How did genetic capacity for allergies not get weeded out?

[ScienceNostalgia101]

The idea that our immune systems would mistake food of all things for something harmful sounds bizarre. The idea that it would react to a lethal extreme to anything sounds even more bizarre. Surely even if it thinks the threat is lethal, obviously the response would have to be just shy of lethal to be of any help at all. Yet we hear of life-threatening allergies to food items of all things all the time.

 

How did life-threatening allergies to food items not result in enough anaphylaxis deaths over the course of evolution to leave behind only the genes that tell the immune system how to tell food from life-threatening pathogens? Or at least tell the body there's no point fighting a lethal pathogen with an even more lethal response?

[exchemist]

9 minutes ago, ScienceNostalgia101 said:

The idea that our immune systems would mistake food of all things for something harmful sounds bizarre. The idea that it would react to a lethal extreme to anything sounds even more bizarre. Surely even if it thinks the threat is lethal, obviously the response would have to be just shy of lethal to be of any help at all. Yet we hear of life-threatening allergies to food items of all things all the time.

 

How did life-threatening allergies to food items not result in enough anaphylaxis deaths over the course of evolution to leave behind only the genes that tell the immune system how to tell food from life-threatening pathogens? Or at least tell the body there's no point fighting a lethal pathogen with an even more lethal response?

If such allergies affected a significant proportion of the population and involves enough of the foodstuffs consumed then it would generate evolutionary pressure, I'm sure. But as it affects only a small fringe of people, I suppose it's possible that the rate at which allergies arise is in balance with the rate of extinction of them.  There are examples of food intolerance modifying a population, for instance the ability of adult N Europeans to consume animal milk without trouble, whereas lactose intolerance in adults is the default in many populations originating outside N Europe.   

[iNow]

Part of the answer here also involves exposure during childhood and how paradoxically our quest for increasingly antibacterial homes through powerful cleaning agents is making our immune system defenses less capable and us more prone to exaggerated response in the face of seemingly innocuous stimuli. 

[Peterkin]

24 minutes ago, ScienceNostalgia101 said:

How did life-threatening allergies to food items not result in enough anaphylaxis deaths over the course of evolution to leave behind only the genes that tell the immune system how to tell food from life-threatening pathogens?

Couple of ways. One is how evolution works: by trial and error. Most of the allergic people didn't die before they could reproduce. Many others were saved from a much worse threat of infection or poisoning by a related system of immune responses. The other is how humans change their own environment and breeding practices. Some of the foods to which people are allergic didn't exist in the same form in the environment in which humans evolved. Further, some of the waste products of our industries also affect cellular function. 

As exchemist pointed out, we do adapt to new environmental factors, but it takes many generations, and human regeneration has a long turnover cycle.

24 minutes ago, ScienceNostalgia101 said:

Or at least tell the body there's no point fighting a lethal pathogen with an even more lethal response?

You can't "tell the body" anything, though you can modify its activity with chemical interventions. The immune system of humans is complex; when you try to shut down a reaction you consider inappropriate or inconvenient, you risk shutting down a vital function along with it. Thus the need to be exceptionally careful in the application of immunosuppressant drugs, in e.g. transplant situations. Suppression of minor, superficial manifestations can be temporarily controlled by antihistamines.   

Edited August 7, 2022 by Peterkin
keep leaving out small words

[mistermack]

Allergies, like a lot of disorders, are thought in many quarters to be the result of the lifestyle of modern humans. Research indicates that stone-age people didn't suffer from a whole raft of problems that are common now, like obeisity, high blood pressure, allergies and heart disease. 

Some studies indicate that exposing babies to dirt etc actually primes their immune system in a healthy way, even if it intitially makes them a bit sick. Our ancestors evolved in Africa, living outdoors, and babies would be putting anything they picked up into their mouths, just as they do now. And the mother's wouldn't be stopping them, or taking much notice. It's a totally different start to life compared to today.

[MigL]

While genetic programming is 'hardwired', and affects populations because it is passed on from one generation  to the next, the immune system works on a 'learned response', and why allergies come and go with age, change severity, and are not passed on.

