Researchers have identified 1 200 new human genes by deciphering the DNA code of the laboratory mouse, a development that will dramatically accelerate the pace of medical research. The mouse is only the second mammal, after the human, to reveal its genetic secrets. With the publication today in Nature of the first studies of the complete text of mouse life, researchers can compare two species separated by 70-million years of evolution.
Mice and humans share the same genes for blood pressure, temperature regulation, bone manufacture, cell division, tissue growth and so on. Of a sample of 700 genes so far linked to human disease, mice share 90%. At any time, around 25-million laboratory mice the world over are answering questions about HIV, obesity, osteoporosis, Down’s syndrome, schizophrenia, diabetes, heart disease, Parkinson’s, breast cancer, leukaemia, malaria and a host of other conditions. To geneticists, the mouse, which goes from infant to parent in just four months, is a simple guidebook to help understand the world of human DNA.
”It’s rather like being dropped in the middle of Tokyo, and asked to figure your way around Tokyo just by newspapers. You need some way to know where you should be going, what is good, what is bad and what is boring in the genome,” said Ewan Birney, of European Bioinformatics Institute in Cambridge. ”You really do need a guidebook to find the shop that will sell Marmite in Tokyo. In a similar way, you really do need a guidebook to find the genes in a genome. And this has been quite a challenging computer problem.”
Even the genomes for small creatures are huge. At 2,9- billion letters, the blueprint for a representative human would fill 200 telephone books. The code for genes is concealed in an alphabet of four ”letters” of DNA that would take 96 years to read out loud. But the genes add up to only a few per cent of the total. Both mice and humans have around 30 000 genes. Only about 300 of these genes are unique to each organism.
Laboratory mice have a special place in medicine: they have been routinely used in laboratories for about 100 years and they are so closely inbred as to be genetically almost indistinguishable from each other. Both mouse and human are descended from a little, scurrying creature that coexisted with the last dinosaurs.
”We are all mammals,” said Allan Bradley, director of the Wellcome Trust Sanger Institute in Cambridge. ”When you got up this morning, you stretched, you washed, you rubbed your eyes and ate your cereal for breakfast. Those are mammalian things. Mice do exactly the same things, except that they wake up at night.”
An international partnership of scientists spent years deciphering the mouse genetic code, publishing its findings freely for the rest of the world. With human and mouse genomes published on the internet, researchers anywhere could pinpoint a gene in minutes rather than weeks.
”The entire biomedical community can for the first time fully use this resource to tackle human diseases,” said Jane Rogers, of the Wellcome Trust Sanger Institute. ”They now have powerful tools that will serve them for many decades to come. We share 99% of our genes with mice, and we even have the genes that could make a tail.”
Simon Festing, of the Association of Medical Charities, said: ”For hundreds of years we have watched curiously as mice run round wheels, press levers or navigate mazes. Finally we have the genetic blueprint that will unveil the mysteries of the mouse and will prove invaluable for medical research.”
Although researchers have been genetically modifying mice for two decades — to answer questions about BSE, explore cancer tumours, or begin embryo stem cell research — they have only been able to identify single genes or a few genes at a time. With the first draft of the 2,5-billion letter mouse text, and the completion of the first draft of the 2,9-billion letter human text in 2000, they have been able to use powerful computing tools to search for DNA sequences that order the manufacture of proteins in the cell or control some important process — in effect, the genes.
The research has revealed 9 000 hitherto unknown genes in the mouse. And comparison of the mouse and human genomes has revealed 1 200 unsuspected genes in humans. The new data will also mean that researchers will be able more accurately to alter mouse genes, for more sophisticated laboratory experiments.
”Until now we have been in effect shooting in the dark,” Mark Boguski, of the Fred Hutchinson cancer research centre in Seattle, Washington, writes in Nature. ”The genome of Mus musculus will provide the necessary illumination.”
The research has already revealed a ”genetic arms race” that has been running for millions of years. Some parts of the mouse genome have evolved faster than others. By studying these accelerated changes, researchers will gain greater insight into how genes work, both in humans and mice. Compared with humans, mice have a superb sense of smell. Also, pregnancy hormones in mice have changed dramatically. Humans have fewer young, and take longer to rear them. Mice have large litters many times a year.
Chris Ponting, of the Medical Research Council, said it was just as important to understand why animals were different as it was to know why they were similar, and just as fascinating to see how animals adapted to their ecological environments.
”Now, though, we can use the new geonome sequences to reveal how conflict has remodelled the animals down to their very genes. When we started to look at mouse proteins, we never imagined that we would see so clearly how evolution has sculpted the mouse’s genome to meet its biological needs.” – Guardian Unlimited (c) Guardian Newspapers Limited 2001