Borrowed Resistance: How House Mice Acquired Rodenticide Resistance from Another Species

1. Introduction: resistance that did not have to evolve

Resistance management rests on an unstated assumption: that a population must wait for a resistance allele to arise, and then for selection to raise it. Rotation, mixtures and dose strategies all try to slow the second step.

1.1 Three routes

A resistance allele can arise by new mutation, can already be present as rare standing variation, or can arrive by gene flow from another population or species. Our anticoagulant treadmill article noted that rat resistance alleles appear to have segregated in the ancestral environment rather than arising by new mutation under selection. This article takes the third route.

1.2 What it argues

That borrowing collapses the waiting time resistance management relies on; that in house mice it has happened, spread widely and persisted; and that the same mechanism has moved insecticide resistance between malaria mosquito species. Sections 22 to 24 are the case.

1.3 Why a pest control reader should care

When bait stops working, the usual explanations are bait aversion, which our rodent behaviour article examined, reinvasion from a neighbouring source, or resistance. Where resistance is the cause, this article is about where it can come from, and why it can arrive faster than stewardship assumes.

That framing is ours.

2. The target

One enzyme.

Anticoagulant rodenticides specifically inhibit the VKORC1 enzyme essential for recycling vitamin K, preventing blood clotting and causing death by haemorrhage. Numerous mutations of the Vkorc1 gene have been reported in rodents, and some lead to resistance.³

2.1 A single target is a single point of failure

Every anticoagulant, first or second generation, acts on the same enzyme, so any change in it that reduces binding is relevant to the whole class.

That framing is ours; the treadmill article develops it.

2.2 Resistance appeared quickly

Resistance was first detected in brown rats in 1958 and in house mice in the early 1960s in the United Kingdom, within a decade or so of the first anticoagulants.⁵

2.3 Which is fast for a new mutation

A speed that invites the question of where the alleles came from, which is the question our treadmill article and this one address from different directions.

That framing is ours.

3. Two species of mouse

Neighbours that occasionally interbreed.

The western European house mouse and the Algerian mouse are described as sympatric, living in the same areas, and a study of Barcelona's mice notes that individuals carrying the introgressed variants have been found in rural Spain.⁶

3.1 They are distinct species

Hybridisation between them carries costs: the Barcelona authors note the sterility of first-generation hybrid males and partial genetic incompatibilities between the two genomes.⁶

4. The finding

Published in 2011.

Researchers reported a polymorphic introgressed genomic region in European house mice that stems from the Algerian mouse, spans more than 10 megabases on chromosome 7, and includes Vkorc1, the molecular target of anticoagulants.¹

4.1 From a sample of Western European mice

The study sequenced the transcribed Vkorc1 of 106 Western European house mice and identified 20 genotypes, aligning them to the Algerian mouse's gene.²

4.2 A commentary named it

A commentary accompanying the paper was titled "Adaptive introgression: the seeds of resistance".¹

5. The segment

A data note.

The original abstract describes the introgressed region as spanning more than 10 megabases.¹ The Barcelona paper describes the same study as identifying a 20-megabase segment.⁶

5.1 Both can be true

"More than 10" includes 20, and the introgression is described as polymorphic, with complete, partial and recombinant forms,² so segment length may vary between mice. We report both rather than choosing.

5.2 Why the size matters

A segment of that length carries many genes besides Vkorc1, which is relevant to §24.

That inference is ours.

5.3 Why a data note belongs here

A figure that changes from "more than 10" to "20" between an original paper and a later citation is the kind of drift this journal has tracked before, and it is harmless only because both figures are compatible. We record it so that a reader checking either source finds what we found.

6. Proof in the laboratory

Not only a correlation.

The authors showed that in the laboratory the homozygous complete Vkorc1 allele of the Algerian mouse confers resistance when introgressed into the house mouse.¹

6.1 Characterised further

A later French study assessed the consequences of the introgression through the in vivo resistant phenotype of introgressed mice, the ex vivo resistance of liver VKOR activity, and a recombinant version of the Algerian protein expressed in yeast.³

6.2 Three levels of evidence

A living animal's response, the enzyme's behaviour in liver tissue, and the isolated protein's behaviour in yeast together tie the resistance to the gene rather than to anything else the mice might carry.

