Lactase Persistence Over the Last 3,000 Years

[Anfänger]

Genomic Data from an Ancient European Battlefield Indicates On-Going Strong Selection on a Genomic Region Associated with Lactase Persistence Over the Last 3,000 Years


Abstract

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235*T (Enattah et al. 2008), only rose to appreciable frequencies during the Bronze and Iron Ages (Mathieson et al 2015; Olalde et al. 2018), long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of peoples from the Pontic-Caspian steppe that began around 5,000 years ago (Allentoft et al. 2015; Furholt et al. 2016). We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (~3,200 BP); the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (~4,100 to ~3,700 BP) and 37 individuals from eastern Europe and the Pontic-Caspian Steppe region, predating both Bronze Age sites (~5,980 to ~4,250 BP). We infer low LP in all three regions, i.e. in northern Germany, south- eastern, and eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06, and conclude that the selection was on-going in various parts of Europe over the last 3,000 years.

https://papers.ssrn.com/sol3/papers....act_id=3565013

[Angela]

Thanks, Anfanger.

It's as some of us have been saying for years. Lack of the allele didn't prevent people from Anatolia and "Old Europe" from consuming dairy products, and the people of the Pontic Caspian steppe didn't bring it to Europe, just as they did not bring light pigmentation to Europe.

So, hopefully all these disproved ideas will go into the dust bin.

Interesting also the line about the Tollennsee remains: Genetic data indicate that these individuals represent a single unstructured Central/Northern European population.


I have to read the paper to see if it was a representative sample, however.

[ratchet_fan]

Thanks, Anfanger.

It's as some of us have been saying for years. Lack of the allele didn't prevent people from Anatolia and "Old Europe" from consuming dairy products, and the people of the Pontic Caspian steppe didn't bring it to Europe, just as they did not bring light pigmentation to Europe.

So, hopefully all these disproved ideas will go into the dust bin.

Interesting also the line about the Tollennsee remains: Genetic data indicate that these individuals represent a single unstructured Central/Northern European population.


I have to read the paper to see if it was a representative sample, however.

Maybe you don't need LP alleles to consume dairy (minus actual milk).

[Angela]

Maybe you don't need LP alleles to consume dairy (minus actual milk).

It depends on the product to some extent. Hard cheeses like, say, parmigiano reggiano, are easy on the digestive system because they have less lactose. Soft cheeses have more. Natural yogurts are also easier to digest.

However, I've also come to believe that the gut biome has a big impact on the ability to digest lactose. We don't eat the same kinds of foods that our ancestors ate. Even the strains of wheat have been modified. So, our ancestors might have had less of a problem consuming cheeses and yogurts.

However, I do think there's a reason that some Southern European populations, like Italians, have never adopted the custom of "drinking" milk with their meals. The only place I ever heard of it in Italy was up in the Apennines, but dairy products are half their calories, and even there it wasn't with meals, but more something the children might drink. Anyone who couldn't digest lactose up there would have died after weaning: it was dairy, polenta or cornmeal mush, a little wheat, some fish and a bit of meat, primarily game and pork products, and the odd chicken. Selection in action.

Where I was raised it was considered disgusting. Heck, I considered it disgusting when I saw my friends drinking it; usually with a peanut butter and jelly sandwich made with "white" bread. Yuck. I was only partly converted when I started dunking oreos in a cup of milk, but I still would never dream of drinking it with actual food. Childhood habits die hard. I had to constantly remind myself to put "butter" out for the bread if Americans were coming for dinner too. :) Oh, I did eventually become a bit fond of peanut butter and jelly sandwiches too. You can get used to anything given long enough I suppose.

[ratchet_fan]

It depends on the product to some extent. Hard cheeses like, say, parmigiano reggiano, are easy on the digestive system because they have less lactose. Soft cheeses have more. Natural yogurts are also easier to digest.

However, I've also come to believe that the gut biome has a big impact on the ability to digest lactose. We don't eat the same kinds of foods that our ancestors ate. Even the strains of wheat have been modified. So, our ancestors might have had less of a problem consuming cheeses and yogurts.