[ScienceNostalgia101]

Thanks for the clarification, everyone. I vaguely heard of lifestyle as a factor in allergies before but wasn't sure whether this was a fringe notion or not... seems not.

[CharonY]

2 hours ago, ScienceNostalgia101 said:

Thanks for the clarification, everyone. I vaguely heard of lifestyle as a factor in allergies before but wasn't sure whether this was a fringe notion or not... seems not.

Well, but that is not all of it. The way our immune system works simply has the room for error. It is inbuilt and unlikely to be weeded out by selection. The hygiene hypothesis is just one hypothesis, others include change in diet. In both cases the assumption is that being exposed to something different to what our immune system evolved to tackle with might cause allergies. 

However, there are others including the toxin hypothesis, which proposes that allergic response are triggered by our immune system dealing with potentially poisonous substances and that it doesn't always get the balance right. Yet other folks have proposed that having mild allergic reactions is an avoidance cue, telling us get away from a certain area. The big issue is that none of them have ironclad support, owing to the complexity of our immune system.

 

[OldChemE]

10 hours ago, mistermack said:

 

Some studies indicate that exposing babies to dirt etc actually primes their immune system in a healthy way, even if it intitially makes them a bit sick. Our ancestors evolved in Africa, living outdoors, and babies would be putting anything they picked up into their mouths, just as they do now. And the mother's wouldn't be stopping them, or taking much notice. It's a totally different start to life compared to today.

Love it!  I laugh because I come from a family of four boys, none of which have allergy issues.  Our mother, who had only a high school education, had 'funny' ideas for her time about allergies.  She encouraged all of us to play in the dirt as babies, and when one of us got a childhood disease she deliberately infected the other three.  We are all well into old age and still seem to have pretty good immune systems.

[Peterkin]

1 hour ago, OldChemE said:

She encouraged all of us to play in the dirt as babies, and when one of us got a childhood disease she deliberately infected the other three.

That was also common practice when I was very young. The thinking went: They're all going to catch it anyway; we'll have to nurse them through it; let's get it over with in one big mess instead of three or four little messes with the added burden of trying to isolate a sick child in a house already not big enough for all the people who live in it, and then they'll all be immune and we'll never have to deal with this again.

Nobody's mentioned vaccines. How odd!  

[Ken Fabian]

I would expect susceptibility to the more dangerous allergic responses have been weeded out by natural selection; we are descended from those that didn't die young from them. As medical intervention has become more capable and widely available it is more likely that genetic vulnerability is being passed along, which will be okay so long as the ability to provide medical care is sustained. Seems like increasing genetic variability is occurring but the natural selection part is being held at bay for a time.

Some good points from others - we are more likely to face exposure to substances that we haven't encountered before and immune responses can be strengthened or weakened by exposure or lack of it during childhood, apart from genetic vulnerability. We are better at identifying the culprits as well, modifying our food choices and exposure to allergens to avoid problems.

[mistermack]

The OP question is interesting though. Why doesn't evolution weed out all disorders? Especially inherited ones. Take haemophilia as an example. What possible benefit can it bestow on sufferers, so that it survived the evolutionary process? Wikipedia has a whole page on the variations and ramifications of haemophilia. So evolution certainly doesn't produce perfection. 

The workings of animals is so incredibly complicated that it's likely that every disorder has a different root, so there's no overall answer. Evolution only needs one human to produce one successful offspring, to keep the numbers up. So even with our low reproduction rate, there's room for a lot of wastage. And it's the wastage that drives evolution. 

Sometimes it's just down to luck. Your parents had certain genes that when combined, gave problems. It could be a one in fifty thousand chance. Other times, it's exacerbated by a bit of inbreeding, maybe several generations ago. Like the way that the royal families of Europe inflicted many of it's members with haemophilia B. Or Ashkenazi jews have a high incidence of haemophilia C. 

From an evolutionary point of view, rare occurrences don't kill enough individuals to wipe out the tendency in the general population.

