Seven Generations, or Never: Whether Resistance Decays When You Stop Selecting For It

1. Introduction: the assumption nobody states

This journal has already examined insecticide rotation and found the evidence for it thinner than its status in the trade implies. This article goes underneath that, to the assumption rotation depends on.

1.1 Why that sentence matters

One species. One laboratory. Four chemistries. Three different answers to the question of how long resistance lasts after you stop using the product.

If there is no general decay rate, then rotating away from a chemistry for a fixed period is not a strategy. It is a hope with a calendar attached, and that framing is ours.

2. What a fitness cost means

The concept, stated plainly before the evidence.

A mutation that confers resistance frequently does so by degrading something the organism was using. An enzyme binds its target less well, a receptor changes shape, a detoxification pathway runs constantly at metabolic expense.

2.1 The consequence

In an environment without the insecticide, the resistant individual is worse at being an insect than the susceptible one. Over generations the susceptible type should recover the population.

That is the entire mechanical basis of every resistance management scheme that involves stopping and restarting a chemistry.

2.2 What costs look like when measured

Resistance costs are reported in association with reduced lifespan and oviposition rates; sometimes also longer maturation times.³ In one selected strain, relative fitness of the resistant line and of both reciprocal crosses was significantly less than that of the unselected strain.²

2.3 And how variable they are

Costs have a large variance ranging from nearly absent to very high costs.³ That variance is the subject of this article.

Where costs are nearly absent, fixation of the resistant variety is likely. Where they are very high, removal of the selective pressure might greatly decrease the frequency of the resistance associated alleles after some time.³

2.4 So the cost determines the strategy

Not whether resistance appears, which it will, but whether anything you do after it appears can undo it. A pest with cheap resistance is a pest whose lost chemistry stays lost.

That is a different question from the one resistance monitoring usually asks, which is how resistant a population currently is. This one asks whether the resistance is reversible, and that framing is ours.

3. The theoretical reason to expect one

Why the expectation is not merely wishful.

Following Wright's physiological theory of dominance, resistant alleles should be loss-of-function and thus recessive in pesticide-free environments, while sensitive alleles should become loss-of-function and thus recessive in pesticide-rich environments.⁹

3.1 Beneficial reversal of dominance

Studies across resistant insect populations suggest that resistant alleles of one target gene follow patterns of beneficial reversal of dominance often showing dominant benefits and/or recessive costs for fitness-associated traits, though direct evidence is lacking.⁹

3.2 The phrase to hold onto

Direct evidence is lacking.⁹ The theory is coherent and the measurements supporting its specific predictions are, by the authors' own account, not yet there.

4. The best-documented cost in the field

The rodent case, which is unusually clean because the mechanism is known at the level of a vitamin.

Anticoagulant resistance in Norway rats is primarily explained by selection on the mutations in the vitamin K epoxide reductase complex subunit 1 gene,⁷ and among variants with confirmed impact on resistance status mutations at position 139 of the gene are the most frequent.¹⁰

4.1 Resistance and the vitamin are the same thing

Resistance to warfarin and an increased vitamin K requirement appear to be pleiotropic effects of the same allele.⁵

This is as direct as a fitness cost gets. The altered enzyme is worse at recycling the vitamin, which is what makes the poison ineffective and what makes the animal hungrier for the vitamin.

4.2 The enzyme kinetics

In resistant rats carrying the position 139 variant, VKOR activity was lower and also less inhibited by warfarin than in susceptible rats, with both the maximum rate and the affinity constant lowered, so that the enzymatic efficiency of the VKOR was similar between resistant and susceptible rats.¹⁶

A slower enzyme that is harder to poison. The cost is not hypothetical and it is measurable.

5. Who actually pays it

The detail that complicates everything downstream.

In bromadiolone-resistant rats of a strain carrying a position 139 variant, under vitamin K deficiency blood clotting times increased in all homozygous resistant males within 8 days and in 80% of homozygous resistant females within 15 days. There was little effect on blood clotting in heterozygous males and no effect in heterozygous females.⁶

5.1 The heterozygote carries the allele and avoids the bill

Which is the single most important fact in this article. If carrying one copy confers useful resistance at little cost, the allele can sit in a population indefinitely without selection against it doing much work.

