis has been used to predict the number of genes in the human genome (Roest Crollius et al, 2000). Importantly, hundreds of putative novel human genes have been discovered by comparing the pufferfish and human genome sequences (Aparicio et al, 2002;Jaillon et al, 2004).…”

“…The pufferfishes Takifugu rubripes (Torafugu) and Tetraodon nigroviridis (spotted green pufferfish) are pure genomics models. They are studied because of the compactness of their genome, characterized by small intronic and intergenic regions (Brenner et al, 1993;Roest Crollius et al, 2000), but at the moment these animals cannot be crossed routinely in the laboratory and are not usable in vivo for functional analysis of gene function. Finally, cichlids from the great lakes of East Africa, sticklebacks and guppies (Poecilia reticulata) are important models to study the molecular basis of speciation and the evolutionary mechanisms shaping development and behaviour (Peichel et al, 2001;Brooks, 2002;Verheyen et al, 2003;Kocher, 2004;Shapiro et al, 2004).…”

Timing and mechanism of ancient vertebrate genome duplications – the adventure of a hypothesis

“…This fourfold difference and the observed 1:4 relationship between many Drosophila and human genes (1:4 rule) [15][16][17] was an additional argument in favor of two rounds of WGD under the assumption that no subsequent gene loss had happened. The estimation that the human genome might contain as few as 25 000 genes [18][19][20][21][22] signaled that if there had been WGDs, they must have been followed by extensive gene loss; therefore, finding evidence for old duplications might not be as straightforward as originally thought.…”