# Resistant mites: a doubt



## Eduardo Gomes (Nov 10, 2014)

Resistance to miticides really exist, at least as we conceive it?

or 

inbreeding system of reproduction in mites it allows a much higher genetic diversity and phenotypes much more diverse than what we suppose?


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## Dan the bee guy (Jun 18, 2015)

To have resistance to something you have to have the right genes you don't get resistance by being exposed to something. If you have 10000 hives you have thousands of mites in each hive chances of having 1 mite that has the right genes is pretty good. that is why rotation of treatments is the way to prolong the life of the treatment


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## JohnBruceLeonard (Jul 7, 2015)

This is a very interesting point, Eduardo. I am extremely ignorant about many facets of this issue, so let me ask a few questions. It may be that one or more of the following points can help explain the discrepancy you are seeing.

First, is it necessarily the case, that _all _mite survivors of a given treatment, survive_ on account of resistance_? Or might there also be "accidental" survivors? (Say, for example, a mite that is too far away from the source of the treatment to be immediately affected by it.)

Second, of those mites that _do _survive on account of resistance, is this resistance _total, _or _partial_?

Third, (behold my shameful ignorance of genetics), does a female mite necessarily express _all _the genetic traits of her mother? Furthermore, does _her _daughter, supposing that daughter is produced by this mite's inbreeding with her own brother, necessarily express _all_ the traits of her grandmother? Put otherwise - given a mite lineage produced strictly of inbreeding, is it _necessarily the case_ that resistance is passed, or perfectly passed, from generation to generation?

John


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## Richard Cryberg (May 24, 2013)

Eduardo Gomes said:


> Suppose that on January 1, 2016 I have a hive with 2 mites resistant to amitraz on the Apivar. These two mites over 2016 may generate more than 28 000 resistant mites in one year to the amitraz on the Apivar. I get this number (28 000) starting with 2 resistant mites x 18 breeding cycles in one year multiplied by a factor of 1.7.
> 
> My question is: where is failing my reasoning and/ or my numbers because of amitraz Apivar in my experience does not lose its effectiveness after its first use.


There are lots of genetic combinations that potentially lead to resistance. Resistance happens when one of several things happens. It could be some mutation or combination of mutations results in much poorer uptake of the chemical. It could be because metabolism of the chemical happens faster. It could be because of differences in transport of the chemical inside the insect. Etc. None of these have to be like a light switch that is either off or on. Much more likely there will be degrees of resistance with some combinations of genetics being more or less resistant. So, viewing resistance as the effect of a single mutation change is rather unlikely. More likely it is a combination. For calculations lets just assume the single mutant case as that is the only simple one to do any type of calculations on.

That single mutant can be either dominant, recessive or codominant. It can also have expressivity or penetrance issues in any of these cases. So, even a single mutant issue is not like a light switch. The only two possiblities that are easy to calculate are pure recessive or pure dominant without expressivity or penetrance issues so lets consider them.

First pure recessive. In order to express the mite needs two copies. As long as there is only a single mite in the cell 100% of the offspring will express as the founder must be homozygous to express. Using your numbers of 1.7 offspring per founder if you started with a large number of resistant founder mites in 18 generations you would get the about 28,000 offspring you calculated from two mites. The math is (1.7**18)x2. But, each mite can not have 1.7 offspring per generation. They can have one or two of three but not fractions. They can also have zero that survive. So, the above math really only works for a fair population of founders. At least 10 or 20 founders. For one founder or two founders the number after 18 generations can vary wildly and be as little as zero and almost for sure some number well under 28,000.

For a pure dominant mutant the numbers are a bit different. Those founder mites are more than likely heterozygous for the mutant. So in the first generation half the young will also be heterozygous as it is very unlikely that the founder mated to a resistant brother. So, half the first generation young are not resistant and die. In the second generation The sperm from the male may be either 100% resistant or 100% non resistant so the third generation can be a some combination of non resistant that die, homozygous resistant and heterozygous resistant. Slowly over time the Hardy Weinberg equillibrium will shift towards 100% homozygous but this will take many generations. The net result is every generation some young are not resistant and die and add in that for only two founders you get into the same statistical problems of random distribution of young on an integer basis and your final number of survivors is going to be WAY below that 28,000 you calculated. Even for a founder population of 10 or 100 resistant mites it would be way below what you calculated per mite due to all the homozygous non resistant progeny that die as you no longer have 1.7 resistant mites per generation, but some smaller number.

