Introduction

The Japanese pufferfish, Fugu rubripes ('torafugu'), has the smallest genome among vertebrates. In a landmark paper published in 1993 (Brenner et al., 1993), Dr Sydney Brenner and his team showed that the genome of the pufferfish is only 400 Mb which is about eight times smaller than the 3 Gb human genome. It was found to contain a similar repertoire of genes to humans, and is devoid of dispersed repetitive elements such as SINES and LINES. They proposed Fugu as a model vertebrate genome to understand the more complex human genome and other vertebrate genomes. Subsequent studies have shown that the intergenic regions and introns in the Fugu are highly compressed and uncluttered with repetitive sequences; the average gene density is about one gene per 10 kb and the gene order over short range is conserved between the Fugu and human genomes. The gene prediction algorithms developed for the human genome have proved to be very efficient for identifying genes in the Fugu because of the highly conserved gene structure between the Fugu and humans, short introns (modal value ~80 bp) and absence of 'junk' sequence that adds to the noise in gene prediction. Thus Fugu is a vertebrate model of choice for gene discovery and gene validation in humans and other vertebrates.

Fugu is also an excellent model for identifying and characterizing gene regulatory elements. Since the intergenic and intronic regions are compact, it is easy to scan the non-coding sequences of the Fugu for identifying conserved putative regulatory elements. Transgenic work in rodents has shown that mammalian trans factors are able to interact with cis acting elements of Fugu genes to mediate cell and tissue specific expression, and response to physiological stimuli. Since a Fugu cosmid clone contains 6 to 8 genes and a BAC contains 10 to 15 genes, Fugu genomic clones are useful for dissecting locus control regions in cell line and transgenic experiments.

The common ancestors of Fugu and humans diverged about 450 million years ago and a comparison between the two genomes provides interesting insight into the evolutionary changes that have shaped the two distant vertebrates. Several differences in the genomic organization of the two genomes such as additional introns, gene and locus duplications, inversions, etc. have been identified. Since these changes are the result of rare genetic events, they are being used as unambiguous molecular markers to identify branch points in vertebrate evolution.

Some Key Publications