That is the recessive cost half of the dominance prediction in §3, observed directly.⁹⁶

5.2 And it requires a deficiency to appear at all

The cost was measured under vitamin K deficiency.⁶ A commensal rat living in a building with food waste may not experience that deficiency, in which case the cost does not express.

Costs are described elsewhere as context-dependent,¹¹ and this is what context-dependent means in practice. Our reading is that a cost which only appears under nutritional stress is a weak lever in an urban environment, which is exactly where we work.

6. The wild population that reverted

The case for the optimistic view, and it is a good one.

A large polymorphic population of rats was extensively poisoned with warfarin and the level of resistance monitored regularly for a period of 18 months after withdrawal of the poison. During this period the proportion of resistant animals in live-capture samples decreased significantly from approximately 80 per cent to 33 per cent. The decline is consistent with a hypothesis of reduced fitness of both resistant homozygotes and heterozygotes relative to susceptible homozygotes under natural conditions.⁵

6.1 What this establishes

That reversion happens in the field, in a real population, on a timescale a pest control programme could plan around. Eighteen months is not geological.

6.2 What it does not establish

That it happens generally. Section 9 is the counter-case and §11 explains why both can be true.

6.3 The design is the part worth copying

Poison a population hard, withdraw entirely, then sample repeatedly over eighteen months with live capture.⁵ That is a straightforward protocol and it produced an unambiguous number.

Nothing comparable exists for any structural insect pest that we could find, which is §23 and also §22. The method is not the obstacle.

7. Reversion in the laboratory

Controlled demonstrations, where the generations can be counted.

A coffee pest selected for organophosphate resistance showed resistance that decreased gradually to low levels and reversed to a completely susceptible status, with resistance recovery and susceptibility occurring in the seventh generation.⁴

An earlier study found that susceptibility of a mosquito vector to the temephos organophosphate insecticide can be recovered by the ninth generation.⁴

7.1 A pyrethroid case with numbers attached

A strain selected with alpha-cypermethrin developed an 11.86-fold resistance level after 12 rounds of selection. The frequency of alpha-cypermethrin resistance decreased when the selected population was reared without further selection pressure for four generations. So, resistance was unstable and reversed when insecticide pressure ceased.²

7.2 Twelve generations up, four generations down

Which is the encouraging asymmetry, and the same study is explicit that the resistance came with measurable fitness costs.²

8. How fast is fast

Putting the three laboratory cases together.

Seven generations, nine generations, four generations.⁴² Different species, different chemistries, same general result: susceptibility came back and it came back quickly.

8.1 The translation problem

A generation is not a unit of time. For a laboratory mosquito it is weeks. For bed bugs under apartment conditions it is considerably longer, and this journal's article on bed bug population biology bears on how much longer.

Seven generations is a rotation interval only if you know the generation time, which in a structural setting depends on temperature, harbourage and host availability. That is our point.

8.2 And resistance comes back faster than it left

The same coffee pest quickly redevelops resistance when the population was again exposed to the chemistry.⁴

Which is what you would expect. The alleles are still present at low frequency and selection merely has to raise them again, so the second selection episode starts from a better position than the first did.

9. The allele that did not go away

The counter-case, and it involves a pest we treat.

The A302S mutation conferring resistance to the cyclodiene insecticides remained under high frequencies in natural populations and the resistance persisted despite the withdrawal of cyclodienes in the field for years, as reported for natural populations of a fruit fly, the German cockroach, and a malaria mosquito.¹

9.1 German cockroaches specifically

This journal has written repeatedly about German cockroach resistance, and this is a documented instance of a resistance allele persisting at high frequency after the selecting chemistry left the market entirely.

Not decaying slowly. Persisting.¹

9.2 The same literature reports the opposite elsewhere

A reduction in the same resistant allele without insecticide selection pressure was observed in natural populations of the horn fly and of an Australian sheep blowfly in both field and laboratory caged strains.¹

One allele, one mechanism, opposite outcomes in different species. Which is the honest state of the evidence and the reason §11 exists.

10. Four chemistries, three decay rates

The experiment from §1, stated properly.

The concept of insecticide rotations as a resistance-delaying tactic was examined in sib populations of a mosquito through the application of selection pressure by single insecticides over several generations followed by relaxation of pressure, and through selection by short- and long-term rotation of the chemicals. Four products were used, and resistance to each chemical showed unequal persistence upon removal from pressure, being most stable for propoxur, least for temephos and intermediate for permethrin.²

10.1 Why this design is the good one

Sib populations control for genetic background. Same starting material, same laboratory, same handling. The only variable is the chemistry, and the chemistry determined the answer.