That assessment of the design is ours.

7. Evolved before the poison

The most striking detail.

The 2011 study detected adaptive protein evolution of Vkorc1 in the Algerian mouse itself, with radical amino acid substitutions that apparently cause anticoagulant tolerance in that species as a pleiotropic effect.¹

7.1 Tolerance as a by-product

Positive selection produced an adaptive, divergent allele in the donor species for some other reason, and that allele happened to resist anticoagulants.¹

7.2 So the resistance predates the product

The allele that defeats warfarin in house mice existed in another species before warfarin was synthesised. No amount of careful product stewardship could have prevented its existence.

That consequence is our reading.

7.3 How the authors detected it

They report a ratio of non-synonymous to synonymous change in the donor's Vkorc1 of 1.54 to 1.93.¹ By the standard reading of that measure, a ratio above one indicates that changes to the protein were favoured rather than merely tolerated.

The interpretation of the ratio is the conventional one, not a claim specific to this paper.

8. Crossing a barrier

The study describes the allele as having crossed a species barrier to produce an adaptive polymorphic trait in the recipient species.¹

8.1 The process

The authors use the term for a naturally occurring sequence of interspecific mating followed by generations of backcrossing, and selection on introgressed alleles if they become advantageous.²

8.2 Despite the cost of hybridising

The introgression has a selective advantage, the Barcelona authors write, because carriers survive rodenticide exposure better, despite first-generation male sterility and partial incompatibility.⁶

8.3 A narrow gate

If first-generation hybrid males are sterile, the segment has to pass through hybrid females and then backcrossing, which makes each crossing rare. Selection after exposure is what turned a rare crossing into a common genotype.

That reasoning is ours, from the sterility the Barcelona authors describe.

9. A neutral passenger

Until the environment changed.

The authors note that changes in ecological settings, such as sudden rodenticide exposure, can render introgressed alleles that were effectively neutral adaptive.²

9.1 Borrowed alleles can wait

An allele carried at low frequency without cost or benefit is exactly the standing variation our treadmill article described. Borrowing is a way of stocking that shelf in advance.

That connection is ours.

9.2 The Barcelona authors say the same

They describe their city's case as widespread resistance due to selection acting on standing variation, in this case an introgression.⁶

9.3 Why neutral before the poison

Without anticoagulants in the environment, a version of VKORC1 that resists them gives no advantage, so nothing drives it up; if it costs little, nothing drives it out either. That is the condition under which a borrowed allele can persist at low frequency for a long time.

That reasoning is ours, following the authors' point about neutral passengers.

10. The sweep

After the 1950s.

The study found signatures of selection in patterns of variation in house mice consistent with selection on the introgressed allele after the introduction of rodenticides in the 1950s.¹

10.1 One estimate of timing

One bootstrapped estimate placed the selective sweep 25 to 36 generations, or 5 to 11 years, before the study, which the authors describe as consistent with a recent sweep when rodenticides were already in use.²

10.2 With the caveat they give

They add that broader sampling would be needed to clarify whether the introgression has multiple origins and to describe its timing and spread.²

10.3 Recent relative to the first poisons

An estimate of 5 to 11 years before 2011 places the sweep decades after warfarin came into use, which suggests the allele's spread may have tracked later changes in use rather than the first exposure.

That inference is ours and rests on a single estimate the authors themselves qualify.

11. Four amino acids

The mechanism in the protein.

The adaptive introgression causes the substitution of four amino acids in the house mouse protein.³

11.1 Identified as the cause in the field

The French authors concluded that the four introgressed polymorphisms were clearly the cause of the strong resistant phenotype observed in the field.⁴

11.2 A package, not a point mutation

Four substitutions arriving together is different from the single changes the rat literature usually describes, which matters for how resistance is tested (§23).

That distinction is ours.

12. How far it has travelled

Beyond the donor's range.

