Big fish of genetics helps human gene hunt.
Humans were the first animals with a backbone to have their DNA read letter by letter. The runner-up is a fat, poisonous puffer fish, better known in sushi restaurants.
The virtually complete genome of Fugu rubripes is revealed this week alongside a comparison with the human sequence1. "I'm pleased we got there second," says Greg Elgar of the UK Human Genome Mapping Project Resource Centre in Hinxton, part of the international sequencing consortium.
Fugu's similarity to humans and trim genome, not its toxic flesh and spiny, inflatable body, give it scientific eminence. Puffer fish have roughly the same number and types of genes as humans - but they pack them into a string of DNA one-eighth the size because they have less junk DNA.
Fugu's pocket-sized genome should help to resolve contentious estimates of human gene number - it is easier for computer prediction programs to scan Fugu than human DNA for genes. Current estimates reckon we have 30,000 to 40,000 genes. Based on Fugu, "40,000 is your top whack", says Elgar.
Fugu's sequence has also helped unearth nearly 1,000 new human genes. Comparisons with the upcoming mouse and zebrafish genomes should tease even more information from the human sequence. "These will be very exciting times," says consortium member Samuel Aparicio of the University of Cambridge, UK.
Human and fish genes are largely similar because they were inherited from a common ancestor that lived 450 million years ago. But since then, almost a quarter of both species' genes have evolved so much that counterparts are almost unrecognizable, the team found. Genes involved in physiology and laying out a body plan are similar; those behind the immune system are not.
Out of sequence
The pioneering geneticist Sydney Brenner first championed the inflatable Fugu more than a decade ago. Elgar recalls arriving in Brenner's Cambridge lab: "He pulled out this plastic bag of [fish] and said, 'here's your PhD'."
>It was a casualty of the Human Genome Project Greg Elgar , UK Human Genome Mapping Project
The fish soon swam into the scientific spotlight. Its modest sequence was thought to be a more realistic target than the seemingly insurmountable task of charting the human genome. "It really was considered more straightforward than the human," says Aparicio.
But soon the human project caught the scientific imagination and financial support. Fugu was sidelined. "It's a bit ironic," says Elgar. "It was a casualty of the Human Genome Project." When Fugu's sequencing effort finally got under way in 2000, the now-experienced researchers cracked its genome in only a year.
And Fugu's future looks bright: consortium members are now attempting to identify critical sections of DNA, shared by human and fish, that control how a gene makes protein. Control regions for disease genes could become a new target for drugs. Ultimately, "_Fugu_ delivered", says Aparicio.
Aparacio, S. et al. Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Sciencexpress, published online doi:10.1126/science.1072104 (2002).
UK Human Genome Mapping Project
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Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Nature (2002). https://doi.org/10.1038/news020722-10