10.2 The consequence for practice

You cannot look up a decay rate for resistance. You would need one per chemistry per species per population, and the literature contains a handful of such measurements against an enormous space of combinations. That inference is ours.

An earlier review is cited to the effect that the stability of insecticide resistance is influenced by factors such as differences in fitness, initial frequencies of resistant alleles and related parameters,² which is the same conclusion in gentler language.

11. Why a real cost need not produce reversion

The reconciliation, and it has at least five parts.

The next four sections take them in turn. The general shape is that a cost is a force acting on an allele frequency, and forces can be opposed, offset or swamped.

12. Cross-resistance

The simplest explanation and probably the commonest.

The persistence of the resistance allele in an environment free of the withdrawn chemistry might be explained by the allele's cross-resistance with other insecticide that had been continually applied, as well as by the selection of modifiers genes.¹

12.1 What withdrawal actually means

Withdrawing one product does not remove selection on the allele if another product in use selects the same mechanism. The rotation looks like a rotation on the invoice and is not one at the receptor.

This journal's article on rotation made the same point from the practice side, and this is the population-genetic version of it.

12.2 Why structural work is exposed to this

The registered actives available for indoor use in a given pest category are a short list, and mechanistic overlap between them is high. Our article on synergists and metabolic resistance described how a single detoxification pathway can cover chemically unrelated compounds.

13. Compensation and duplication

The population finds a way to keep the resistance and stop paying for it.

In a fruit fly pest resistant to malathion, resistance involving a duplication that produced one susceptible and one resistant mutated copy of the target gene proved more advantageous than the point mutations by maintaining resistance while restoring part of the fitness, allowing the persistence of resistant genotypes for longer time in insecticide-free environments.⁸

13.1 The field observation that demonstrates it

The frequency of the point-mutation allele declined in field populations, when assessed in the same seven localities at 1, 4 and 6 years after malathion withdrawal, whereas the duplication haplotype maintained its frequency during the same period.⁸

13.2 Read that again

In one species, at the same sites, over the same six years after the same withdrawal, one resistance genotype decayed and another did not.⁸

So the question is not whether resistance reverts in a species. It is which resistance mechanism is present, and a monitoring programme that measures only mortality cannot tell you that. This journal's article on molecular diagnostics is the relevant one.

13.3 Modifier genes

The other route is selection on the rest of the genome for changes that offset the cost, which is reported as a general explanation for persistence.¹

The consequence, which is ours, is that a long period of resistance under selection may produce a population that is both resistant and no longer paying, and that delay makes withdrawal less effective the longer you wait to attempt it.

14. Recessive costs and the heterozygote

The dominance argument, which §5 already demonstrated in rats.

If the benefit is dominant and the cost recessive,⁹ then under selection the heterozygote survives and in its absence the heterozygote is close to unpunished.

14.1 What that does to the decay curve

Selection against a recessive cost acts almost entirely on homozygotes, which become rare as frequency falls. The rarer the allele gets, the more of it hides in heterozygotes, and the slower the remaining decay.

So even a genuine cost produces a long tail. That is standard population genetics and we state it as our reasoning applied to these findings rather than as a quoted result.

14.2 And a long tail is enough to defeat rotation

Because the allele does not need to be common for it to be raised quickly on re-exposure.⁴ It needs only to be present.

15. Small populations do not behave like models

The awkward finding for anybody projecting a decay curve.

In a large-scale study of rats, the population does not seem to be in equilibrium, but rather under constant gene flux probably due to drift caused by small population sizes.¹²

15.1 Why this is a structural pest control problem specifically

Populations in buildings are small, isolated and repeatedly bottlenecked by treatment. Those are precisely the conditions under which drift overwhelms weak selection.

A fitness cost of a few per cent is a reliable force in a population of millions and noise in a population of dozens, which is the situation in a single structure. That application is ours.

15.2 It cuts both ways

Drift can eliminate a resistance allele from a small population by chance as easily as it can fix one. What it cannot do is make the outcome predictable, and predictability is what a rotation schedule requires.

16. The measurement problem

Why the literature is as mixed as it is, in the authors' own assessment.

