The pufferfish Tetraodon nigroviridis has a genome of 350 Mb, the smallest genome known to date in the vertebrates. This characteristic makes it very attractive for genomic studies, and inspired the launching of a sequencing project at Genoscope in 1997.

The principal objective of the sequencing of the Tetraodon genome, at the beginning of the project, was to compare the genomic sequences of this fish with those of humans in order to facilitate the identification of human genes. This comparative genomics approach is based on a simple hypothesis: during the 400 million years that have passed since the separation of the Tetraodon and Mammals lineages, the genomic regions which are constrained by their function - especially the coding sequences - have accumulated fewer mutations and thus diverged more slowly than the other regions. The evolutionary distance which separates us from this fish is sufficiently large to ensure that the introns and intergenic regions will have diverged completely, but is sufficiently short such that the majority of coding sequences will have been conserved for at least part of their length. This contrast thus makes it possible to identify them by comparisons at the whole genome scale (a different use of the genome than that chosen later in the Takifugu project, in which the human-fish comparison was limited to predicted genes).