The French authors wrote that the introgressed polymorphisms may explain the widespread distribution of the genotype from Spain to Germany.⁴ A 2023 study lists detections in northern Spain, France, Switzerland and Germany, far beyond the geographic range of the donor species.⁷

12.1 Carried by the recipient

Once in house mice, the allele travels wherever house mice do, which is wherever people go.

That is our inference.

12.2 And on islands

The Italian islands survey is titled as revealing widespread rodenticide resistance in house mice across eleven islands.⁹

12.3 Islands are where eradication depends on poison

Our gene drive article described islands as the setting where rodent eradication is most valuable. Resistance there turns a finite eradication into an escalating one.

That connection is ours.

12.4 Why distance does not protect

The donor species' range sets where the allele can be acquired. Commerce in goods that carry mice sets where it can go afterwards, and the two are unrelated.

That point is ours.

13. Barcelona

Researchers sequenced exons 1, 2 and 3 of Vkorc1 from 111 house mice captured across the city and found SNPs associated with resistance to first- and second-generation anticoagulants in all of them. Of the individuals analysed, 94.59 % carried mutations associated to introgression events with the Algerian mouse.⁶

13.1 Mostly bromadiolone resistance

Most of the SNPs were associated with resistance to bromadiolone, though some were associated with resistance to brodifacoum.⁶

13.2 What "all of them" means

The mice were captured across the city, and every one sequenced carried at least one resistance-associated variant.⁶ That is a description of the sample, not proof that no susceptible mouse exists in Barcelona, but it leaves little room for one.

The qualification is ours.

14. Persistence after use declined

A reversion that did not happen.

The Barcelona results were similar to those for mice sampled in 1991 in rural areas, even though the city's public health agency had greatly reduced bromadiolone use over the years. The authors attribute persistence to many years of high bromadiolone use in the home, both domestic and professional.⁶

14.1 Reducing professional use was not enough

If householders continue to use the same compound, the selection pressure continues, whatever the public agency does.

That reading is ours, from the authors' reference to domestic use.

14.2 Against our reversion article

Our article on resistance reversion found that susceptibility sometimes returns when a chemistry is withdrawn. Barcelona is a case where partial withdrawal left resistance near fixation.

14.3 Domestic use as a selection source

The authors attribute persistence to high bromadiolone use for mouse control in the home, whether domestic or professional.⁶ A public agency can change its own purchasing; it cannot change what households buy.

The second sentence is ours.

15. Second-generation compounds

The escalation that was meant to answer resistance.

The Barcelona study found a mutation, Leu128Ser, at low frequency, which confers resistance to brodifacoum, and cites work showing that the combination of Ala26Ser and Leu128Ser also leads to brodifacoum resistance.⁶

15.1 The treadmill's history

Resistance to first-generation compounds led to the development of second-generation molecules such as bromadiolone, difenacoum, flocoumafen, brodifacoum and difethialone in the 1970s and 1980s.⁵

15.2 An imported allele meeting a local one

The introgressed package plus a locally occurring substitution is a route to resistance against a compound that neither alone might defeat.

That possibility is our inference from the cited combination.

15.3 Low frequency today

A variant that is rare in an unselected population is exactly the standing variation that brodifacoum use would favour. The Barcelona result gives no reason to think brodifacoum resistance is common there now; it gives a reason to watch.

That reading is ours.

16. Where it is absent

A useful contrast.

A study of house mouse populations in Western Australia detected no resistance-related Vkorc1 mutations in either population sampled.⁸

16.1 Absence is also information

Populations far from the donor species and from its introgression zone need not carry the allele, which is why local testing matters rather than assuming a global pattern.

That is our reading.

16.2 Biosecurity as resistance management

The Western Australian study's title frames its result as having implications for conservation and biosecurity.⁸ Keeping resistant mice from arriving is a form of resistance management that rotation cannot offer.

The second sentence is ours.

16.3 Isolation as the protective factor

Western Australia is separated from the donor species by geography and from European mouse populations by distance and quarantine. If introgressed alleles travel with mice, the places least likely to receive them are those that receive the fewest mice, which is the same logic our gene drive article applied to islands, running in the opposite direction.