In all cases you also have to consider the effect of having more than one founder per cell. In a mixed population the second founder is likely to be non resistant and if its male crosses with the resistant females you further dilute the resistant mutant resulting in numbers below your worst case calculation for both the pure recessive and pure dominant mutants. Then there is the fact that a hive with 10,000 mites is a dead hive, probably within a few weeks, and many of those resistant mites are going to die with the hive and never reproduce at all, again lowering the ultimate calculated number. It is even quite possible that a fully resistant mutant does other things to the mite that make it less fit and result in lowering its reproduction rate. This is in fact quite probable as any such mutant is going to carry some sort of metabolic cost. If that metabolic cost is very high the mutant will more than likely die out entirely and cease to exist.

My point in this is to point out that resistance is a very complex matter and involves a great many different factors which are all very important in how well the mutant does. It is even possible that resistance could come at such a metabolic cost that it would be beneficial as you could kill all non resistant mites and only have resistant mites which could do very little more than hold their own population wise. In such a case a bit of drone comb removal and continued occasional application of pesticide to take care of revertants could be a easy way to control mite levels to non problem counts.

Some insects have some metabolic chemistry that can be adapted to resist far before first exposure while other insects lack such chemistry. DDT is a fine example. Flies did not take very long to develop massive resistance to DDT while mosquitoes have not developed resistance to today for exactly that reason. Still, it is a best bet that given enough time and enough exposure mites will become resistant to amatraz.

Dick


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## Dominic (Jul 12, 2013)

Eduardo Gomes said:


> About resistant mites I've done some accounts and there is one thing that does not fit in my knowledge, which are few and very incomplete and so I call for your help.
> 
> Resistances result in a peculiar characteristic of the mite which makes it resistant to a particular product acaricide . This mite reproduces inbreeding and the odds that they pass this trait to their offspring is extremely high given the peculiarities of its reproduction process. We know that on average each reproductive cycle of the mites it multiply by a factor of 1.7 the previous number. We know that each reproductive cycle takes about 20 days to complete up roughly. Doing the calculations we have about 18 reproductive mite cycles over a year.
> 
> ...


I didn't run your math, nor verify the population growth dynamics, but presuming the resistance lies upon a single allele (possible but not necessarily), sounds reasonable. For more information on varroa population dynamics, this article can be of help (though a quick scan of it raises more questions than it answers): http://www.ars.usda.gov/SP2UserFile...00/412-Harris--Variable Population Growth.pdf

That being said, I do have some doubts on the numbers themselves. Most treatments have around 95% kill at best. That leaves 1400 resistant mites after 1 year, assuming you did a different treatment (say OA) at that time. Plus the offspring of whatever mites had survived due to factors other than resistance. Plus the offspring of any incoming mite if there's a positive migratory balance (more varroa coming in from other hives than leaving for other hives). With these numbers, even treating once per year would pretty much guarantee you'd lose your hives on the second year. While treating twice per year is not uncommon, with the numbers you give, I'm left with the impression that it would result in the same problem (albeit at a lesser scale). Which begs the question of how many treatments per year would be required to reach an equilibrium, where mite kill per year is equal mite growth per year. I've heard stories of some people doing more than three treatments per year (talk about susceptible bees!), but I don't think that's the norm?

If the resistance lies upon multiple alleles, the dynamics are a bit different, though.


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## Eduardo Gomes (Nov 10, 2014)

Thank you all!

>>Put otherwise - given a mite lineage produced strictly of inbreeding, is it necessarily the case that resistance is passed, or perfectly passed, from generation to generation?>> Bruce an excellent question, and which also reflects my doubts and knowledge gaps.

>>Much more likely there will be degrees of resistance with some combinations of genetics being more or less resistant. So, viewing resistance as the effect of a single mutation change is rather unlikely. More likely it is a combination.>> Great genetics lesson. Dick I was in need of it. If not boring can you tell us why do you believe that resistance is probably based on a combination of mutations and not a single one? What implications should be taken for accurate varroa control strategy of different degrees of resistance?

