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The Japanese pufferfish Fugu rubripes has the shortest known genome of any vertebrate species. As vertebrates, fish and humans share not only the defining characteristic of a backbone, but also many basic anatomical and physiological similarities. The compact Fugu genome contains the same basic vertebrate blueprint as the human genome in a sequence seven times shorter. This difference is primarily due to the scarcity in Fugu of the large repeat-filled tracts that litter the human genome. The relative compactness of the Fugu genome simplifies the detection and analysis of both gene sequences and gene regulatory elements.

Fugu rubripes illustration
"Blue fish," oil painting by Leila Hornick © 2002

The Fugu Genome Project was initiated in 1989 in Cambridge by Sydney Brenner and his colleagues Greg Elgar, Sam Aparicio, and Byrappa Venkatesh. With the impending completion of the Human Genome Project the value of the Fugu genome for comparative purposes was noted and in November 2000 the International Fugu Genome Consortium was formed, headed by the Joint Genome Institute, IMCB Singapore, and the HGMP Cambridge. During the following year, the Fugu genome was sequenced and assembled using the whole genome shotgun method pioneered by Celera Genomics. Fugu is the first vertebrate genome to be publicly sequenced and assembled in this manner, and the first vertebrate genome made publicly available after the human genome. The Consortium is currently proceeding to close and selectively finish the Fugu sequence.

The initial analysis of the Fugu sequence helps illuminate the human genome. By comparing the human and Fugu sequences, common functional elements such as genes and regulatory sequences can be recognized as having been preserved in the two genomes over the course of the 450 million years since the species diverged from their common ancestor. By contrast, non-functional sequences are randomized over this long time period. Over 30,000 Fugu genes have been identified in our analysis. The great majority of human genes have counterparts in Fugu, and vice versa, with notable exceptions including genes of the immune system, metabolic regulation, and other physiological systems that differ in fish and mammals. Nearly 1,000 previously unrecognized human genes are predicted by comparing the two genomes. Remarkable stretches of sequence were found containing dozens of genes whose linkage is conserved between humans and Fugu, shedding light on the large scale evolutionary processes that shape genomes. The analysis of the Fugu genome is ongoing, and promises further insights into genome structure and evolution.