That reading is ours; the Australian study, as we read its abstract, reports the absence of these mutations and does not attribute a cause.⁸

17. Why findings differ

The Barcelona authors note that some studies report a low frequency of Vkorc1 mutations, 3.3 per cent in one, while others find resistance-associated variants above 70 per cent, and suggest the differences are probably largely caused by differences in rodent management and the anticoagulants used.⁶

17.1 And by history

They add that standing variation and the natural history and distribution of different mouse species can largely determine how populations respond.⁶

17.2 Resistance in islands, too

A survey of eleven Italian islands, where more than a hundred rodent eradications have been attempted with anticoagulants, reports that resistant individuals reduce management efficiency and lead to excessive use, increasing the risk to non-target species.⁹

17.3 Comparisons need the same method

A study that sequences whole exons and one that screens for two or three known mutations are not measuring the same thing, so a figure of 3.3 per cent and one of over 70 per cent may differ partly by method. Our article on reference strains made a similar point about the denominator in resistance ratios.

That caution is ours.

18. The mosquito parallel

During a recent period of hybridisation between two major African malaria mosquitoes, a genomic island of divergence on chromosome 2 introgressed from one species into the other and increased in frequency, coincident with the start of major insecticide-treated bed net campaigns in Mali.¹⁰

18.1 The authors' interpretation

They suggest that increased insecticide exposure acted as a selective force sufficient to drive introgression of an entire genomic island across the reproductive barrier separating the two species.¹⁰

18.2 Described as rare

The authors present their case as a rare example of adaptive introgression in an animal species, and as showing the temporal dynamics of how resistance evolved in the recipient.¹⁰

19. What moved, and when

A dated event.

The study reports that during a brief breakdown in assortative mating in 2006, one species inherited the other's entire divergence island, including a suite of insecticide resistance alleles. Three SNPs were absent in pre-2006 collections but present in post-2010 samples of both species.¹⁰

19.1 Bed net use rose from 2005

A related study describes a dramatic increase in bed net usage in Mali starting in 2005 as likely having altered the fitness landscape and promoted the introgression of kdr.¹²

19.2 With a casualty

Another study reports that a reproductively isolated insecticide-susceptible population was driven to local extinction, likely by strong selection from increased bed net use.¹¹

19.3 A package in mosquitoes too

The molecular ecology study reports that individuals carrying both kdr and a nearly fixed X-linked haplotype, encompassing at least four genes including a P450 detoxification gene and a cuticular protein gene, rapidly increased in relative frequency.¹¹

19.4 Which links three of this journal's mechanisms

Target-site change, metabolic detoxification and cuticular penetration, the subjects of our synergist and cuticular resistance articles, appear together in one borrowed combination.

That connection is ours.

19.5 And the recipient became the main vector

A further study reports that the recipient species increased in relative abundance coincident with the 2006 introgression and is now the major malaria vector in southern Mali, and that kdr has been increasing in distribution and frequency across Africa, apparently in response to bed net use.¹⁴

20. A barrier that closed again

The genes stayed.

Early-stage hybrids between the two mosquitoes are typically short-lived, presumably because of reduced fitness, but cases where hybrids overcame that bottleneck and backcrossed have been reported in Guinea-Bissau, Ghana and Mali, and reproductive isolation was quickly re-established.¹²

20.1 A brief window is enough

The species stayed distinct; only the useful block of genes crossed. A barrier does not need to fail for long to let an adaptation through.

That reading is ours.

20.2 Frequencies levelled

A further study notes that knockdown resistance mutations were initially far more common in one species than the other even where they live together, and that recent adaptive introgression has since levelled the frequencies.¹³

20.3 The window coincided with the pressure

The breakdown in mating barriers the mosquito study dates to 2006 fell one year after bed net use began rising sharply, so the brief opening in the barrier occurred just as the selective reason to keep what came through appeared.¹⁰¹²

The juxtaposition is ours; the authors describe the introgression as coincident with the campaign.

21. How common this is

Rarer in animals, but documented.

Adaptive introgression is thought to be most common in plants, but clear animal examples include warfarin resistance in mice, coat colour in wolves, wing patterns in butterflies and insecticide resistance in African malaria mosquitoes.¹¹

21.1 Two of those four are pest control

Of the animal examples usually cited, half concern resistance to the products this trade and public health programmes use.

