“Adaptive” hybridization in mice

July 22, 2011 • 5:30 am

One of the newer “expansions” of the modern synthetic theory of evolution is the idea that the genetic variation “used” by either natural selection or genetic drift can arise not just through mutations within a species, but also through hybridization with another species.  Hybridization between different species usually yields maladaptive offspring, but occasionally a fertile hybrid can be the source of a new gene that can spread through a species that didn’t originally have it.  (I’ve previously written about work showing that an adaptive color gene in aphids was acquired not by hybridization, but by ingestion.)

Such a case of “adaptive introgression” (“introgression is simply the acquisition of genes by one species or population from another by interbreeding) was just reported in Current Biology (reference below), and you can read a summary of the results in a piece by Kai Kupferschmidt in Science NOW (I’m quoted).

As reported by Song et al., the house mouse, Mus musculus domesticus, acquired a gene for rodenticide resistance by mating with a close relative, the wild mouse Mus spretus.  The rodenticide is the famous poison Warfarin, which is used widely to kill mice and rats.  It works by inhibiting the synthesis of blood clotting factors that themselves are dependent on vitamin K.  The mice then bleed to death internally. Warfarin is also used to inhibit the formation of blood clots in humans, but is called “Coumadin” for medical uses.  Since its introduction in the 1950s, many populations of mice have become resistant to the poison: this is a classic case of natural selection that isn’t as widely known as examples of bacterial resistance to antibiotics.

The poison.

Song et. al.  found through DNA sequencing that populations of the house mouse in Spain and Germany had one region of their genome, on chromosome 7, that actually came from Mus spretus. (The two species were formerly “allopatric”, i.e., lived in different places, until they become geographically contiguous when the house mouse moved with its human host.)  This region includes genes for Warfarin resistance, and experiments showed that house mice containing the introgressed spretus region lowered mortality from Warfarin and a similar poison from 84-100% to 9-20%.  The amino-acid sequence of the introgressed gene (vkorc1spr ) differed between the two species.  The authors haven’t done the definitive experiment—actually putting the spretus version of the gene into a house mouse genome and seeing whether it alone confers resistance to poison—but the mortality rates of introgressed house mus versus those lacking the gene are pretty good evidence.

Finally, the authors showed by population-genetic analysis that the spretus gene entered the house mouse population between 61 and 71 mouse generations ago, which corresponds to about 13-22 years in the wild, so the adaptive introgression occurred well after the poision was introduced. This again supports the notion that the spread of the spretus gene in house mice was promoted by natural selection for resistance to poison.

There are two questions to ask about this situation:

1. How common is adaptive introgression?  My guess (which you can see in the ScienceNOW link above), is probably that it isn’t very common.  Why? Because if it were, we would see it using DNA-based phylogenies.  Adaptive introgression would show up as a region of the genome that was much more similar to a region in a related species than could have occurred by simply genetic drift or natural selection in the first species.  We don’t see that kind of similarity very often. (It also could have other causes, like a variant in the common ancestor of the two species that simply was inherited by its descendants.)  So I suspect that while the capture of adaptive genes by hybridization occurs occasionally, it won’t be an important source of variation compared to mutation.

Further, most species (we are one) simply can’t form fertile hybrids with a related species, a condition that is necessary for adaptive introgression to occur. The genus Drosophila (the flies on which I work) contains about 1500 described species, but hybrids are known in only about a dozen cases, and most of these hybrids are sterile.

2.  Can species be selected to hybridize with other species?  Some biologists—especially botanists—have theorized that natural selection will foster those traits that facilitate one species mating with another one, so that it can capture alleles to facilitate its own evolution.  That doesn’t wash, because in the vast majority of cases the hybrids between different species are less fit than the parental species: hybrids can be sterile or inviable (the spretus/domesticus hybrids, for example, are largely sterile).  So, although hybridization may occasionally capture a “good” gene, most of the time it produces maladapted hybrid offspring.  Natural selection, then, would act to prevent rather than facilitate hybridization, because the beneficial effects of mating between species are far outweighed by the bad ones.

