Genoscope and Whitehead Announce the Draft Sequence of the Tetraodon Puffer Fish Genome

CAMBRIDGE, Mass. — Chalking up another victory for comparative genomics, researchers from Genoscope (The French National Sequencing Center) in Paris, France, and the Whitehead Institute Center for Genome Research today announced that they have produced a six-fold sequence coverage of Tetraodon nigroviridis, a type of puffer fish whose genome is estimated to be 380 million DNA letters long.

Tetraodon is a freshwater puffer fish that is 20-30 million years distant from the Fugu rubripes, another type of puffer fish whose genome sequence is being announced today by the Department of Energy's Joint Genome Institute. Both fish are considered to be important species to sequence because they are vertebrates and 8 times as compact as the human genome, with the same genes and regulatory content as humans but with much less "junk" DNA. This makes it easier to identify genes in the human.

Together, the two fish sequences will add to the knowledge base researchers need to unravel the mysteries of the human genome. Comparing the human genome to those of other species helps researchers identify important genetic elements conserved through evolution.

The Tetraodon puffer fish sequence represents a 6-fold coverage of its genome; in other words, it covers the length of the Tetraodon genome six times over with overlapping DNA fragments. Whitehead and Genoscope scientists say that they now have enough coverage of the Tetraodon genome to be able to assemble the genome, or determine the exact order of the DNA chemical bases A, T, C, and G along the Tetraodon chromosomes.

The Tetraodon sequences are available online to scientists across the world to look for Evolutionary COnserved REgions (ecore) using a tool called Exofish, which has already been used to help refine the estimate of the number of genes contained in the human genome. Exofish (which stands for EXOn FInding by Sequence Homology) is a genomic comparative method used to identify genes based on the homology or similarities between two species.

In fact, 18 months ago, genome-wide analysis comparing the Tetraodon and the human genome caused Genoscope scientists to propose a first re-evaluation the gene content of the human genome, suggesting that the human genome contains 28,000 to 34,000 genes rather than the previous estimates of 50,000 to 90,000 genes.

The announcement of the sequences of the two different types of puffer fish represents an important progress for the Human Genome Project because this information, along with the genome sequences of other species, will provide researchers key tools to gain insights into the human genome. This information will in turn translate into practical knowledge toward developing better therapies in the future.

Although the recently completed draft sequence of the human genome offers an initial look at the human gene content, to fully unravel the important information from the human genome, scientists will have to compare it to the genome sequences of many other species. That's because evolution preserves the most important genetic information across species; if genes and regulatory elements have survived hundreds of millions of years of evolution, they would be functionally important. But other genes may not have survived evolution because they may no longer be important for survival in the new environment. So researchers need comparative sequences that are both closely and distantly related to humans, because different genetic elements in humans would call for comparison with different species.

So far, scientists have sequenced baker's yeast, the nematode worm, and the fruit fly. They are also racing toward completion of the mouse genome sequence. Also in the works are sequences of many other organisms large and small.

Puffer fish contain essentially the same genes and regulatory sequences as the human genome but they have much less "junk" DNA. As a result, scientists say, finding genes and regulatory sequences in the puffer fish genome will be easier. This in turn will help researchers identify analogous genes and DNA regions in the human genome.

Puffer fish diverged from humans around 400 million years ago. So researchers reason that any genes that survived that length of evolutionary time must be important.



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