That observation is ours.

21.2 And a mechanism for rapid change

The mosquito authors describe the process as a mechanism for the rapid evolution of insecticide resistance.¹⁰

21.3 The deliberate counterpart

Our gene drive article described engineering an allele to spread through a population that did not produce it. Introgression is the unplanned version: an allele from outside spreading because selection favours it. Both show that where a gene came from matters less than what the environment rewards.

That comparison is ours.

22. What borrowing removes

Our argument.

Resistance management buys time by slowing selection on alleles that are rare or not yet present. Introgression delivers a finished, tested allele from a population where it was already common, so the waiting time for its origin is zero.

22.1 And the donor has done the testing

An allele that has been under selection in another species for a long time arrives without the costs a fresh mutation often carries, since selection in the donor has already shaped it.

22.2 Relatives become reservoirs

A closely related species that shares a target gene is a potential source of resistance to any product aimed at that gene, even if the relative has never been exposed to the product.

Sections 22 to 22.2 are our reasoning, from §§7 and 9.

22.3 What we did not find

Whether comparable borrowing has moved resistance between rat species we did not establish; the documented rodent case is the house mouse.

22.4 And for any new product

A product with a new target is durable only as long as no relative carries a tolerant version of that target. Nobody can survey every relative in advance, so claims that a new mode of action will not meet resistance rest partly on ignorance of what relatives carry.

That caution is ours.

23. What monitoring should look for

Also ours.

A diagnostic that tests for a handful of known single mutations may miss a multi-substitution introgressed package, or may classify it correctly only if the package's markers are on the panel. The Barcelona study sequenced whole exons, which is what allowed the introgressed variants to be recognised.⁶

23.1 Our diagnostics article

Our article on pooled genotyping argued that the barrier to resistance testing is organisational rather than technical. Introgression adds a design requirement: the method has to be able to see haplotypes, not only points.

23.2 And bioassays still matter

A feeding test measures the phenotype whatever its genetic source, which is why it remains the check on any genotype panel.

23.3 A panel built for rats may undercount mice

Our secondary poisoning article reported a national survey detecting two house mouse mutations and one new one. A survey designed around known point mutations answers the question it asks, and the introgressed package is a different question.

That caution is ours.

24. What it means for rotation and reversion

Our reasoning.

Rotation and reversion both depend on resistance carrying a cost when the selecting chemistry is absent. A segment of many megabases from another species carries other genes whose effects in the recipient are unknown in both directions.

24.1 So costs cannot be assumed

Barcelona's persistence after reduced bromadiolone use is at least consistent with a borrowed package carrying little cost in the conditions there.⁶

24.2 Nor can the direction of linked effects

Linked genes might as easily help as harm the carrier, which is a question for research rather than an assumption for management.

24.3 Rotation within the class does not escape the target

Every anticoagulant acts on VKORC1, so rotating between them changes potency but not the target; and a citing study reports that mice with the Algerian genotype have been observed to be resistant to different kinds of anticoagulant.⁹ Moving outside the class means moving to compounds our bromethalin article described as carrying their own costs.

The first and last sentences are ours.

24.4 What would change our view

Evidence that introgressed carriers decline when anticoagulant use stops entirely would show the package carries a cost, and would make withdrawal a useful tool again. Barcelona reduced use but did not stop it, so it cannot answer the question.⁶

That reasoning is ours.

25. A note on sources

Who did the work.

One of the French studies lists an author affiliated with a rodenticide manufacturer.⁵ Industry involvement in resistance research is common and useful, and we note it as we would for any commercial interest.

25.1 The core finding is independent

The 2011 study's first author was based in a university department of ecology and evolutionary biology.¹

25.2 Why industry funds this work

Resistance threatens a manufacturer's products, so manufacturers have reason to study it. That aligns their interest with accurate measurement of resistance, but not necessarily with conclusions about alternatives to their products, which is why independent replication matters.

That observation is ours.

26. What we take from it

Three things.