As the famous evolutionist Ronald Fisher wrote in 1930:

The grossest blunder in sexual preference, which we can conceive of an animal making, would be to mate with a species different from its own and with which hybrids are either infertile or, through the mixture of instincts and other attributes appropriate to different courses of life, at so serious a disadvantage as to leave no descendants. … it is no conjecture that a discriminative mechanism exists, variations in which will be capable of giving rise to a similar discrimination within its own species, should such a discrimination become at any time advantageous.

Mus spretus. Wild mice are incredibly cute, and I could never bring myself to kill them in traps.


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

33 thoughts on ““Adaptive” hybridization in mice

  1. I can think of one example where selection may be promoting hybridization, unidirectional hybrid mating between the Mexican and Plains spadefoot toads. Hybrids in both directions suffer from sterility ,though incomplete. However, in very ephemeral ponds where tadpoles only have a few weeks to develop and metamorphose, females of one species, The Plains spadefoot hybridize with Mexican spadefoot males fairly often, but the reverse is never seen. The explanation for this seems to be that Mexican spadefoot tadpoles develop more quickly, as do hybrids. So in short lasting ponds hybrid offspring have a better chance of leaving the ponds than pure Plains tadpoles, mitigating the cost of the (incomplete) sterility. -http://www.sciencemag.org/content/318/5852/965.abstract

  2. Minor note: You are referring to CoumaDin, not coumaRin. By itself, coumarin is a common secondary compound, but not an anti-coagulant. It is a precursor to dicoumarol (brand name Coumadin), which does have anticoagulant/rodenticide properties.

      1. One other minor note… the names “warfarin” and “Coumadin” are actually both used to refer to the drug given to humans. Warfarin is the generic name, Coumadin the brand name (like acetaminophen vs. Tylenol). People will usually call it Coumadin in verbal communication, but if you have any kind of electronic medical record, it should be listed as warfarin there.

        The Institute for Safe Medication Practices actually recommends writing it as warfarin (COUMADIN) with the brand in all caps in parentheses after the generic name, because of cases like the following, where a patient was taking both Coumadin and Jantoven without realizing that they’re actually the same drug:


        1. (W)isconsin (A)lumni (R)esearch (F)oundation

          Awesome. This stuff keeps me alive and I live like a mile from the place they invented it. I salute it everytime I go by.

  3. I love reading about studies like this.

    Thank you.

    This reminded me about speciation of homo species from homo sapiens into homo cogitans.

    It is hard to predict over how many generations the speciation will occur because it is hard to predict when and how the selective pressures of civilization collapse will play out. And it is hard to predict how mixed population of homo sapience and homo cogitans will survive the collapse of biosphere and struggle for survival of unimeginable scale.

    The science of human condition already exists but it is not institutionalized at all; it is ewven less institutionalized than evolution is institutionalize: we still have people individuals who claim to be “scientists” _and_ are proud to profess the “belief in god” by employing corresponding language.

    The breakdown of civilization due to overpopulation is already happening in parts of the world and institutionalization of science of human condition has begone as well.

    It would be interesting to see when a specific group within homo sapiens “separates”, organizes and moves into government witrh the view to implement “rapid population decline” globally

    That would mark the speciation from homo sapiens into homo cogitan.

    That would mark the end of diasporation of homo sapiens into whole-planet eco-niche.

    That would mark the beginning of the time of homo cogitans and their sustainable socio-economic system.

    1. When I was a kid I used to wish that I had been born in the future after scientists had solved the problems of aging, cancer, etc.

      Now that I’m an adult, I’m starting to think that this was one of the best generations to be born into.

      1. to be born sooner than later is best because those who will face the civilization collapse wil “curse” their fathers for doing so little to “stop beliefing in non-scientific non-sense”

        i am very happy i will be dead when the show progresses to its finale 🙂

    2. I love to read these articles too, but after that we have to disagree.

      “breakdown of civilization due to overpopulation is already happening in parts of the world”

      That is the exact opposite of what is seen. Earlier city civilizations had that problem on the global scale. Modern civilization has become more and more resilient towards this.