>> Which begs the question of how many treatments per year would be required to reach an equilibrium, where mite kill per year is equal mite growth per year.>>
Dominic do you do the treatments by de calendar or guide your strategy according to IPM, or is a mixture of both?


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## Richard Cryberg (May 24, 2013)

Eduardo Gomes said:


> If not boring can you tell us why do you believe that resistance is probably based on a combination of mutations and not a single one? What implications should be taken for accurate varroa control strategy of different degrees of resistance?


Just about everything is more than one single mutant. If you took genetics more than 20 years ago you likely were taught eye color (blue vs brown) is a one gene difference and two blue eyed parents can not have a brown eyed kid. Pure BS on both items. Same with ear lobes being one gene, how you taste bitter and on and on. Sure, occasionally you do run into examples like Mendel worked on with his peas that are clean single gene effects. But, as soon as you do any serious genetics you will realize that such simple situations are the exception and far more often there are two, three or more genes involved. This was first realized in 1875 when a world famous mathematician Francis Galton published his analysis of several human traits. Unfortunately biologists did not pay any attention to mathematics until after about 1980 so none of them seem to have read his papers. As an aside Galton was Darwin's cousin.

At some level every thing is a poison. That includes drinking water. Just drink a gallon and a half in an hour and a half and see how dead you become fairly rapidly. People die every year from drinking too much water too fast. And at some level everything is safe. That safe level can be viewed as resistance. So, there are no general implications as the safe level rises (as resistance increases) because every case is going to be different.


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## Fusion_power (Jan 14, 2005)

I'd like to illustrate that statement re everything being more than one mutant to make it easier to understand. Here is the chemical sequence at a high level to produce carotenoids in tomato. Each line item represents a gene that performs a function. I capitalized each gene mnemonic.

Start with geranylgeranyl pyrophosphate (GGPP) as the initial chemical input
PSY - chains 15-Cis-Phytoene and then to Phytofluene
PDS - chains tri-cis-carotene
ZISO - converts to di-cis-carotene
ZDS - converts to neurosporene then prolycopene
CrtISO - converts prolycopene to all trans lycopene = red fruit
Cyc-B - converts lycopene to y-lycopene, Cyc-A results in delta carotene
Beta - grabs the y-lycopene and chains the ends together to form Beta Carotene
MO-B - is a modifier with normal and recessive forms, the recessive up-regulates Beta Carotene.

If you interrupt this chain at PSY, you get a recessive yellow tomato. Interrupt it at CrtISO, you get recessive tangerine. Complete CrtISO and you get a normal red tomato, this is the common tomato we are all familiar with. A gene variant at Cyc-B results in delta carotene which is an orange/red color. Carry the chain to completion with Beta and you get a carrot orange tomato, but this particular gene is dominant and will always override normal red. A modifier gene, mo-b up-regulates Beta to produce a super beta tomato that contains up to 40 times the beta carotene of normal tomatoes as shown in 97L97, a breeding line produced by John Stommel.

The point is that a high level trait such as fruit color is a result of a complex "biopath", not just a single gene trait. Another good example is the way fruit size is determined in tomato. One gene turns on production of a special type of cell that forms fruit walls. Another gene turns off proliferation of that cell. You can make small tomatoes by either limiting the first gene or by prematurely turning it off with the second gene. Both conditions are dominant. Only the combination of turning on the fruit size gene and a defective gene to turn it back off results in large slicing tomatoes. Add in the effect of genes that cause fused ovules (beefsteak tomatoes), elongated fruit (Roma tomatoes), decreased water content (paste tomatoes), increased fruit sugar (this is a highly complex biopath leading to candy sweet tomatoes like Sungold) and you have a recipe for the incredible diversity of modern tomatoes.


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## Eduardo Gomes (Nov 10, 2014)

Thank you Dick and Dar!

Can advise me a good book or link on the Internet, but not too complex, where it can inform me about genetics in bees?


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## Harley Craig (Sep 18, 2012)

Fusion, that is a great response. Who knew tomatoes were so complex? Seriously interesting stuff.


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