One has to consider that the evaluation of the overall fitness effects of a given mutation is very challenging, once it is difficult to separate their own effects from those caused by other mechanisms possibly coselected for resistance. In the cyclodiene examples, the reduced fitness might be related to the target-site mutation itself, and/or to metabolic resistance mechanisms.¹

16.1 What gets selected is a genome, not a mutation

A strain selected in the laboratory acquires the resistance allele and whatever else was linked to it or selected alongside it. Attributing the measured fitness difference to the named mutation is an inference.

The remedy is the congenic or quasi-congenic design, in which the allele is bred into a common background over several generations, as was done for the position 139 rat strain.¹⁴ It is slow, and most published fitness measurements do not do it.

16.2 Which should temper the numbers in this article

Including the ones we have quoted approvingly. A reported fitness cost of a given percentage is an estimate of the difference between two strains, not a measurement of what one mutation does, unless the design controlled for background.

16.3 And it explains part of the disagreement

If different laboratories select different genetic backgrounds and measure the resulting difference, they will get different costs for nominally the same mutation. Some of the variance described as large³ may be variance in method rather than in biology.

We cannot quantify how much, and we have seen no source that attempts to. That is our observation.

17. Decades, not seasons

The modelling result that sets the outer bound.

A stage-structured deterministic model parameterised for a dengue vector investigated the time for a population which displays resistance to insecticide to revert to a susceptible population as a function of fitness costs and initial allele frequency. Applied to field data, it indicates that reversal can take, in some cases, decades even if fitness costs are not small.³

17.1 Even if fitness costs are not small

That is the clause to keep. The result is not that reversion fails when costs are absent. It is that reversion can take decades when costs are substantial.³

17.2 The dependence on starting frequency

The authors produced a map of reversal time as a function of either cost or initial presence of the resistance allele in the population, offered as both a guiding and a surveillance tool.³

A population at 90 per cent resistant has much further to fall than one at 20 per cent, so the same cost produces very different waiting times. Which means the answer to how long to rotate away depends on how bad the resistance already is, and almost nobody measures that.

18. What this does to rotation

The practical conclusion, stated carefully.

Rotation is not refuted by any of this. A chemistry withdrawn is a chemistry not being selected for, and several of the cases here show real and fairly rapid recovery.⁵⁴²

18.1 What is refuted is the schedule

The idea that a fixed interval away from a product restores its efficacy. The interval that would be required is chemistry-specific, mechanism-specific, population-specific and, in the cyclodiene case, apparently infinite.¹²

18.2 The honest version of the claim

Rotation reduces the rate at which resistance accumulates to any single chemistry. It does not reliably restore a chemistry that has already failed.

Those are different claims and the trade routinely states the second while having evidence only for the first, which is our assessment and follows this journal's article on rotation evidence.

18.3 The authors of the reversion study drew the same practical conclusion

They proposed that thresholds, biological and physical controls, and rotations of insecticides with different mechanisms may assist resistance management, with rotation timed a generation before the observed reversion point.⁴

Note the order. Thresholds first, physical controls second, rotation third. That matches this journal's article on injury levels and action thresholds, and it is not the order the trade uses.

19. Structural pest control is the difficult case

Collecting the reasons this literature translates badly into buildings.

Generation times are long and temperature-dependent. Seven generations is a laboratory phrase and an unknown number of months in a wall void.

Populations are small. Which makes drift dominant over weak selection, per §15.¹²

Selection is continuous rather than seasonal. Agricultural populations experience treatment windows and untreated refuges. A treated apartment building has neither, and this journal's article on bed bug chemical ecology described the absence of an untreated refuge.

Mechanistic overlap is high. The available indoor actives are few, so the cross-resistance route in §12 is close to unavoidable.¹

And nobody measures the starting frequency. Which §17.2 identifies as the variable that determines the waiting time.³

And treatment is repeated on the same population. An agricultural field is recolonised from surrounding untreated ground between seasons. A sealed apartment block is treated, survives, and is treated again, so the survivors of each round are the founders of the next.

19.1 The honest summary

Every condition that makes reversion fast in the published cases is absent or reversed in structural work. We think that is the most useful thing in this article and it is our reasoning, not a sourced finding.

20. The induction finding

A result that sits awkwardly with the whole framework and deserves flagging.