However, I do think there's a reason that some Southern European populations, like Italians, have never adopted the custom of "drinking" milk with their meals. The only place I ever heard of it in Italy was up in the Apennines, but dairy products are half their calories, and even there it wasn't with meals, but more something the children might drink. Anyone who couldn't digest lactose up there would have died after weaning: it was dairy, polenta or cornmeal mush, a little wheat, some fish and a bit of meat, primarily game and pork products, and the odd chicken. Selection in action.

Where I was raised it was considered disgusting. Heck, I considered it disgusting when I saw my friends drinking it; usually with a peanut butter and jelly sandwich made with "white" bread. Yuck. I was only partly converted when I started dunking oreos in a cup of milk, but I still would never dream of drinking it with actual food. Childhood habits die hard. I had to constantly remind myself to put "butter" out for the bread if Americans were coming for dinner too. :) Oh, I did eventually become a bit fond of peanut butter and jelly sandwiches too. You can get used to anything given long enough I suppose.

Is yogurt a big thing in Europe besides the Balkans and Greece? I also wonder if that is a recent product or if it dates back to the Neolithic. I imagine most dairy consumption was just cheese in the Neolithic. I could be wrong.

Milk with meals is pretty disgusting imo. I've heard of people having milk with lunch or dinner but still disgusts me. Actually come to think of it, the school lunches growing up had milk. I don't think I consumed it once. Milk doesn't mix with meat, bread or veggies imo.

I'm like you. I only like milk with Oreos or a nice piece of chocolate cake. I have no trouble digesting it but still don't like it.

Milkshakes and egg creams on the other hand...

[Dimanto Ruben]

It depends on the product to some extent. Hard cheeses like, say, parmigiano reggiano, are easy on the digestive system because they have less lactose. Soft cheeses have more. Natural yogurts are also easier to digest.

However, I've also come to believe that the gut biome has a big impact on the ability to digest lactose. We don't eat the same kinds of foods that our ancestors ate. Even the strains of wheat have been modified. So, our ancestors might have had less of a problem consuming cheeses and yogurts.

However, I do think there's a reason that some Southern European populations, like Italians, have never adopted the custom of "drinking" milk with their meals. The only place I ever heard of it in Italy was up in the Apennines, but dairy products are half their calories, and even there it wasn't with meals, but more something the children might drink. Anyone who couldn't digest lactose up there would have died after weaning: it was dairy, polenta or cornmeal mush, a little wheat, some fish and a bit of meat, primarily game and pork products, and the odd chicken. Selection in action.

Where I was raised it was considered disgusting. Heck, I considered it disgusting when I saw my friends drinking it; usually with a peanut butter and jelly sandwich made with "white" bread. Yuck. I was only partly converted when I started dunking oreos in a cup of milk, but I still would never dream of drinking it with actual food. Childhood habits die hard. I had to constantly remind myself to put "butter" out for the bread if Americans were coming for dinner too. :) Oh, I did eventually become a bit fond of peanut butter and jelly sandwiches too. You can get used to anything given long enough I suppose.

Yes, I agree. I grew up in the Netherlands and my Dutch mom usually gave us milk together with the meal and I never liked it and it never really felt quite ''right'' for my stomach. I abolished it as soon as I began preparing meals for my self. I feel we have somewhat different digestive systems, as we're completely different in what we like to eat. I have a good comparison with my half-brother who is fully North Dutch and we're very, very different in terms of what and how we prefer to eat. You mentioned ''Italy'' as if Italy is one population, while it's a known fact, the Mezzogiorno is significantly different genetically speaking (N_Italy historically had a high calorie, animal fat based diet) and that certain diseases are more prevalent in the North than in the South because of this divergence. I believe a recent study was published in relation to Covid-2 susceptibility in both Northern and Southern Italian populations, the latter being less prone of developing harsh symptoms and even death.
I also like peanut butter on a sandwich though, but let's admit it's quite tasty!

[Angela]

I'm perfectly aware that there is a lot of variation in Italy, but the average for lactase persistence is pretty low overall, or to put it another way, lactase non-persistence is pretty high.

Interestingly enough, it doesn't follow the typical smooth north/south cline.

As always I believe it varies with the foods easily grown in the area. Many places in the north practice dairy farming. Dairy farmers would tend to score a little higher for lactase persistence, I would think, although the numbers indicate that the majority still don't carry the derived allele, hence, perhaps the fact that even in the north people don't go around chugging big glasses of milk.

