Eukaryotes Genomes - RATTUS NORVEGICUS

Rattus norvegicus is more commonly known as the brown rat or Norwegian rat. It is not a native of Norway, as its name suggests. The species originated in Asia, reached Europe by the mid-1500's and arrived in North America in about 1775 on ships from England. This cosmopolitan rat can now be found in nearly every part of the world. It is associated with human habitation in all major cities of the world. Chiefly found in areas around human settlement, Norway rats occur wherever there is an abundance of food and shelter, from the subways and crowded tenements of metropolitan districts, to the corn and grain fields of farm country . The Norway rat is a coarse-furred rat with prominent, naked ears and nearly naked scaly tail which is shorter than the head and body. Molars of the upper jaw have tubercles in three longitudinal rows, as in the house mouse. General colour is brown/dark grey with scattered black hairs, while underparts are pale grey or greyish brown, the average length from nose to tip of tail is 400 mm while the tail is 187 mm.

Rats are among the most prolific of all mammals and will breed throughout the year, although fewer litters are produced in the winter. Each female becomes receptive for a period of about 20 hours every 4-6 days. Gestation is from 21-23 days, but it may be prolonged when a pregnant female is nursing an earlier litter. Litters usually contain between 2 and 14, but the average number is 7offspring. Females experience a postpartum estrus, often mating within 18 hours of giving birth and thus easily produce 6-8 litters per year. Rats continue to breed until they are 1.5-2 years old. In captivity Norway rats may live to be 4 years old. Their average lifespan is probably about 2 years. They are omnivorous and have a prodigious appetite, one can eat a third of its weight in twenty-four hours. Their main constraint is that they cannot go long without water unless their diet contains other liquids in adequate amounts. Dominance hierarchies within a group of rats are based on size/weight rather than age. Generally rats are nocturnal, although some can often be found foraging during the daytime. These diurnal rats are generally socially low-ranked individuals who have been denied access to food by dominant rats during the night, when most of the activity takes place.

Many consider this rat to be the greatest mammal pest of all time. It has caused more deaths than all the wars in history. It harbours lice and fleas and has been the source of bubonic plague, typhus, trichina, infectious jaundice and many other serious diseases. Rats are usually a contributing factor of first importance in the spread of pandemics during war. They also cause considerable damage to property including crops, depletion and pollution of human food stores, and damage to buildings and their contents from destructive chewing of wiring, pipes, and walls. There is also considerable evidence of rats attacking helpless human beings, especially infants. Paradoxically, although the rat is a nuisance to most people, it is beloved by researchers who study human diseases such as heart disease, diabetes, and addiction, and also by those who develop drugs to treat these disorders.

Rats were established as a model for learning about human physiology and disease in the early 1800s. In the 1900s, they ceded some of their popularity to mice, which are smaller, quicker to breed and easier to manipulate genetically however rat research is now experiencing a renaissance. Rats are easier to work with, they are less aggressive than mice, they don't scurry around so much; mice are slow and inflexible learners whereas rats are quick learners and make good subjects for behavioural studies. Size also plays an important role as researchers particularly appreciate the rat's relatively generous proportions, which make it easy to carry out detailed physiological measurements. Rats are biologically similar to humans, for example rat heart beats at less than two-thirds the rate of a mouse and is closer to the average human resting rate of 70 beats per minute. In stressed rats, the areas of the brain that change size are the same as those thought to be affected by stress in people. Rats are susceptible to many of the same health problems, and they have short life-cycles so they can easily be studied throughout their whole life-span or across several generations. In addition, scientists can easily control the environment around the animal (diet, temperature, lighting, etc.), which would be difficult to do with humans.

Rat research covers so many different parameters it would be impossible to list all, however some areas include:

In 2003 the first cloned rat was produced by injecting adult DNA into a cultured egg, the technique will help pave the way for the production of genetically modified rats where key genes can be altered when required. In 2002 scientists produced "remote controlled" rats by embedding electrodes in the brain and could guide the animal left and right, other signals stimulated the reward centre providing incentive to follow the instructions. Rats have for a long time been associated with "spare part surgery" and have donated and received transplants of skin, heart, marrow, liver, bowel, pancreas and brain tissue allowing researchers to identify and combat issues involved with rejection. In drug development, the rat is employed to demonstrate therapeutic efficacy and assess toxicity of novel drug compounds before human clinical trials and for the future better rat models will decrease drug failure in clinical trials - currently standing at about 90% - which will decrease development costs and time to market.

Now that scientist have been able to produce "knockout" rats, (a genetic trick that allows scientists to disrupt specific genes to study how the genes function in rats) these insights can then be applied to human disease research. Although knockout mice have been a staple of research for some time, the knockout rat is sometimes a better model for human diseases.

The "draft" sequence of the rat genome was made publicly available in early 2004 and it is 90 percent complete. To sequence the remaining 10 percent of the genome-stretches of DNA that are difficult to decipher-would cost more than government agencies are prepared to spend at the moment. The rat genome is smaller than the human genome, but larger than the mouse genome, and all three organisms probably have a similar number of genes, roughly 25,000 to 30,000. Scientists interested in evolution now have genomes of three mammals to compare and contrast. Having three genomes should help scientists learn more about how we evolved from a common ancestor about 80 million years ago. By comparing the finished reference sequence of the human genome with genomes of other organisms, researchers can identify regions of similarity and difference. This information can help scientists better understand the structure and function of human genes and thereby develop new strategies to combat human disease. Comparative genomics also provides a powerful tool for studying evolutionary changes among organisms, helping to identify genes that are conserved among species, as well as genes that give each organism its unique characteristics.

References:

J. Mol. Evol. 57:3-12(2003)
http://animaldiversity.ummz.umich.edu/site/accounts/information/Rattus_norvegicus.html
http://www.nature.com/nature/focus/ratgenome/
http://www.bioinformatrix.com/net/modules.php?name=News&file=article&sid=656
http://www.genomenewsnetwork.org/articles/2004/03/31/rat_genome.php