Roughly 200 years after being tamed, bred and adopted as science’s favourite laboratory animal, the brown Norway rat has had its genome sequenced. It is only the third mammal after humans and mice to have its genetic plan read. Researchers say the feat will allow important human genes to be tracked down more quickly, for example those related to cardiovascular disease or behaviour, and will speed the creation of treatments for diseases. Comparisons between the genomes is also yielding tantalising insights into how each species evolved. The analysis has already shown, for example, that rats have been evolving faster than both humans and mice. “We find that rodent evolution is an order of magnitude faster than in humans,” says Richard Gibbs of the Baylor College of Medicine in Houston, Texas, and head of the sequencing effort.
The regions evolving fastest are those associated the rat’s acute sense of smell and its use in detecting danger, marking territory and choosing mates. Rats have an estimated 2070 smell receptor genes, about a third more than mice, and also make more “pheromone” scents. Rats have also zoomed ahead in the evolution of genes that help them detoxify chemicals in their livers and elsewhere. “Rats occur in smelly sewer pipes and yucky places, as compared with the mouse living in nice clean fields, and that fits the model of how their genes develop,” Gibbs says.
< By "knocking out" genes, it might be possible to genetically engineer rats so that their detox machinery is identical to ours, improving the predictive accuracy of toxicology and drug safety testing. Similarities between the human and rat genomes are as important as the differences. Researchers were relieved to find that almost all the human genes linked with disease so far are identical in rats too, validating the use of rats in their experiments. The availability of the draft rat genome, covering 90 per cent of its genetic code, should accelerate research on the genetic roots of inherited disorders in humans. “The identification of disease genes will in many cases be five fold quicker with a [rat] genome sequence,” says Kerstin Lindblad-Toh, at MIT’s Whitehead Institute in Cambridge Massachusetts. Rattus norvegicus, mistakenly classified in 1769 as an emigrant from Norway rather than its native Asia, turns out to have 2.75 billion pairs of DNA bases. That is slightly fewer than our 2.9 billion and slightly more than the mouse’s 2.6 billion. The genome analysis, by 20 institutions from six countries, showed that humans, rats and mice have about the same number of genes. It also reveals that humans and rodents went our separate ways from a common ancestor about 80 million years ago, with rats and mice diverging between 12 and 24 million years ago. Even today, all three species share 280 large chunks of chromosomes that are virtually identical, suggesting that they are indispensable. These one billion or so bases form what the DNA sequencers call an “ancestral core”. Asked what was next on the genome sequencers’ agenda, Gibbs told New Scientist, that the preliminary DNA code for the cow is expected in the summer, and that of the rhesus macaque monkey in the next 12 months. Journal reference: Nature (vol 428, p 493) NewScientist.com news service
31 March 04