      On top of that overpopulation is projected to disappear, see for example Rosling’s data driven TED talks. The reason for that is the same; resilience is correlated with more and better managed resources, which translates to less poverty and fewer children.

      It is not rational to worry about what is not going to happen, and where we fully understand the mechanics of what is happening.

      Instead we could concentrate to become even better in minimizing environmental impact faster. We use up ~ 1/10 area for food production per person compared to those non-robust early societies that cut down the global woods thousands of year ago. (Apparently even vast parts of Amazon in newer satellite photos; that has regrown.)

      But that can be reduced much more. (Say, by synthetic biology production.) That seems to be the moral thing to do, since it helps the poorest most.

      As for your speciation model, I don’t think it bears up. Out of Africa populations could interbreed with other humans in at least two known cases. And they had been apart for hundreds of thousands of years. It is _very_ unlikely you could separate human populations over periods of millions of years. [But I am no biologist.]

      1. Overpopulation will not disappear before “belief-free science” becomes the shepherd of human condition

        Mankind as organism-whole is yet to understand its origins as warm blooded verterbrates and its deliberative capablity that put it on top of the food chain in the animal kingdom.

        The process that began with diasporation out of Africa is still going strong: we keep appropriating “genetic material” of the biosphere for our multiplication.

        Our survival as species is now only threatened by our lack of understanding the dynamics of closed planet system.

        Our socio-economic system reflects our primitive origins and depends on and promotes overpopulation. “Economy must grow” is paradigm that is fundamentally conjurational in nature and cannot be “validated” by science.

        You think science will discover how to convert our “wastes” and population will “stabilize” before collapse.

        Indeed population growth slows down but the consumption cannot slow down and resources will continue to be _irreversibly_ depleted until the system breaks down – the breakdown is manifesting itself already.

        You still have the luxury of “talking yourself” into “beliving in science solving all problems forever”.

        But your children will not have this option.

        And your grandchildren will ask a question:

        “What they where thinking doing what there doing? How could not they see where it was all going?”

    3. To be clear, overpopulation is a relative thing. Either you overgrow your current resource base, or it shrinks. The earlier city states seems generally to be suspected to have succumbed to prolonged (hundreds of years) local droughts, which made earlier perhaps stable population too large. Eventually the cities were then abandoned.

      1. Tobjorn,

        Overpopulation is indeed relative thing

        If you know simple math you will see that more people means less consumption per capita for all in the finite resources planet

        If you Google Jack Alpert and his idea of Rapid Population Decline (not going to work but it is another matter) he will take you thru calculation that to eradicate poverty and human conflict we need to decrese global population to 100 millions!

        Civilization will break down when poor will have nothing to eat because wealthy take another trip to the mall on the bio-fuel

        Current socio-economic system is unsustainable – you just don’t want to pay attention to the evidence. It is only a matter of time before the big bang and it is already happening quitely for people in Africa, Asia, Eastern Europe, Latin America – evrywhere in the world except North America. It will come there as well – you know Tea Party eventually taking to the streets.

        Overpopulation is indeed relative thing and we are in overshoot for quite a long time already.

  4. “I could never bring myself to kill them in traps”

    Well, then I think you’ve never had them pissing, shitting, and chewing in your home.

    I have NO PROBLEM killing them in traps. Instant death, the most humane way to take them out.

    Winter before last, some outdoor mice or voles ate the tubers/crowns/roots of $600 worth of perennials in our garden. Not last winter though! I made some PVC pipe mouse-hotels with blocks of D-Con …

  5. I didn’t even know the damned beasts could develop such resistance to coumadin. I agree the mice are very cute (even the house mouse) but they’re pests and I always stomp on them, poison them, or use nasty traps on them even though someone always complains about me being nasty. The only exception is when I’m in the fields – I just leave field mice alone.

