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Last Updated: Wednesday, 31 March 2004, 23:30 GMT 00:30 UK
Rat's 'life code' read by science
By Jonathan Amos
BBC News Online science staff

Brown rat, Nature Picture Library/Susan McMillan
A pest in one setting, a tool to improve human health in another (Image: NPL/Susan McMillan)
Scientists have decoded the rat genome, the biochemical instructions in the rodent's cells that guide the building and maintenance of the animal's body.

It is the third mammalian DNA sequence to be deciphered - humans and mice came first - and will be used by researchers to understand the causes of disease.

It should also give valuable insights into the evolution of all mammals.

The work by an international team led by the US Baylor College of Medicine is reported in the journal Nature.

Better rat models will decrease drug failure in clinical trials
Prof Howard Jacob
The rat was made a priority species to decode because of its importance to medical research.

For nearly 200 years, scientists have used the animal as a "model" on which to test ideas about human biology.

Today, the rat, along with its rodent cousin the mouse, account for more than 80% of all laboratory experiments. Scientists have hundreds of strains of mice and rats that mimic human illnesses.

Quicker development

Now, researchers say the information contained in the rat genome will help produce disease models that are an even closer match for the sick conditions found in humans.

"Rats remain the dominant pre-clinical model of human disease for developing new drugs," said Professor Howard Jacob, from the Medical College of Wisconsin, US, and a senior author on the Nature paper.

RAT DNA - RATTUS NORVEGICUS
DNA (BBC)
The double-stranded DNA molecule is held together by chemical components called bases
Adenine (A) bonds with thymine (T); cytosine(C) bonds with guanine (G)
Groupings of these letters form the "code of life"; there are estimated to be about 2.75bn base pairs in the rat genome wound into 22 distinct bundles, or chromosomes
Written in the DNA are possibly 25,000 genes which rat cells use as templates to make proteins; these sophisticated molecules build and maintain the animal's body
"Better rat models will decrease drug failure in clinical trials - currently standing at about 90% - which will decrease development costs and time to market."

The Rat Genome Sequencing Project Consortium used a strain of a brown Norway rat (Rattus norvegicus) to obtain the genetic information. Two females and a male provided the biological samples for the study.

More than 90% of the rat's DNA has been read, sorted and analysed in what the consortium describes as a "draft". The remaining less than 10% is not thought to contain significant data and no current plans are in place to try to retrieve this information.

The research found the rat genome to be of a similar size to humans and mice - at 2.75 billion "letters", or bases, of DNA. It also contains a comparable number of genes - about 25,000.

And it is clear that most of the genes found in the rat can be seen in the human code, too.

Of rodents and dogs

"If one looks at genes that are basically equivalent, then nine out of 10 are the same," said Professor Chris Ponting, from the UK Medical Research Council's Functional Genetics Unit, who worked on the project.

"The disease genes are nearly all within that 90% - they're conserved between rodents and humans. Therefore, in looking at the biology of human disease genes in rodents, it appears rodents make excellent models," he told BBC News Online.

HOW SOME LAB RATS ARE USED
To practise surgery; to study cancer, diabetes, and cardiovascular disease; to investigate psychiatric disorders, neural regeneration, and space motion sickness
In drug development, the rat is employed to demonstrate therapeutic efficacy and assess toxicity of novel drug compounds before human clinical trials
Some families of genes, though, have been greatly expanded in the rat, including, perhaps not surprisingly, those associated with the ability to emit and sense smells.

There are significant distinctions, also, in the genes of the immune system.

Comparison of the rat code with those of the human and the mouse should allow a remarkable view of mammalian evolution.

The rat data shows about 40% of the modern mammalian genome derives from the last common mammalian ancestor that existed tens of millions of years ago. This "core" DNA encodes nearly all the genes and their regulatory signals, and accounts for the similarities among mammals, such as the basic body plan.

More details about the fundamental biochemistry and evolution of mammals will become apparent when scientists get to compare the human and the rodent codes with those of the soon-to-be finished chimp and dog genomes.

"What we know about the dog is that genetically speaking it is closer to humans than rodents, even though in terms of evolution it is further away," explained Professor Ponting.

"That's to say, the dog lineage split off from the human lineage before rodents - it's just that the rodents' DNA has mutated like crazy since then."



SEE ALSO
Scientists unlock chicken code
02 Mar 04 |  Science/Nature
Canine family histories revealed
14 Feb 04 |  Science/Nature
Rat called Ralph is latest clone
25 Sep 03 |  Science/Nature
'Walkies' through dog genome
25 Sep 03 |  Science/Nature
Human genome finally complete
14 Apr 03 |  Science/Nature
Mouse clues to human genetics
04 Dec 02 |  Science/Nature

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