Resistance can be imported, not only evolved. Sections 4 to 12.¹

Once imported, it can persist when use falls. Section 14.⁶

And monitoring has to be designed for packages. Section 23, which is our argument.

And the mosquito case shows it is not unique to mice. Sections 18 to 20.¹⁰¹²

27. Our own position

The disclosure.

This company sells rodent control, and the resistance described here bears on how well the products the trade uses work. We make no claim here about any particular product we use or about resistance in the mice we treat.

28. The Manitoba position

28.1 Resistance in mice has been reported in Canada

A 2017 review lists Canada among the countries where anticoagulant resistance has been reported.⁵

28.2 Vkorc1 status here is unmeasured

Our diagnostics article recorded that rodent Vkorc1 genotype has not been measured in Manitoba, and we found nothing since that changes that.

28.3 So the introgressed package is an open question

We found no North American data on the introgressed allele. Whether it has reached Canadian house mice is unknown to us, and the way to find out is the sequencing §23 describes.

28.4 What a local test would look like

Whole-exon sequencing of Vkorc1 in a sample of trapped mice, as in Barcelona, together with a feeding test of the same population, would answer both the genetic and the practical question.⁶

That proposal is ours.

29. Limitations and open questions

We read abstracts and extracts. The mouse findings reach us through abstracts, a full-text extract of the 2011 paper and citing studies, and the mosquito findings through abstracts and reviews.¹²¹⁰

The segment size is reported two ways. We give both (§5).¹⁶

The timing estimate is one of several. The sweep date we report is one bootstrapped estimate, and the authors call for broader sampling.²

One island source is mixed. The Italian islands survey reaches us through a research-sharing page for a different paper.⁹

Nothing here is local. Every population studied is in Europe, Australia or Africa.

We did not read the commentary. The title of the commentary accompanying the 2011 paper is cited from the paper's record; we did not read its argument.¹

Industry involvement is noted, not assessed. One French study has a manufacturer-affiliated author; we have no reason to doubt its findings and no basis to assess them independently.⁵

Sections 1.3, 2.1, 2.3, 5.2, 5.3, 6.2, 7.2, 8.3, 9.1, 9.3, 10.3, 11.2, 12.1, 12.3, 12.4, 13.2, 14.1, 14.3, 15.2, 15.3, 16.1, 16.2, 16.3, 17.3, 19.4, 20.1, 20.3, 21.1, 21.3, 22 to 25 and 28.3 to 28.4 are our reasoning. The argument about waiting time, the implications for monitoring, rotation and reversion, and the Manitoba application are ours rather than sourced positions.

30. Conclusion

European house mice did not have to evolve resistance to anticoagulants from scratch. A version of the Vkorc1 gene, shaped by selection in the Algerian mouse for reasons unrelated to poison, crossed into house mice through hybridisation despite sterile first-generation males, waited as a passenger, and swept after rodenticides arrived in the 1950s.¹⁶ Four introgressed amino acid substitutions have been identified as the cause of a strong resistant phenotype found from Spain to Germany, far beyond the donor's range.⁴⁷ In Barcelona every one of 111 mice carried resistance-associated variants and nearly 95 per cent carried the introgressed ones, a picture unchanged since 1991 despite reduced public use of bromadiolone.⁶

Malaria mosquitoes in Mali did the same with insecticide resistance: a brief breakdown in mating barriers in 2006, coincident with a bed net campaign, moved a block of resistance genes from one species into another, after which the barrier closed and the genes stayed.¹⁰¹²

Resistance management assumes time: time for an allele to arise and time for selection to raise it. Borrowing removes the first entirely. The practical consequences are that a related species can be a reservoir of resistance to a product it has never met, that monitoring has to be able to see multi-gene packages rather than single points, and that the costs rotation and reversion depend on cannot be assumed for a segment of another species' genome. Whether the package has reached mice in Manitoba is unmeasured.