Susceptible Norway rats were screened with a sublethal dose of warfarin from the generation F0 to F5, after which the warfarin tolerance level of the screened rats was significantly improved, with tests indicating 5.7 to 7.1% of screened rats were resistant, while all unscreened rats were susceptible. Analysis suggested none of the screened animals carried any potential warfarin resistance target-gene mutations.⁷

20.1 Resistance without the resistance allele

Tolerance rose across six generations of sublethal exposure with no detectable mutation in the gene everyone monitors.⁷

If tolerance can accumulate through a route the standard genetic test does not detect, then a molecular monitoring programme can return a clean result on a population that is becoming harder to kill. That is our reading and it qualifies this journal's article on molecular diagnostics.

20.2 With a cost attached

As a fitness cost, the litter size of the screened rats tended to be smaller over generations, implicating the reproductive success could be impacted by warfarin induction.⁷

20.3 The practical warning

Sublethal dosing is the mechanism. Under-baiting, short campaigns and partial bait uptake are sublethal dosing, and this journal's articles on anticoagulant practice and on rodent behaviour both described how readily that happens in the field.

21. What a contractor can actually do

Since the useful conclusion is not that rotation is pointless.

Rotate by mechanism, not by product name. Cross-resistance in §12 makes label diversity meaningless if the mode of action or the detoxification route is shared.¹

Do not assume a returned chemistry has recovered. Test it or accept that you are gambling. The cyclodiene case is the reason.¹

Treat sublethal exposure as the enemy. Full label rate, adequate coverage, enough bait for long enough. Sections 20 and 7.2 both point the same way.⁷²

Use non-chemical control to carry the load. Heat, exclusion, sanitation and physical removal impose no selection. This journal has covered each of them, and every one of them buys time that rotation cannot reliably buy.

And measure before concluding. Bioassay or molecular testing tells you which mechanism is present, and §13.2 shows that the mechanism determines whether withdrawal will work at all.⁸

21.1 Our own position

We are a pest control contractor and rotation is standard practice in this trade, including ours. Nothing here says stop rotating. It says the claim that a rested chemistry comes back is a claim requiring evidence in each case, and the trade generally asserts it without any.

Where we recommend a chemistry that previously failed at a site, the client is entitled to ask what evidence we have that susceptibility has returned. The honest answer is usually none, in which case the right move is a different mechanism rather than a rested one.

22. The Manitoba position

What is and is not known locally.

There is, to our knowledge, no published resistance monitoring for any structural pest in Manitoba. No baseline susceptibility data, no allele frequency survey, no record of which mechanisms are present in local bed bug, cockroach or rodent populations.

22.1 Which makes §17.2 unanswerable here

The waiting time for reversion depends on the starting frequency,³ and nobody in this province knows the starting frequency for anything.

This journal has now identified the same gap in several articles. It is the single most useful piece of research anybody with a laboratory and a modest budget could do for pest control in this province, and it would not be expensive.

23. Limitations and open questions

The structural literature is thin to absent. Almost every case here is agricultural, veterinary or vector control. The German cockroach cyclodiene observation is the main exception and it is reported secondhand within a review.¹

Two sources are repository listings rather than primary papers. The fitness cost and stability material and the wild rat commentary reach us through aggregator pages summarising the underlying work, and we have not seen the full papers.²¹²

Publication bias is likely and unquantified. A study finding reversion has a clean result to report; a study finding nothing changed over six generations is harder to publish. We cannot assess how much this shapes the picture.

The bed bug case is absent. We found no data on whether pyrethroid resistance in bed bugs reverts, which is the question a structural contractor most wants answered. Its absence is itself worth recording.

Laboratory selection is not field selection. Laboratory strains are selected hard and fast on small founder populations, which is not how a field population acquires resistance,¹¹ and the reversion rates may not transfer for the same reason.

The vitamin K cost may not express in commensal rodents. It was measured under induced deficiency,⁶ and §5.2 is our argument about what that means in a city, not a finding.

Sections 1.1, 2.1, 5.1, 5.2, 8.1, 8.2, 10.2, 12.2, 13.2, 13.3, 14, 15.1, 15.2, 16.1, 18, 19, 20.1, 20.3, 21 and 22 are our reasoning. The absence of a general decay rate, the translation of generations into structural time, the heterozygote argument, the drift argument, the small-population application, the reading of the duplication result, the distinction between slowing accumulation and restoring efficacy, the structural difficulty list, the monitoring warning from the induction study and the practical recommendations are ours rather than sourced positions.