  6. There is quite a long literature on adaptive introgression. We wrote a review of the concept in 2006 (open access PDF link):


    Adaptive introgression is highly evidenced in the recent molecular literature.

    This is not an “extended” aspect of the modern synthesis, in fact is was there from the start, pushed by G. Ledyard Stebbins and Edgar Anderson in the botanical literature. In my opinion, it is a real blind spot of zoologists that their view of the synthesis follows Mayr almost blindly and neglects the botanists who contributed from the start.

  7. Jerry Coyne

    Mus spretus. Wild mice are incredibly cute, and I could never bring myself to kill them in traps.

    This explains why all the kitty cats then.

  8. About 1998, I lived in a small basement suite in a house in Victoria, B.C. After a few months I noticed droppings in various places, and my landlord gave me a box of warfarin much like the one pictured above.

    The only effect I noticed was to change the colour of the droppings in my sock drawer from dark grey to light tan. “Sputnik” seems to have been thoroughly immune to the lethal effects. I don’t know the species, or the fertility of that individual (so named because I swore if I caught it I would launch it into space).

  9. In orchids, hybridization between species and even between genera are often fertile. The isolating mechanisms between species are usually physical (flower fragrance attracting one specific pollinator species, for example) rather than genetic, and natural hybrids do happen with some frequency. Orchids are the largest family of flowering plants, so this “grossest blunder” seems not to have diminished their success, and may well have helped them diversify.

  10. Well, there’s this complicated example from ants: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1691112/pdf/12350248.pdf

    The process of reproductive caste determination in eusocial insect colonies is generally understood to be
    mediated by environmental, rather than genetic factors. We present data demonstrating unexpected genetic
    differences between reproductive castes in a variant of the rough harvester ant, Pogonomyrmex rugosus
    var. fuscatus. Across multiple loci, queens were consistently more homozygous than expected, while workers
    were more heterozygous. Adult colony queens were divided into two highly divergent genetic groups,
    indicating the presence of two cryptic species, rather than a single population. The observed genetic
    differences between castes reflect differential representation of heterospecific and conspecific patrilines in
    these offspring groups. All workers were hybrids; by contrast, winged queens were nearly all pure-species.
    The complete lack of pure-species workers indicates a loss of worker potential in pure-species female
    offspring. Hybrids appear to be bipotential, but do not normally develop into reproductives because they
    are displaced by pure-species females in the reproductive pool. Genetic differences between reproductive
    castes are expected to be rare in non-hybridizing populations, but within hybrid zones they may be evolutionarily
    stable and thus much more likely to occur.
    Keywords: allozymes; caste determination; cryptic species; hybridization; kin selection

  11. I find it interesting that your views on hybridization and, by extension, evolution are framed using only animal models. The polyploid, hydridization, and speciation patterns exhibited by plants in many way refute much of what you’ve stated in your post (how many animal species increase and decrease the number of chromosomes in a cell over a few generations time?). It might be more correct for you to talk about the limited understanding animal biologists have about the topic of hybridization in organisms with closed developmental patterns.

    My frustration also extends to PZ Meyers over at his blog when he talks about developmental biology. He is, in reality, talking about animal development 100% of the time and rarely (never?) considers the patterns of protists, fungi, plants, cyanobacteria, etc. in his view of development. In the last decade university courses and textbooks have been renamed from “Animal Development” to “Developmental Biology” to be more “accurate” (at least in the minds of the faculty teaching the courses). A quick perusal of the syllabi and texts in question indicate they are extremely narrow in their focus with almost no discussion of any organisms than the usual animal models.

    Barbara McClintock once commented on this overall attitude using an example from the 1950s geneticists that stated that if you wanted to understand an elephant all you had to do was study a bacteria. The assumption was that the genetic principles guiding each were the same and the model bacteria was all you needed to know. I always loved her comment that “it didn’t turn out that way.”

