Blood brothers - the house mouse and the wild mouse

The gene that protects the house mouse from rat poison came from a mouse of a different biological species

Noam Levitan Galileo

The anticoagulant warfarin (known under the brand name Coumadin) is a drug used to prevent the formation of blood clots, which began its journey in 1948 as rat poison. Warfarin suppresses the activity of a protein called VKORC1, which is necessary for the normal activity of vitamin K. This vitamin is necessary for the activation of several factors that are essential for the clotting process. Due to poisoning with the anticoagulant Verfarin, the coagulation process is damaged and internal bleeding occurs, which eventually causes death. About ten years after the start of using the rat poison, rats and mice resistant to the poison began to appear, similar to bacteria that develop resistance to antibiotics. The resistance developed, unsurprisingly, due to mutations - small changes - in the gene vkorc1 which codes for the creation of the protein of the same name. The lucky rats and mice in which the mutation appeared had an advantage over the other rodents and thus following natural selection the resistance trait spread in the population.

Ten different mutations in the gene are known vkorc1 which confer resistance to warfarin and similar toxins in the house mouse (Mouse muscle). But Ying Song (Song) and her colleagues from Rice University in Texas discovered, in a study published in the scientific journal Current Biology, because the house mice "cheated": four of the changes in the gene came from a wild mouse (mus spretus), a mouse of another biological species living in the western region of the Mediterranean basin.

Song and her colleagues used DNA sequencing to examine house mice from Spain, which live in overlapping areas with the wild mice, and from Germany. The researchers discovered that almost all mice in Spain (27 out of 29 tested) carry the gene version vkorc1 of the wild mouse and not of the house mouse. Even in Germany, where there is no wild mouse population, about a third of the mice (16 out of 50 tested) carried the wild mouse gene. The researchers tested the difference in the resistance of house mice with the wild mouse gene compared to house mice without this gene. The researchers saw that when mice with the wild mouse gene are exposed to warfarin, and even to stronger and more advanced anticoagulants, the mortality rates are 9-20% instead of 84-100% in "normal" house mice.

The wild mouse is resistant to warfarin even though it is almost never exposed to this poison. The wild mouse feeds mainly on seeds, which are poor in vitamin K. Song and her colleagues believe that the gene vkorc1, which, as mentioned, is involved in the activity of this vitamin, changed during the evolution of the wild mouse and underwent adaptations that help to deal with vitamin deficiency. A wonderful side effect (for the mouse) of this match is increased resistance to rat poison. Indeed, other rodents that feed mainly on seeds, such as common spiny and golden hamster, are also resistant to anticoagulants.

But how did the resistance gene get from the wild mouse to the house mouse? The two mouse species split between 1.5 and 3 million years ago and lived in different parts of the world. However, with the spread of man in the world and house mice in his wake, mouse populations met in parts of Europe and Africa, and in rare cases even mated and produced hybrid offspring. Crossing between different species to obtain a hybrid (hybridization) is a well-known phenomenon in the evolution of plants and contributed, for example, to the development of cultivated wheat. But nevertheless, in the case of animals, hybrids often have no future. For example, the hybrid mule is created by mating a mare and a donkey and is almost always infertile. Like the mule, the products of the mating between the two mouse species are sterile, though not all. Among the hybrids some of the females and all the males are sterile. On top of that, hybrid mice suffer from various physical problems that make it difficult for them to survive in the wild.

Although some of the daughters of the hybrids are fertile, and no doubt appeared over the years after the house mouse and the wild mouse met, the gene for resistance was transferred to the house mouse and spread in the population only 5 to 22 years ago. With the increase in the use of warfarin and similar poisons, the hybrids had a huge advantage that compensated for all their shortcomings - they did not die from the poisons. As a result, the fertile hybrid girls survived and could mate with house mice and pass the gene for resistance to the offspring. The offspring also bred with house mice and thus through a process of natural selection lost most of the foreign DNA, which did not benefit them or even harmed them, and kept the gene for resistance.

The researchers showed in the study that even in animals, and not only in plants and bacteria, there is more than one way to increase the variation in genes and develop new adaptations - the familiar way of mutations appearing or a rarer way of receiving genes from a related species. They also emphasized that humans are responsible for the special relationship created between the mice: the spread of man and with him the house mouse enabled the meeting between the different species of mice. At a later stage, man's use of rat poison created a selection pressure that gave an advantage to hybrid offspring of the mice and caused the spread of immunity to the poison in the population, as it is said: "What doesn't kill, forges."

The original article:

Song, Y. et al. Adaptive introgression of anticoagulant rodent poison resistance by hybridization between Old World mice. Current Biology 21, 1296-1301 (2011). doi: 10.1016 / j.cub.2011.06.043

The original article was published in Galileo magazine issue 157