24. Conclusion

The fitness cost is real. In brown rats it is a vitamin, with resistance and an increased vitamin K requirement described as pleiotropic effects of the same allele,⁵ and a wild population fell from roughly 80 per cent resistant to 33 per cent in the eighteen months after the poison was withdrawn.⁵ Laboratory populations have recovered susceptibility at the fourth, seventh and ninth generations in three different systems.²⁴

And the cyclodiene resistance allele has been reported at high frequency in natural populations of the German cockroach and others years after the chemistry left,¹ a gene duplication in a fruit fly held its frequency for six years after withdrawal while the point mutation beside it declined,⁸ and a model of a mosquito vector found reversal taking decades even where fitness costs are not small.³ Four insecticides applied to sib populations of one species decayed at three different rates.²

So the cost exists and does not reliably produce the recovery, because cross-resistance keeps selecting the allele, compensating changes remove the penalty, recessive costs let heterozygotes carry it free, and small populations are governed by drift rather than by weak selection. Every one of those conditions is stronger indoors than in the fields where the reversion data were collected. The defensible claim is that rotating between mechanisms slows the accumulation of resistance. The claim that a rested chemistry comes back is a separate one, it is true in some documented cases and false in others, and nobody currently has the local data to tell which case a Winnipeg building is in.

References

1. Insecticide Resistance and Fitness Cost. Open-access book chapter reviewing fitness effects of resistance mutations. Used for the report that the A302S mutation remained at high frequencies in natural populations and that resistance persisted despite withdrawal of cyclodienes in the field for years, in a fruit fly, the German cockroach and a malaria mosquito; for the contrasting report of a reduction in the same resistant allele without insecticide selection pressure in natural populations of the horn fly and of an Australian sheep blowfly in both field and laboratory caged strains; for the statement that evaluation of the overall fitness effects of a given mutation is very challenging because it is difficult to separate their own effects from those caused by other mechanisms possibly coselected for resistance, and that the reduced fitness in these examples might relate to the target-site mutation itself and or to metabolic resistance mechanisms; for the explanation that persistence of a resistance allele in an environment free of the withdrawn chemistry might be explained by cross-resistance with another insecticide that had been continually applied as well as by selection of modifier genes; and for the observation that in the absence of insecticides susceptible individuals may present reproductive advantages with a consequent fall in population resistance level. https://www.intechopen.com/chapters/49941
2. Insecticide Resistance Fitness Cost and Resistance Stability. Research repository record for a study of a pyrethroid-selected strain, together with the linked abstracts it reproduces. Repository listing rather than the primary paper, cited as attributed material. Used for the report that an alpha-cypermethrin selected strain developed an 11.86-fold resistance level after 12 rounds of selection compared with the unselected strain; that the relative fitness of the selected strain and of both reciprocal crosses was significantly less than that of the unselected strain, indicating fitness costs; and that the frequency of resistance decreased when the selected population was reared without further selection pressure for four generations, so that resistance was unstable and reversed when insecticide pressure ceased. Also used for the reproduced account of a rotation experiment in which the concept of insecticide rotations as a resistance-delaying tactic was examined in sib populations of a mosquito through application of selection pressure by single insecticides over several generations followed by relaxation of pressure, and through short- and long-term rotation, using four named products, with resistance to each chemical showing unequal persistence upon removal from pressure, most stable for propoxur, least for temephos and intermediate for permethrin; and for the cited proposition that the stability of insecticide resistance is influenced by factors such as differences in fitness and initial frequencies of resistant alleles. https://www.researchgate.net/publication/269099417_Insecticide_Resistance_Fitness_Cost_and_Resistance_Stability
3. Costly Inheritance and the Persistence of Insecticide Resistance in Aedes aegypti Populations. Open-access modelling study. Used for the use of a stage-structured deterministic model parameterised for a dengue vector to investigate the time for a resistant population to revert to a susceptible one as a function of fitness costs and initial presence of the resistance allele; for the resulting map offered as both a guiding and a surveillance tool for public health officers; for the finding that application to field data indicates reversal can take, in some cases, decades even if fitness costs are not small; for the statement that insecticide resistance usually comes with associated fitness costs and that these have a large variance ranging from nearly absent to very high; and for the note that resistance costs are usually reported in association with reduced lifespan and oviposition rates and sometimes longer maturation times, and that the question of how resistance costs impinge on life parameters is a large and controversial one. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416794/
