Robber. House mice (pictured) in Germany and Spain have acquired resistance against a group of widely used rodent poisons through hybridization with the Algerian mouse.


'Bastard' Mouse Steals Poison-Resistance Gene

The word "bastard" is rarely meant as a compliment. But scientists have now shown that hybridization between two animal species can have a big advantage for their offspring. House mice in Germany and Spain have acquired resistance against a group of widely used rodent poisons through hybridization with a different species, the Algerian mouse. The finding suggests hybridization may play a more important role in animal evolution than researchers believed.

Hybridization, the interbreeding of two different species, has long been known to play a role in the evolution of plants, and bacteria can exchange genes encoding antibiotic resistance and other traits with members of other species. "But in animals, hybrids were usually seen as bad, as dead ends of evolution," says Diethard Tautz, director of the Max Planck Institute for Evolutionary Biology in Plön, Germany. Mules—the mostly infertile offspring of male donkeys and female horses—are a classic example. That view has changed in the past few years, however, as research showed animal hybrids to be more common than previously thought.

Biologist Michael Kohn of Rice University in Houston, Texas, became interested in hybridization while studying mice's resistance to warfarin (also known as Coumadin), a drug used in humans to prevent blood clotting that was first used as a rodenticide in the 1950s. Warfarin inhibits a protein called VKOR, which is important for recycling vitamin K, a vital component in blood clotting. But as early as 1964, reports of resistant rodents appeared. There was the obvious textbook explanation: Mutations led to small changes in the gene for VKOR that made warfarin slightly less effective. The animals carrying those mutations were at an advantage wherever the compound was used; over the generations, the changes accumulated and warfarin-tolerant mice emerged.

Kohn realized this was not the whole story when a German house mouse (Mus musculus domesticus) with rodenticide resistance turned out to have a curious genetic signature. "It did not look like a house mouse at all," Kohn says. "At first we thought there might have been a mistake." More detailed genetic studies showed that it was a house mouse carrying a big chunk of DNA from Algerian mice (Mus spretus)—a species known to be naturally resistant to warfarin—on chromosome 7.

Further studies showed that in Spain, where Mus musculus and Mus spretus coexist, 27 of 29 house mice tested carried a version of the VKOR gene that conferred resistance to warfarin and that corresponded entirely or in parts to the gene carried by Mus spretus. In Germany, where Mus spretus does not occur, 16 of 50 house mice also showed this signature, the researchers report today in Current Biology. The team, which included two researchers from Bayer CropScience, a producer of warfarin, says that the mice acquired the resistance gene by lifting it wholesale from Mus spretus.

"We are looking at two species that are 1.5 million to 3 million years removed," Kohn says. Even though the two rodents overlap in parts of Africa and Europe, they don’t usually interbreed—and if they do, all male offspring and some female offspring are sterile. Yet, "that narrow window of a few fertile females must have been enough to leak DNA," Kohn says. The researchers show that the house mice successively lost most of the foreign DNA except for a chunk of DNA that includes the resistance.

The study shows that the role of hybridization in animal evolution has been underestimated, Tautz says. Evolutionary biologist Jerry Coyne of the University of Chicago in Illinois agrees that the paper is important. "It is very well documented, and it shows that hybridization is one more mechanism by which variation arises, that natural selection then acts upon," he says. But because hybridization has mostly negative consequences, Coyne believes it's unlikely to be an important mechanism in animal evolution. "This is big news because it is rare,” he says.