I remember reading somewhere that the small percentage of Neanderthal dna that non-African people have are thought to cause quite a lot of inherited disorders, that Europeans and Asians get, that Sub-Saharan Africans don't. 

Other times, something that helps you fight one thing, can cause disorders of a different kind. Like sickle cell trait, in Africans, that helps fight malaria, but causes a debilitating illness in some. So in some areas it might be an overall benefit, because of high malaria, but in others, it's an evolutionary drag on the population.

So it's really so complicated that one simple rule doesn't apply to all.

 

[iNow]

4 hours ago, mistermack said:

Why doesn't evolution weed out all disorders?

Because not every disorder prevents you from successfully having offspring. 

[mistermack]

2 hours ago, iNow said:

Because not every disorder prevents you from successfully having offspring. 

It doesn't really work that way though. It might not prevent you  from successfully having offspring, but if it prevents one in ten, then it's a factor in evolution. It's really a numbers game at population level, which is where evolution happens. 

[Peterkin]

20 minutes ago, mistermack said:

It might not prevent you  from successfully having offspring, but if it prevents one in ten, then it's a factor in evolution. It's really a numbers game at population level, which is where evolution happens. 

If it only prevents one in ten successful offspring, it would take a very long time to disappear. Over that period, any number of natural catastrophes, plagues and wars may have decimated the population, so that it's impossible to tell which factor accounts for which 10% loss. 

 Some - the more serious - genetic anomalies do get bred out. How long it takes depends on how much human interference there is in the process: whether a society exposes its defective infants or saves them at all cost; whether the anomaly is prevalent in a class that gets more or less protection; whether intermarriage of castes and clans is encouraged or forbidden; whether birth control and reproductive choice of are practiced, etc.

 Some harmful genetic anomalies do not present until later in life, when reproduction has already taken, often without the carrier being aware that he or she has already passed it on. Hence DNA testing before a planned conception. 

Some uncomfortable but not disabling anomalies may be associated with traits that are valued by a culture.

Domestic evolution is subject to many of the same, but also some very different influences from natural evolution.    

Edited August 8, 2022 by Peterkin

[iNow]

35 minutes ago, mistermack said:

It doesn't really work that way though. It might not prevent you  from successfully having offspring, but if it prevents one in ten, then it's a factor in evolution.

I didn’t say it’s not a factor, but if 90% or more of the population is successfully breeding despite having the trait, then the evolutionary pressures asserted by that trait are minimal to nonexistent. 

Evolution selects only for the things which prevent breeding. Some people have extremely severe allergies, but they can still for the most part fornicate and sire offspring… and it’s FAR fewer than 1 in 10 who cannot… more like 1 in a few hundred thousand.

[TheVat]

So many allergies seem to be a mix of genetic and environmental factors.  Many have been largely latent in humans during 99% of human history because the genes involved were not activated by environmental toxins or dietary choices or modern forms of sequestering children from the dirtosphere.  Not clear there's been enough time for significant selection (and modern medicine, e.g. accurate tests for coeliac followed by gluten-free diet options, has largely eliminated selective pressure).  And how many women say, "I was going to marry Fred and have babies with him, but then I learned he eats gluten-free.  Never mind that he's handsome, strong, and smart, my man has to eat wheat!"    

If the genes for coeliac expressed consistently, and we were living in an agrarian society utterly dependent on the wheat harvest with no other carb options, then yes they would probably decrease in frequency under real selective pressure as the coeliacs would experience chronic IBS, poor absorption, intestinal lesions and failure to thrive such that they were skipped over as marital prospects.   But that sort of society was probably rare, and now nearly nonexistent.  There's almost always other options at the market, even in developing nations - millet, rice, cassava, etc.  

[mistermack]

1 hour ago, iNow said:

Some people have extremely severe allergies, but they can still for the most part fornicate and sire offspring… and it’s FAR fewer than 1 in 10 who cannot… more like 1 in a few hundred thousand.

Yeh, but what happens today, and what happened in the past are two very different things. This thread is really concerned with evolution long ago in the past. What kind of direction evolution is taking today is really worth a thread on it's own. But the genes that we carry today were selected for long ago in very different circumstances. 

