Significant Rise in Genetically Resistant "Super Rats"

The UK and mainland Europe is experiencing an extreme rise in poison-resistant rats, according to studies conducted at the University of Huddersfield.

Research team leader and Head of Applied Sciences at the university, Dr Dougie Clarke, stresses that the use of common rat poisons are not effective for many populations of rats in some English and Scottish counties. 
“The fact we've tested 17 counties and every single one of them has got resistant rats was an amazing find to us. We didn't even expect to have every single county having resistant rats.”. The resistance is said to be the cause of natural selection after generations of exposure to rodenticides such as Warafin, Bromodiolone and Difenacoum.

Natural selection has caused mutations in the genomes of European rat populations that make them less susceptible to poisons like Warafin. Although several different mutations are prominent in different populations, the alleles all seem to be dominant. Studies over the past few years have also shown that although the mutant rats are resistant to the poison, they still become Vitamin K deficient. In fact, the resistant homozygous rats are prone to lethal haemorrhages after exposure to Warafin. This is an example of overdominant natural selection, where the heterozygous mutants seem to have the best survival advantage.

The research, funded by several British and European pest control organisations, looks at the VKORC1 gene which codes for the production of a subunit in the protein Vitamin K epoxide reductase. VKOR catalyses the reduction of Vitamin K 2,3-epoxide to Vitamin K, an amine that plays a crucial part in blood coagulation. Rodenticides like Warafin inhibit VKORC1 at it's active site (thought to comprise of 4 cysteine residues and either 1 serine or threonine residue), causing a vitamin K deficiency. Rats exposed to Warafin die from either arterial calcification or mass uncontrolled bleeding.
The genomes in the research were studied through PCR cloning, a technique that uses DNA polymerase and restriction enzymes to amply strands of genetic material. This process is very fast and gives a more accurate, quantitative result. 

The exact results of the study are not yet published, as the full details and methodology have been sent to the government in confidential reports.



Sources:

• http://en.wikipedia.org/wiki/Vitamin_K_epoxide_reductase
• http://www.independent.co.uk/news/uk/home-news/invincible-mutant-superrats-spreading-across-the-uk-9567486.html
• http://www.uscnk.com/directory/Vitamin-K-Epoxide-Reductase-Complex-Subunit-1(VKORC1)-6899.htm
• http://www.sciencemag.org/site/products/pcr.xhtml
• Kohn, M.H., Price, R.E., Pelz, H.J. (2008). A cardiovascular phenotype in warfarin-resistant Vkorc1 mutant rats. Artery Research, 2 (4) 138-147. doi: 0.1016/j.artres.2008.09.002.
• Wadelius, M., Chen, L.Y., Downes, K., Ghori, J., Hunt, S., Eriksson, N. ... Deloukas, P. (2005). Common VKORC1 and GGCX polymorphisms associated with warfarin dose. The Pharmacogenomics Journal, 5 (4) 262-270. doi: 10.1038/sj.tpj.6500313.