4. Fitness cost and reversion of resistance of a coffee leaf miner to chlorpyrifos. Journal article in an ecotoxicology and environmental safety title. Used for the finding that the species quickly redevelops resistance when the population is again exposed to the chemistry; that resistance decreased gradually to low levels and reversed to a completely susceptible status, with resistance recovery and susceptibility occurring in the seventh generation; for the cited earlier finding that susceptibility of a mosquito vector to the temephos organophosphate can be recovered by the ninth generation; for the conclusion that withdrawal of the insecticide from the market reduces selection pressure in a way that may lead to regression of resistance alleles; and for the authors' recommendation that thresholds, biological and physical controls, and rotations of insecticides with different mechanisms may assist insecticide resistance management programmes. https://www.sciencedirect.com/science/article/pii/S0147651322006716
5. Relative fitness of genotypes in a population of Rattus norvegicus polymorphic for warfarin resistance. Journal article in a genetics title. Used for the statement that resistance to warfarin and an increased vitamin K requirement appear to be pleiotropic effects of the same allele; for the study design in which a large polymorphic population of rats was extensively poisoned with warfarin and the level of resistance monitored regularly for 18 months after withdrawal of the poison; for the result that during this period the proportion of resistant animals in live-capture samples decreased significantly from approximately 80 per cent to 33 per cent; and for the authors' interpretation that this decline is consistent with a hypothesis of reduced fitness of both the resistant homozygote and the heterozygote relative to the susceptible homozygote under natural conditions. https://www.nature.com/articles/hdy197979
6. Vitamin K requirement and reproduction in bromadiolone-resistant Norway rats. Journal article in a pest management science title. Used for the statement that nucleotide polymorphisms in the target gene can be linked to anticoagulant rodenticide resistance in Norway rats, providing a fitness advantage to rats exposed to anticoagulant actives but potentially also causing fitness costs; for the comparison of vitamin K requirement and reproductive parameters between a resistant strain carrying a position 139 variant and susceptible rats; and for the finding that at vitamin K deficiency blood clotting times increased in all homozygous resistant males within 8 days and in 80 per cent of homozygous resistant females within 15 days, with little effect on blood clotting in heterozygous males and no effect in heterozygous females. https://scijournals.onlinelibrary.wiley.com/doi/10.1002/ps.2273
7. Sublethal dose of warfarin induction promotes the accumulation of warfarin resistance in susceptible Norway rats. Journal article in a pest science title. Used for the statement that resistance to anticoagulant rodenticides in Norway rats has been primarily explained by selection on mutations in the vitamin K epoxide reductase complex subunit 1 gene, and that whether warfarin resistance can be induced independently of those mutations was unclear; for the design in which susceptible rats were screened with a sublethal dose from generation F0 to F5; for the finding that the warfarin tolerance level of the screened rats was significantly improved, that lethal feeding period tests indicated 5.7 to 7.1 per cent of screened rats were resistant while all unscreened rats were susceptible, and that none of the screened animals carried any potential warfarin resistance mutations in that gene; and for the observation that as a fitness cost the litter size of the screened rats tended to be smaller over generations, implicating reproductive success. https://link.springer.com/article/10.1007/s10340-020-01299-3
8. Reduced fitness cost accounts for the stability of a malathion-resistant heterogeneous duplication haplotype in field populations of a fruit fly pest. Journal article in a pest management science title. Used for the finding that resistance was inherited as a semi-dominant trait; that the point-mutation allele imposes a higher fitness cost than the duplication haplotype by three lines of evidence, namely reduced performance of homozygous individuals for some biological traits, greater stability of the duplication haplotype under laboratory conditions in the absence of insecticide selection, and decline of the point-mutation allele frequency in field populations assessed in the same seven localities at 1, 4 and 6 years after malathion withdrawal while the duplication haplotype maintained its frequency over the same period; and for the interpretation that heterogeneous duplications producing one susceptible and one resistant mutated copy are more advantageous than point mutations by maintaining resistance while restoring part of the fitness, allowing persistence of resistant genotypes for longer in insecticide-free environments. https://scijournals.onlinelibrary.wiley.com/doi/10.1002/ps.71269?af=R