In times of famine in the past, having an allergy might cost you your life, whereas today, you are just told what to avoid. 

A lot of evolution happened under times of severe stress, when for example, a few birds eggs or nuts might make the difference between life and death. 

[Peterkin]

57 minutes ago, mistermack said:

Yeh, but what happens today, and what happened in the past are two very different things.

How long a past are you considering? Within the last 6000 or so years, human selection has been no more natural than the breeding of livestock, and the environment in which humans lived was no more natural than their diets and lifestyles.

 

57 minutes ago, mistermack said:

But the genes that we carry today were selected for long ago in very different circumstances. 

And they're still complicated, and still responding to changing environmental factors. But the gene pools have also been remixed a number of time, on quite large scales, during that period. What was 'selected-for' in equatorial  Africa 60,000 years ago is not the same as the traits selected-for in northern Asia in the same period. But the resulting populations, and their counterparts in Europe and Oceania, have met in various capacities since that time, exchanging DNA all over the place. 

 

57 minutes ago, mistermack said:

In times of famine in the past, having an allergy might cost you your life, whereas today, you are just told what to avoid. 

No; people are still dying in famines. The wealthy populations with unfettered choice in their diet actually make up a relative insignificant portion of the human genome, though they probably account the majority of allergies, though data is obviously easier to collect in some places than other. And the number, especially of food allergies, is rising steadily.   https://comfyliving.net/allergy-statistics/

 

57 minutes ago, mistermack said:

A lot of evolution happened under times of severe stress, when for example, a few birds eggs or nuts might make the difference between life and death. 

And a lot more successful reproduction (i.e. offspring surviving to reproductive age) happened during times of relative plenty. Neither situation triggered a change in people's reproductive choices or behaviours - just more people died or fewer people died. 

Edited August 8, 2022 by Peterkin

[MigL]

We seem to be discussing two different issues.

In one case a substance is injested/absorbed/inhaled that produces a type of response which harms the system, and causes inflammation or outright cell/system death. It is a 'poison' to the cells/system.

In the other case, you have essentially a harmless substance, that is injested/absorbed/inhaled, and which causes an unwanted over-reaction by the immune system. Typical would be pollen and the overproduction of hystamines by the system.

( some, like bee stings, would involve both reactions )

Edited August 8, 2022 by MigL

[TheVat]

Looking at the OP, seems to be asking about the first category, conditions like peanut allergies where the person carries an Epi pen, and can go into anaphylaxis from even a small exposure.  Seems to be an interplay of genes and epigenetic effects.

https://www.sciencedaily.com/releases/2015/02/150224112917.htm#:~:text=This study suggests that the,allergy%2C and researchers wondered why.

I would speculate that the alleles that predispose toward serious peanut allergy is higher in Old World peoples, since they have only encountered peanuts since Spanish explorers brought them back from South America (where they were native, and long cultivated, and likely some selective pressure had time to work there).  

I note that the allergy is lower in developing countries generally, and one theory on that involves the hygiene hypothesis, alluded to here already.  In westernized nations most insulated from the natural environment, the rates are much higher.  

 

 

[CharonY]

39 minutes ago, TheVat said:

Looking at the OP, seems to be asking about the first category, conditions like peanut allergies where the person carries an Epi pen, and can go into anaphylaxis from even a small exposure.  Seems to be an interplay of genes and epigenetic effects.

https://www.sciencedaily.com/releases/2015/02/150224112917.htm#:~:text=This study suggests that the,allergy%2C and researchers wondered why.

I would speculate that the alleles that predispose toward serious peanut allergy is higher in Old World peoples, since they have only encountered peanuts since Spanish explorers brought them back from South America (where they were native, and long cultivated, and likely some selective pressure had time to work there).  

I note that the allergy is lower in developing countries generally, and one theory on that involves the hygiene hypothesis, alluded to here already.  In westernized nations most insulated from the natural environment, the rates are much higher.  