Likewise, in the south, in places like Campania they make a lot of soft cheese, so perhaps that would explain their scores.

The center has the lowest levels. Makes sense to me. Liguria is not really the center, but I would bet the levels for lactase persistence are low. There is no pasturage for cows; the cheese usually produced is hard pecorino cheese, and the diet is very centered on fish, olive oil, bread and grapes. Certainly, no one would dream of drinking milk.

Abstract

Background: Adult-type hypolactasia is a frequent condition of lactose malabsorption; in Europe the distribution of adult-type hypolactasia have been shown to display a North-South gradient. Genotyping for LCT-13910 C>T polymorphism has been proposed as a useful diagnostic marker of adult-type hypolactasia. Data concerning lactase non-persistent genotype distribution in Italy are confused and not well characterized. The aim of this study was to determine the prevalence of CC-genotype corresponding to lactase non-persistence in Italian population.
Methods: We genotyped 1312 adult Italian subjects for LCT-13910 C>T polymorphism by KASPar chemistry (KBioscience Ltd., Hoddesdon, England, UK).
Results: The frequency of the lactase non-persistence genotype of our sample was 62.3% that was higher than the values published for adult hypolactasia in Italy. In our study a frequency of 58.6%, 74.1% and 67.1% was detected in the three main macro-regions of Italy (North, Center, and South), respectively.
Conclusions: For the first time we analyzed the distribution of the LCT-13910 CC genotype in a big population of Italian subjects. Our data did not validate the presence of a North-South gradient for adult hypolactasia along the Italian peninsula."


Lactase non-persistent genotype distribution in Italy

Cristina Zadro 1, Savina Dipresa 2, Giovanni Zorzetti 2, Annalisa Pediroda 2, Francesco Menegoni 2


Given the legendary long life and good health of Italians, it should be clear you don't need to consume tons of dairy products to be healthy. A little bit will do you.

[Dimanto Ruben]

I'm perfectly aware that there is a lot of variation in Italy, but the average for lactase persistence is pretty low overall, or to put it another way, lactase non-persistence is pretty high.

Interestingly enough, it doesn't follow the typical smooth north/south cline.

As always I believe it varies with the foods easily grown in the area. Many places in the north practice dairy farming. Dairy farmers would tend to score a little higher for lactase persistence, I would think, although the numbers indicate that the majority still don't carry the derived allele, hence, perhaps the fact that even in the north people don't go around chugging big glasses of milk.

Likewise, in the south, in places like Campania they make a lot of soft cheese, so perhaps that would explain their scores.

The center has the lowest levels. Makes sense to me. Liguria is not really the center, but I would bet the levels for lactase persistence are low. There is no pasturage for cows; the cheese usually produced is hard pecorino cheese, and the diet is very centered on fish, olive oil, bread and grapes. Certainly, no one would dream of drinking milk.

Abstract

Background: Adult-type hypolactasia is a frequent condition of lactose malabsorption; in Europe the distribution of adult-type hypolactasia have been shown to display a North-South gradient. Genotyping for LCT-13910 C>T polymorphism has been proposed as a useful diagnostic marker of adult-type hypolactasia. Data concerning lactase non-persistent genotype distribution in Italy are confused and not well characterized. The aim of this study was to determine the prevalence of CC-genotype corresponding to lactase non-persistence in Italian population.
Methods: We genotyped 1312 adult Italian subjects for LCT-13910 C>T polymorphism by KASPar chemistry (KBioscience Ltd., Hoddesdon, England, UK).
Results: The frequency of the lactase non-persistence genotype of our sample was 62.3% that was higher than the values published for adult hypolactasia in Italy. In our study a frequency of 58.6%, 74.1% and 67.1% was detected in the three main macro-regions of Italy (North, Center, and South), respectively.
Conclusions: For the first time we analyzed the distribution of the LCT-13910 CC genotype in a big population of Italian subjects. Our data did not validate the presence of a North-South gradient for adult hypolactasia along the Italian peninsula."


Lactase non-persistent genotype distribution in Italy

Cristina Zadro 1, Savina Dipresa 2, Giovanni Zorzetti 2, Annalisa Pediroda 2, Francesco Menegoni 2


Given the legendary long life and good health of Italians, it should be clear you don't need to consume tons of dairy products to be healthy. A little bit will do you.