    I’d like to see the end of evolutionary biologists making conclusions on gene regulation and population genetics as applying to all organisms when they in fact they don’t. Plants use hybridization and introgression as a matter of routine. In fact, a large percentage of plant species are thought to be products of these mechanisms.

    1. I don’t see how polyploidy in plants refutes anything I’ve said in the post above. Yes, there is polyploidy, which is a simple mechanical response to maladaptive hybridization: chromosome doubling restores fertility, but the chromosome number doesn’t double as an adaptive way to restore fertility! Allopolyploidy says nothing about whether plants are “adapted to hybridize.” Nor is there substantial evidence in plants that the adaptive introgression of genes from another species is far more common than in animals.

      And although you accuse me of ignorance about hybridization in plants, there is in fact an entire chapter on that topic, much of it about polyploidy, in the book I co-wrote with Allen Orr, Speciation.

      1. I took exception to the sentence in your post that read: “Hybridization between different species usually yields maladaptive offspring, but occasionally a fertile hybrid can be the source of a new gene…” I hold the position that allopolyploidy is a common mechanism in plant populations leading to well endowed offspring. It is a powerful source of genetic variation not a rare one producing maladapted offspring. If plants have such “plastic” genomes where mutations, hybridization events, and the appearance of B chromosomes lead to new species in as short as a single generation then it can be argued that the above mechanisms are highly adaptive.

        My point is that most of what is presented in posts/discussions on evolution is zoocentric and, often times, simplistic. It is a battle to get students (and the general public) to fully understand evolution when they get a one-size-fits-all presentation on the subject.

        Just call me a grumpy botanist that is tired of battling the perception that plants are boring (when in fact they do a lot more cool things than animals).

        1. First of all, polyploidy does not move genes from one species to another; it produces a nearly sterile hybrid which, if it undergoes genome doubling, can result in a new species. Polyploidy is a source of new species, not of genetic variation within species, which is what I was talking about with adaptive introgression. There are few biologists who would regard the origin of a new species as an adaptation. They can arise via adaptive changes in the genome.

          And, as I said, I have not ignored plants; if you read our book, Speciation, which you obviously haven’t, you’ll see that we use tons of plant examples, and have an entire chapter on polyploidy. The accusation that we’ve neglected plants is simply unfair.

          You can be grumpy on your own time, but don’t come over hear to accuse me of ignorance, or of neglecting plants. By all means address the scientific arguments, but it is, you know, possible to do that politely.

  12. There is a program on TV, “Billy, The Exterminator”. One of the programs was about a house “overrode” (a word from Albert the Alligator) with mice. There were also dogs in the house. The lady put out warfarin, without result. Billy explained to her that the mice were also eating dog food and getting enough vitamin K to render the warfarin ineffective.

    I take warfarin and my mice are under control.

  13. I suppose by wiping out the normal mates we actually encouraged the mice to select mates where they could, in this case with another (closely?) related species, as with wolf/dog/coyote hybrids.

  14. “I could never bring myself to kill them in traps”

    Me either. So I bought sticky traps and a large cage and, after trapping them, I let them live out their lives in the cage (with water, food, a treadmill, etc.)

  15. I do fish systematics and taxonomy. I have done hobby raising and breeding various succulents, cacti, and amaryllis. On reading the relevant plant taxonomic literature, I came to realize that plants and their characteristics are, in some aspects, quite different from most animals, and that botanists have their work cut out for them.

  16. Very interesting that there might have been gene transfer in so well developed organisms as mice. Good supporting evidence for the Idea that a few Neanderthal genes have made it into the European population.

    I am writing a Future History where a human population post civilization destroying asteroid impact has diverged into a diurnal species much like contemporary humans and a nocturnal species inspired by “The Island of the Colorblind” by Oliver Sacks. I had so far thought that most hybrids would be infertile or blind. Maybe there could be more gene transfer than I reckoned. BTW, the FH is set well over a hundred thousand years post impact, with only a few handfuls of humans surviving, so plenty of time for weird variations to arise.

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