A tryst, then the power to resist

Surprising cross-breeding has helped some mice to survive warfarin poisoning

Mighty Mouse may have gotten a very important superpower — resistance to widespread rodent poisons — through some mistaken-identity sex.

BORROWER SPECIES One house mouse from Europe looks much like another from the outside, but some can resist a widespread class of rodent poisons thanks to a stretch of DNA inherited from a different species. Stefan Endepols

Since the rat poison warfarin and others in its class of rodenticides went into use in the middle of the last century, various populations of mice and rats have turned up with abilities to survive exposure, explains evolutionary biologist Michael Kohn of Rice University in Houston. He and a U.S.-German research group have now found that some of the house mice (Mus musculus domesticus) in Germany and Spain take their resistance from a key gene’s alternative version that came from a completely different species.

In the history of the house mice, at least one “desperate, lonely mouse,” as Kohn puts it, mated with an Algerian mouse (Mus spretus), a species whose range extends into Iberia and southern France. This interspecific pairing doesn’t produce a lot of reproductively successful offspring. Yet the strong evolutionary force of widespread poison drove borrowed resistance genetics from the Algerian mouse to spread among house mice, the researchers report in the August 9 Current Biology.

The borrowed version of this gene, called vkorc1, isn’t the only genetic shield against warfarin that Mus musculus domesticus  can employ. Other poison-proof versions arose from mutations that occurred over generations within the house mouse species. That double source for possible protection makes this tale of evolution in action even more interesting, Kohn says. It’s the first occasion he can think of where scientists have a chance to study the same basic trait evolving by two different paths in the same species. That trait in the case of mice depends on the enzyme that vkorc1 encodes, which helps recycle vitamin K for blood clotting. Warfarin works by disrupting the process of clotting and is also prescribed in gentler formulations as a blood thinner for people. Some of the mutations that arise in vkorc1 protect animals from fatally excessive blood thinning.

Just how the Algerian mouse acquired its protection is not clear, but Kohn notes older research showing that species from arid areas often have evolved unusual clotting genes, possibly driven by shortages of vitamin K.

Crossbreeding within the same species has been at the heart of farming and gardening for centuries, but hybridization of different species to create fertile offspring is more problematic. Genetic barriers tend to slow or block abundant mixing — or else the two species wouldn’t stay separate.

Yet two species can hybridize in nature. Kinds of bacteria mix and swap important genes for resisting antibiotics, and botanists have come to recognize important crosses between plant species. “Though over the past 15 years or so there has been a growing appreciation for the evolutionary significance of hybridization, there are still those who hold onto a paradigm that denies such a role for genetic exchange,” says evolutionary biologist Michael Arnold of the University of Georgia in Athens. Zoologists have been particularly hard to convince, he says, so he’s especially pleased to see such an example in mice.

Hybridizing might actually be fairly common among animal species, comments evolutionary biologist Nick Barton of the Institute of Science and Technology Austria near Vienna. But it’s certainly rare for scientists to know what version of a gene that hybridization has moved between species and what evolutionary forces drove the gene’s spread. “In fact, I can’t think of another example,” he says.

Susan Milius is the life sciences writer, covering organismal biology and evolution, and has a special passion for plants, fungi and invertebrates. She studied biology and English literature.

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