Yes, I think you're making sense (given the conclusion from the citation) though there's lots of overlap between regions and extensive trade of dairy products from one area to another. Only in desolate valleys a theory like this would work and even though we Italians were quite attached (or rather dependable) to our hometown and area, movements from region to region did occur over the centuries which is detectable DNA-wise. I see my own eating habits as an experiment when comparing to my Dutch relatives and it's quite interesting that we in fact are different in what type of diet we feel most comfortable with. I tend to do much better on pasta than potatoes, which in the latter case is consumed significantly in the Netherlands. The same goes for fish and meat; I prefer fish over meat while my Dutch family are more attracted towards meat (apart from the veggies )

[Angela]

Well, you wouldn't do very well in my parts of Italy; we eat tons of potatoes and meat.

[Dimanto Ruben]

Well, you wouldn't do very well in my parts of Italy; we eat tons of potatoes and meat.

I do like gnocchi though, but my stomach likes pasta much better! And we eat mostly seafood and other types of fish for generations, so it makes sense I digest fish better. Not sure which alleles I've inherited from either side which could cause these differences in digestion, but it seems my phenotype and digestion system is largely Southern Italian as well as my taste for quality food and sense of style!!

[halfalp]

The real question is, how do you understand intolerance as a self, and especially in prehistoric times. For exemple myself, Gluten-like food, especially Barilla pasta give me gastric problems maybe 80% of the time when i eat them ( how to live without pasta and bread? ). But really, in a day-to-day life, without internet, those problems i wouldn't think of them that much.

So when you live in prehistoric times, in a village, how do you consider a diarrhea? Do you immediately stop eating the questioning food? or do you let it go?

I think it's interesting to link certain mutation to tolerate some kind of food. But human adaptation capabilities goes over mutations. In the contexte of Old Europe, or Chalcolithic Steppe, how do we know if the consumptions was linked to an adaptation through a gene, or was it just human willpower?

The gene to tolerate gluten or dairy probably didn't change that much the " mentality " of eating such food through the eras.

[Philjames100]

Distribution of the lactase persistence allele 13910*T (rs4988235*T):



https://link.springer.com/article/10...439-017-1847-y



The spread into Africa is associated with R1b-V88, and possibly T1a.

[Angela]

Distribution of the lactase persistence allele 13910*T (rs4988235*T):



https://link.springer.com/article/10...439-017-1847-y



The spread into Africa is associated with R1b-V88, and possibly T1a.

Actually, although some of the "European" variety of lactase persistence did make it into Africa, it is not the only variety.

There are at least two and perhaps three African specific versions, i.e. they arose in Africa or more likely in Arabia through selection.

So, no, it's not a European "specific" trait. All the skinheads can stop having "milk drinking" rituals, unless they want to invite some Kenyans to the party, for example. :)

There are numerous papers on the subject. Just use google.

This is to get you started.
https://bmcresnotes.biomedcentral.co...833-1/tables/2

I have no idea how you know V88 is responsible for bringing to Africa, but even if it did, its carriers would have developed the trait in their long journey as males of a herding culture. Certainly mesolithic Europeans were "not" lactase persistent. It's a relatively recent trait all over the world.

[Angela]

The real question is, how do you understand intolerance as a self, and especially in prehistoric times. For exemple myself, Gluten-like food, especially Barilla pasta give me gastric problems maybe 80% of the time when i eat them ( how to live without pasta and bread? ). But really, in a day-to-day life, without internet, those problems i wouldn't think of them that much.

So when you live in prehistoric times, in a village, how do you consider a diarrhea? Do you immediately stop eating the questioning food? or do you let it go?

I think it's interesting to link certain mutation to tolerate some kind of food. But human adaptation capabilities goes over mutations. In the contexte of Old Europe, or Chalcolithic Steppe, how do we know if the consumptions was linked to an adaptation through a gene, or was it just human willpower?

The gene to tolerate gluten or dairy probably didn't change that much the " mentality " of eating such food through the eras.

If you're saying, well, it wouldn't kill you, no, it probably wouldn't kill you directly. The problem is that in the past people lived on the knife edge of survival. Cheese, especially certain kinds of cheese, might not be a huge problem, although if it is causing evacuation you realize most of the nutrients are being lost as well? That could be made up if the group is living somewhere like Liguria, for example, where fish is available from sea and rivers, high fat oil from olives and high caloric wine is easily available, and crops (vegetables, some grain) can be harvested three times a year.