References

1. Adaptive introgression of anticoagulant rodent poison resistance by hybridization between Old World mice, published in a biology journal in 2011 by authors including a university department of ecology and evolutionary biology, read as its abstract. Peer-reviewed material. Source for the finding that resistant house mice can originate from selection on Vkorc1 polymorphisms acquired from the Algerian mouse through introgressive hybridisation; the introgressed region spanning more than 10 megabases on chromosome 7 and including Vkorc1; the laboratory demonstration that the homozygous complete Algerian allele confers resistance when introgressed into house mice; signatures of selection consistent with selection after the introduction of rodenticides in the 1950s; adaptive protein evolution of Vkorc1 in the Algerian mouse with radical amino acid substitutions apparently causing anticoagulant tolerance as a pleiotropic effect; the allele crossing a species barrier to produce an adaptive polymorphic trait; and the title of the accompanying commentary, Adaptive introgression: the seeds of resistance. https://pubmed.ncbi.nlm.nih.gov/21782438/
2. The same 2011 paper, read as an extract of its full text on the publisher's site. Peer-reviewed material. Source for the sequencing of 106 Western European house mice identifying 20 Vkorc1 genotypes; the definition of the process as interspecific mating followed by generations of backcrossing and selection on introgressed alleles; the statement that changes in ecological settings such as sudden rodenticide exposure can render effectively neutral introgressed alleles adaptive; a bootstrapped estimate of the selective sweep at 25 to 36 generations or 5 to 11 years before the study, consistent with a recent sweep during rodenticide use; the description of complete, partial and recombinant introgressed forms; and the authors' call for broader sampling to clarify multiple origins, timing and spread. https://www.cell.com/current-biology/fulltext/S0960-9822(11)00716-0
3. Study of the efficiency of anticoagulant rodenticides to control house mice introgressed with Algerian mouse Vkorc1, published in a pest management journal in 2017 and read as its abstract. Peer-reviewed material. Source for the description of anticoagulants as specifically inhibiting the VKORC1 enzyme and causing death by haemorrhage; the note that numerous Vkorc1 mutations have been reported in rodents, some leading to resistance; the statement that the introgression causes the substitution of four amino acids; and the study's methods of assessing in vivo phenotype, ex vivo liver VKOR activity and a recombinant protein expressed in yeast. https://pubmed.ncbi.nlm.nih.gov/27196872/
4. Bibliographic record of the 2011 paper on a scholarly search platform, displaying an extract from the 2017 French study's conclusions. Abstract extract, flagged as read second-hand. Source for the conclusion that the four introgressed polymorphisms were clearly the cause of the strong resistant phenotype observed in the field and may explain the genotype's widespread distribution from Spain to Germany. https://www.semanticscholar.org/paper/Adaptive-Introgression-of-Anticoagulant-Rodent-by-Song-Endepols/f658f4653a3cbc43ab5330fb7cd50dd01d3e1162
5. Adaptative evolution of the Vkorc1 gene in house mice is influenced by the selective pressure of anticoagulant rodenticides, published in an ecology and evolution journal in 2017, with an author affiliated with a rodenticide manufacturer. Peer-reviewed material with an industry-affiliated author, flagged. Source for resistance being first detected in brown rats in 1958 and in house mice in the early 1960s in the United Kingdom and since reported in many countries including the United States, Canada, Japan and Australia; and for resistance to first-generation compounds leading to the development of second-generation molecules including bromadiolone, difenacoum, flocoumafen, brodifacoum and difethialone in the 1970s and 1980s. https://pmc.ncbi.nlm.nih.gov/articles/PMC5395456/
6. Widespread resistance to anticoagulant rodenticides in house mice in the city of Barcelona, published in an environmental science journal in 2022. Peer-reviewed material. Source for the sequencing of Vkorc1 exons 1 to 3 in 111 mice finding resistance-associated SNPs in all, 94.59 per cent carrying variants associated with introgression from the Algerian mouse, most associated with bromadiolone resistance and some with brodifacoum; results similar to rural mice sampled in 1991 despite the city public health agency greatly reducing bromadiolone use, attributed to many years of high domestic and professional use; the low-frequency Leu128Ser mutation conferring brodifacoum resistance and cited work on the Ala26Ser plus Leu128Ser combination; the description of the case as selection on standing variation, in this case an introgression; the description of the 2011 study as identifying a 20-megabase segment; first-generation hybrid male sterility and partial incompatibility; introgressed carriers found in rural Spain where the two species coexist; and the range of reported frequencies from 3.3 per cent to over 70 per cent, attributed largely to management and anticoagulant differences. https://www.sciencedirect.com/science/article/pii/S0048969722042905