9. Beneficial reversal of dominance maintains a resistance polymorphism under fluctuating insecticide selection. Preprint, not peer reviewed at time of access, flagged accordingly. Used for the account that organophosphate insecticides act as irreversible inhibitors of acetylcholinesterase and have imposed seasonally fluctuating selection pressures on resistant insect populations, as seen in seasonal resistance fluctuations in field studies; for the statement that following Wright's physiological theory of dominance resistant alleles should be loss-of-function and thus recessive in pesticide-free environments while sensitive alleles should become loss-of-function and thus recessive in pesticide-rich environments; and for the summary that previous studies across resistant insect populations suggest resistant alleles of the target gene follow patterns of beneficial reversal of dominance, often showing dominant benefits and or recessive costs for fitness-associated traits, though direct evidence is lacking. https://www.biorxiv.org/content/10.1101/2024.10.23.619953.full.pdf
10. Norway rat entry, rodenticide resistance action committee resistance guide. Industry working group resource, flagged as attributed material. Used for the account that physiological fitness costs would usually be expected to decrease the incidence of resistance in rodent populations in the absence of anticoagulant selection; for the history that resistance was later linked to the vitamin K epoxide reductase complex subunit 1 gene encoding an anticoagulant-sensitive component of the enzyme; and for the statement that a number of region-specific sequence variants developed independently in this gene, each conferring a certain level of resistance, and that among variants with confirmed impact on resistance status mutations at position 139 are the most frequent. https://guide.rrac.info/rodenticide-molecules/norway-rat.html
11. Experimental evolution of insect resistance to two pesticide classes reveals mechanistic diversity and context-dependent fitness costs. Preprint, not peer reviewed at time of access, flagged accordingly. Used for the experimental design in which populations were selected on control or pesticide diets for eight generations, selection was then relaxed for two generations and the resulting populations exposed to pesticides with mortality measured; for the observation that control populations varied in their susceptibility to the same dose at the outset; and for the finding that after eight generations of organophosphate or pyrethroid selection all selected populations showed significantly increased survival compared with controls but varied in their relative mortality rates, with the accompanying characterisation of fitness costs as context-dependent. https://www.biorxiv.org/content/10.1101/2021.09.03.458899.full.pdf
12. A New Aspect of Warfarin Resistance in Wild Rats: Benefits in the Absence of Poison. Research repository record and the linked material it reproduces. Repository listing rather than the primary paper, cited as attributed material. Used for the investigation of whether warfarin resistance imposes a fitness cost by reducing energy available for growth, using lines homozygous for two regional resistance alleles established on a common genetic background; for the statement that it seems likely that when rodenticide use ceases the selection pressure should turn against anticoagulant resistance, but that this did not occur in every context; and for the report that in a large-scale study the rat population does not seem to be in equilibrium but rather under constant gene flux, probably due to drift caused by small population sizes. https://www.researchgate.net/publication/273077648_A_New_Aspect_of_Warfarin_Resistance_in_Wild_Rats_Benefits_in_the_Absence_of_Poison
13. Consequences of the Y139F Vkorc1 mutation on resistance to antivitamin K compounds: in-vivo investigation in a seventh generation of a congenic strain of rats. Open-access pharmacogenetics article. Used for the account that the gene encoding an anticoagulant-sensitive component of the vitamin K epoxide reductase is the subunit 1 gene; that since its discovery various amino acid and transcription-regulatory altering mutations have been identified in wild rodent populations that were difficult to control with anticoagulant rodenticides; for the unresolved question of the dependency of the gene on genetic background; and for the breeding of a quasi-congenic strain using a wild-caught resistant rat as donor to introduce the position 139 amino acid change into the background of a susceptible recipient strain, with results reported in the seventh generation. https://pmc.ncbi.nlm.nih.gov/articles/PMC3102556/
14. Biochemistry of resistance to warfarin in a French strain of the Norway rat. Journal article in an international pest management title. Used for the study of warfarin-susceptible and warfarin-resistant strains to determine the mechanism of resistance; for the identification of the position 139 variant among previously described mutations in the target gene; and for the kinetic finding that in resistant rats enzyme activity was lower and also less inhibited by warfarin than in susceptible rats, with both the maximum rate and the affinity constant lowered, so that the enzymatic efficiency was similar between resistant and susceptible rats. https://www.tandfonline.com/doi/abs/10.1080/09670870701549640