Rice University researchers found mice are adept at evolving traits that make them resistant to a particular rodent poison not only through point mutation but also through horizontal gene transfer. Photo: Stefan Endepols/Bayer CropScience AG
Over millennia, mice have thrived despite humanity’s efforts to keep them at
bay. A Rice University scientist argues some mice
have found two ways to achieve a single goal—resistance to common poison.
New research by Michael Kohn and colleagues, reported in Current Biology, analyzes a genetic
mutation that has given the ordinary European house mouse this extraordinary
The gene in question, vkorc1, is present in all mammals and manages vitamin
K. A mutation to vkorc1 makes mice resistant to warfarin, an anticoagulant used
as a blood thinner in people as well as rodent poison.
Kohn, an associate professor of ecology and evolutionary biology at Rice,
said the mice evolved to become poison-resistant following two distinct
processes. In one, point mutation, genes adapt through spontaneous mutations
during DNA replication. Algerian mice (Mus
spretus), a desert-dwelling, seed-eating species, probably acquired the
mutation this way to counter a vitamin K-deficient diet, Kohn says.
Evolution through point mutation is a textbook example of how populations adapt
to new environments, he says. Because rodents reproduce so quickly, their
adaptation to warfarin is one of the few that can be observed directly during
the lifetimes of evolutionary geneticists. The poisons were introduced in the
early 1950s, and poison-resistant rodents began to appear in the 1960s.
The other process, horizontal gene transfer, is generally associated with
microbes, not mammals, and has never been documented at the level of detail the
new paper offers, Kohn says. Here, resistance seems to have been transferred
directly from Algerian mice to European house mice (Mus musculus domesticus).
“A key element of this study is that we’ve caught evolution in the act,”
Mutated vkorc1 has been the subject of many studies, including one by Kohn
that illustrated a downside all too familiar to humans, the risk of arterial calcification
A rodent pest-control specialist treating the basement of a German bakery
found the first evidence that house mice had developed resistance to warfarin.
“He said, ‘I cannot kill these mice with bromadiolone,’ a nasty version of
warfarin,” says Kohn, whose lab was asked to sequence mice for vkorc1. (He
noted pest-control professionals have a variety of weapons to eliminate even
Kohn reacted with disbelief when he looked at the sequences. “I said,
‘This cannot be a common house mouse. What type of animal did you send me
Vkorc1 seemed out of place, he said. “The gene sequence was identical
to Mus spretus, which looks similar
to house mice but does not normally occur in Germany,” he says. “We
could see that a big chunk of their DNA looked like Mus spretus. But genetically, these obscure bromadiolone-resistant
mice looked like ordinary house mice. This is a freaky mouse.”
Kohn and colleagues speculated Algerian mice passed the resistant genome
into house mice in Spain or North Africa deserts, where the species overlap geographically.
“In the very distant past, these mice wouldn’t even meet,” he says.
“With the spread of agriculture thousands of years ago in the Fertile
Crescent, humans brought mice with them—unwillingly. That brought these two
types of mice into contact, and they started doing their thing, hybridizing
here and there.”
Hybridization is usually an evolutionary dead end, because at least 50% of
hybrid offspring mice are sterile. “Nature doesn’t think hybrids are very
useful unless something special happens, such as some sort of environmental
change,” Kohn says. “But on the rare occasion—and I think we are the
first to show this in an animal—hybridization leads to a combination that is
The sudden introduction of warfarin in the 1950s may have triggered the
usually doomed hybrids to further adapt “by exploring the repertoire of
mutations in the vkorc1 gene and also by experimenting with a copy of vkorc1
from Mus spretus,” Kohn says.
“The fundamental question now is: Is this so difficult to accomplish
that it only happened once, or is it so easy that it has happened on numerous
occasions in numerous places?”
Kohn and his colleagues are in a unique position to see which version of
resistance might prevail—point mutation or gene transfer—and whether mice will
suffer the same arterial calcification as the mutant rats in Kohn’s previous
“We may need to embrace the fact that animals are just as versatile as
microbes and plants in developing new traits through hybridization,” says
Kohn, who expressed concern that humans’ desire to kill a species only made the
“The human factor in this study is quite clear,” he says.
“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