7. Study of rodenticide resistance mutations among house mice in Portuguese Macaronesian islands and Iberian Atlantic areas, published in an environmental science journal in 2023 and read as an extract. Peer-reviewed material. Source for the statement that the introgressed allele has been detected in northern Spain, France, Switzerland and Germany, far beyond the geographic range of the donor species. https://www.sciencedirect.com/science/article/pii/S004896972304915X
8. Study of house mouse populations in Western Australia, published in 2020 and read as its abstract. Peer-reviewed material. Source for the finding that no resistance-related VKORC1 mutations were detected in either population sampled. https://pubmed.ncbi.nlm.nih.gov/32970676/
9. Abstract of a survey of VKORC1 mutations in house mice on eleven Italian islands, displayed on a research-sharing platform page for the 2011 paper. Abstract read second-hand, flagged. Source for the survey's title describing widespread rodenticide resistance in house mice across eleven Italian islands; more than one hundred rodent eradications attempted on Mediterranean islands with anticoagulants; the statement that resistant individuals reduce management efficiency, leading to excessive use and increased risk to non-target species; and a citing passage on the same page reporting that mice with the Algerian genotype have been observed to be resistant to different kinds of anticoagulant. https://www.researchgate.net/publication/51514765_Adaptive_Introgression_of_Anticoagulant_Rodent_Poison_Resistance_by_Hybridization_between_Old_World_Mice
10. Adaptive introgression in an African malaria mosquito coincident with the increased usage of insecticide-treated bed nets, published in a national academy journal in 2015 and read as its abstract. Peer-reviewed material. Source for the introgression of a chromosome 2 divergence island between two malaria mosquito species during a brief breakdown in assortative mating in 2006, including a suite of insecticide-resistance alleles, coincident with the start of a major bed net campaign in Mali; three SNPs absent in pre-2006 collections but present post-2010; the suggestion that insecticide exposure was a selective force sufficient to drive introgression across the reproductive barrier; and the description of the process as a mechanism for rapid evolution of insecticide resistance. https://pubmed.ncbi.nlm.nih.gov/25561525/
11. Study of complex genome evolution in one of the same malaria mosquito species, published in a molecular ecology journal and read through a public biomedical archive. Peer-reviewed material. Source for the statement that adaptive introgression is thought to be most common in plants, with clear animal examples including warfarin resistance in mice, coat colour in wolves, butterfly wing patterns and insecticide resistance in malaria mosquitoes; and for the report that a reproductively isolated insecticide-susceptible population was driven to local extinction, likely by selection from increased bed net use. https://pmc.ncbi.nlm.nih.gov/articles/PMC4615556/
12. The same molecular ecology study as published by the journal, read as an extract. Peer-reviewed material. Source for early-stage hybrids being typically short-lived, presumably due to reduced fitness; hybrids overcoming that bottleneck and backcrossing in Guinea-Bissau, Ghana and Mali; the dramatic increase in bed net usage in Mali from 2005 likely altering the fitness landscape and promoting introgression of kdr; and reproductive isolation being quickly re-established. https://onlinelibrary.wiley.com/doi/10.1111/mec.13382
13. Study of introgression at the range limit of a malaria mosquito, published in a general science journal in 2017. Peer-reviewed material. Source for the statement that knockdown resistance mutations were initially found at much higher frequency in one species than its sister species even where they are sympatric, and that recent adaptive introgression has since levelled the frequencies. https://www.nature.com/articles/srep46451
14. Study of genetic variation associated with increased insecticide resistance in a malaria mosquito, read through a public biomedical archive. Peer-reviewed material. Source for the statement that the recipient species increased in relative abundance coincident with the adaptive introgression of kdr in 2006 and is now the major malaria vector in southern Mali, and that kdr has been increasing in geographical distribution and relative frequency across Africa, apparently in response to increased bed net use. https://pmc.ncbi.nlm.nih.gov/articles/PMC5885317/