 

 

There are also competing hypotheses regarding exposure. There are studies (e.g. the LEAP-On study) which showed that exposure to certain allergens can reduce allergic reactions. It has been embedded in the toxin hypothesis to some degree. I.e. the allergic pathways are necessary to deal with harmful substances and indeed, many allergenic proteins in peanuts have defensive properties which work against certain bacteria and fungi. Based on bee venom studies it was found that these allergic pathways are also the same that are involved in developing resistance against toxic substances in general. While it is not clear under which conditions this detoxification pathways overreact (i.e. result in a harmful response) the fact that low-dose exposure seems in many (but not all) cases reduce the response might be just a built-in flaw in the way our immune system works.

Similarly this is why with certain pathogens we only get mild symptoms while it tries to eliminate them, whereas certain pathogens in certain individuals can cause severe immune reactions (e.g. cytokine storms). It is an imperfect system to begin with and a lot of factors, environmental and genetic, influence the overall outcome.

2 hours ago, MigL said:

We seem to be discussing two different issues.

In one case a substance is injested/absorbed/inhaled that produces a type of response which harms the system, and causes inflammation or outright cell/system death. It is a 'poison' to the cells/system.

In the other case, you have essentially a harmless substance, that is injested/absorbed/inhaled, and which causes an unwanted over-reaction by the immune system. Typical would be pollen and the overproduction of hystamines by the system.

( some, like bee stings, would involve both reactions )

As I tried to allude to above, the distinction between those are not necessarily clear. Non-cytotoxic substances can cause inflammation, sometimes even severe ones. Sometimes it makes sense, non-toxic bacterial proteins or other components could be used as recognition for foreign substances that need to be addressed, for example. In others it is simply not clear. But then, a system that is capable of identifying and dealing with new substances is almost by default less categorical. That is, the system has to learn how to react. As such there is always the risk that the response is not ideal relative to the risk of the exposure in the first place. 

[mistermack]

On 8/8/2022 at 7:53 PM, Peterkin said:

How long a past are you considering? Within the last 6000 or so years, human selection has been no more natural than the breeding of livestock, and the environment in which humans lived was no more natural than their diets and lifestyles.

 

I would pretty much disregard the last 6,000 years when considering our current genetic makeup. With a long-lived slow reproducing animal like humans, it's not really long enough to have produced much change. The only thing that has happened that might make a difference is the greater mobility of the current era, producing more rapid and widespread mixing of genes than was historically happening. Usually that's a good thing, avoiding inbreeding problems, but it can introduce problems if you are breeding with people like Neanderthals, who's genes are reckoned to produce some genetic problems in Europeans and Asians.

I was wondering if breast feeding has been tested for an effect on allergies. I seem to remember some speculation or indications that breast-fed people suffered less from allergy problems. Maybe nuts and eggs etc eaten by a mother might prime the babies immune systems through the milk. 

[Peterkin]

2 hours ago, mistermack said:

I would pretty much disregard the last 6,000 years when considering our current genetic makeup.

I believe that would be a mistake. The last 6000 years accounts for the most intense human intervention in human reproductive process, the most rapid mixing of gene-pools, drastic changes in diet and habitat, and introduction of new elements into the environment.

2 hours ago, mistermack said:

I was wondering if breast feeding has been tested for an effect on allergies.

It has been studied extensively, with complicated and as yet unresolved conclusions. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145659/

[Ken Fabian]

On 8/9/2022 at 2:00 AM, mistermack said:

It doesn't really work that way though. It might not prevent you  from successfully having offspring, but if it prevents one in ten, then it's a factor in evolution. It's really a numbers game at population level, which is where evolution happens. 

 

On 8/9/2022 at 2:39 AM, iNow said:

I didn’t say it’s not a factor, but if 90% or more of the population is successfully breeding despite having the trait, then the evolutionary pressures asserted by that trait are minimal to nonexistent. 

I think Mistermack has it right. I think it would make a significant difference to overall reproductive success - not necessarily to the birth rate but the group ability to support itself and provide well for the ones that are born. A prevalence of even low grade allergies will impact the group's success.