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Hybrid Mouse Resistant To Widely Used Poisons

June 03, 2017

Over thousands of years, mice have thrived, despite man's best efforts to stop them. Now they have taken a genetic leap that makes them resistant to widely used poisons. Via two distinct and surprising processes, it appears they have acquired a gene that helps them resist the effects of warfarin, an anticoagulant used as a blood thinner in people but also common in rodent poisons. In a genetic study of how this came about, researchers highlight how humans, first by inventing agriculture and then through pesticide use, drove the process.

Michael Kohn, associate professor of ecology and evolutionary biology at Rice University in Houston, Texas, and colleagues, write about how the the ordinary European house mouse evolved to become poison-resistant in the 9 August issue of Current Biology.

The gene in question is vkorc1. It is present in all mammals and helps them manage vitamin K.

Vkorc1 and various mutations have been researched extensively. Kohn himself has reported a study where one mutation increases the risk of arterial calcification and osteoporosis in humans.

However, it appears that one particular mutation in this gene confers resistance to warfarin in mice.

Kohn and colleagues argue that the mice acquired this mutation via two distinct processes: point mutation and horizontal gene transfer.

They believe the point mutation occured in the Algerian mouse (Mus spretus), which lives in the desert and eats seeds. Point mutation is where DNA spontaneously develops mutations. Imagine copying large volumes of text and making small spelling mistakes in the odd word here and there.

Kohn suggests that for the Algerian mouse, one such spelling "mistake" gave it an advantage: an ability to counter a vitamin K deficiency in its diet. He explained in a statement how point mutation is a "textbook example" of how populations of organisms adapt to new environments.

Rodents breed quickly, and produce several generations for every human generation, so adaptations like this warfarin one can be observed directly during the lifetimes of evolutionary geneticists, said Kohn.

Warfarin began its use as a rodent poison in the 1950s, and by the 1960s, resistant rodents were already appearing.

The second process, horizontal gene transfer, appears to have happened directly from Algerian mice to the European house mouse (Mus musculus domesticus), say the researchers. This is surprising news because we normally only see this process in microbes, not mammals.

This study is the first to document horizontal gene transfer in great detail. Kohn said:

"A key element of this study is that we've caught evolution in the act."

Kohn first got to know about the "hybrid" mouse when a German baker sent him samples of mice he was not able to kill with bromadiolone, a particularly "nasty version of warfarin", said Kohn.

When he tried to sequence the mice for vkorc1, he could not belief what they found: "I said, 'This cannot be a common house mouse. What type of animal did you send me here?'"

He said the gene seemed "out of place". The sequence was identical to that of the Algerian mouse (Mus spretus), which is similar to that of house mice, but the Algerian mouse is not common in Germany.

"We could see that a big chunk of their DNA looked like Mus spretus," said Kohn, "But genetically, these obscure bromadiolone-resistant mice looked like ordinary house mice."

"This is a freaky mouse," he concluded.

The team believe the Algerian mice passed their resistant genome to house mice in Spain or the deserts of North Africa, where the two species overlap.

The main catalyst has been human activity. Thousands of years ago, these two species would never have met. But the advent of agriculture and crop farming brought them together.

Usually, hybridization between species gives sterile offspring, but on rare occasions, such as when it brings survival advantage, such as this, it does not:

"I think we are the first to show this in an animal -- hybridization leads to a combination that is advantageous," said Kohn.

Combined with the appearance of warfarin in rodent poison in the 1950s, the usually doomed hybrids adapted:

"... by exploring the repertoire of mutations in the vkorc1 gene and also by experimenting with a copy of vkorc1 from Mus spretus," explained Kohn.

The finding raises some important questions, such as has this happened once, or lots of times in different places? How easy is it? And is it just a matter of time before we see it in rats?

Kohn said we may now need to accept the fact that animals are just as versatile and adaptable as microbes and plants through hybridization.

He said he was concerned that our desire to kill species only makes them stronger, and this study clearly highlights the role of the "human factor".

"One of the gravest concerns to conservation of biodiversity is the inadvertent spread of invasive species across the globe. In this study, this test came in the form of our desire to extirpate so-called pest species with poisons, which we use to get rid of microbes, bugs, weeds and even some mammals," he added.

Catharine Paddock PhD

View drug information on Warfarin Sodium tablets.