However, let's say that a group lives in an inland location with a harsh continental climate. You can grow only one crop a year. If the crop fails, or is just not opulent, and game isn't sufficient, these people depend on the dairy from their animals, including fresh milk. People without a single lactase persistent gene who consume lots and lots of dairy, and attempt to drink lots of milk can get violently, explosively ill, lose weight, develop inflamed, ulcerated colons etc. It is no joke.

So, I think, as I always have, that the trait spread where it came in handy. Where it wasn't as necessary, there wasn't as much selection for it.

There's a reason it's the herding cultures in Africa which have lactase persistence genes, not the almost strictly farming cultures.

[Philjames100]

it's not a European "specific" trait.

I didn't say it was. The paper you posted was about the specific lactase persistence allele 13910*T.

[Angela]

I didn't say it was. The paper you posted was about the specific lactase persistence allele 13910*T.

No need to be defensive.

It's just a statement of fact of which some people might not be aware.

Goodness, even smileys don't work?

[halfalp]

If you're saying, well, it wouldn't kill you, no, it probably wouldn't kill you directly. The problem is that in the past people lived on the knife edge of survival. Cheese, especially certain kinds of cheese, might not be a huge problem, although if it is causing evacuation you realize most of the nutrients are being lost as well? That could be made up if the group is living somewhere like Liguria, for example, where fish is available from sea and rivers, high fat oil from olives and high caloric wine is easily available, and crops (vegetables, some grain) can be harvested three times a year.

However, let's say that a group lives in an inland location with a harsh continental climate. You can grow only one crop a year. If the crop fails, or is just not opulent, and game isn't sufficient, these people depend on the dairy from their animals, including fresh milk. People without a single lactase persistent gene who consume lots and lots of dairy, and attempt to drink lots of milk can get violently, explosively ill, lose weight, develop inflamed, ulcerated colons etc. It is no joke.

So, I think, as I always have, that the trait spread where it came in handy. Where it wasn't as necessary, there wasn't as much selection for it.

There's a reason it's the herding cultures in Africa which have lactase persistence genes, not the almost strictly farming cultures.

I agree, intolerances makes you ill firstly with specific low-level symptoms, but can evolve in many different ways, including cancers, tumors, auto-immune diseases etc...

But especially in a survival contexte, because we dont know how all those ancient populations reacted to lactase or gluten for exemple, symptoms linked with gluten or dairy could be seen as " usual buisnesses ". And the transition between being sick and not and why, was not clear for them.

To be more explicit, i dont think symptoms of eating gluten or lactase by people who didn't tolerate them was as obvious as the symptoms you get from a cobra bait.

Therefore, i think we can easily be tricked by the fact that farmers or herders could have been huge crops ( gluten ) or dairy consumers without really being aware to how it harmed them because they didn't have lactase persistence. Wich also could have tricked us on the fact, that yamnaya ancestry clearly linked with herding culture, should have had those tolerances, but actually did not, or not much.

Especially in the contexte of Triticeae and Fabaceae, it's amazing how wide this culture spread, initially from the middle-east, then in all directions, maybe with already daily gastric symptoms.

Now, did the culture of dairy consumptions clearly peaked after a said population had the genes for lactase tolerance would be interesting to know.

[Philjames100]

No need to be defensive.

It's just a statement of fact of which some people might not be aware.

How am I being defensive? You said I claimed something which I didn't.

[Philjames100]

I have no idea how you know V88 is responsible for bringing to Africa

It's found in central/west African populations that have R1b-V88 and European ancestry.

[halfalp]

It's found in central/west African populations that have R1b-V88 and European ancestry.

Sounds speculative at last. The reality is that this tolerance probably became common in little groups of heavy daily consumers and propagated after. The story is probably not different in Scandinavia, West Africa and Indian Sub-Continent.

[ratchet_fan]

So where did 13910*T and the 22018*A arise?

I believe the distribution in African follows the spread of Chadic languages and R1b-V88 which is why I believe that assertion was made.

[Angela]

How am I being defensive? You said I claimed something which I didn't.

That was not the intent of my comment.

This is the second time I'm telling you that.

I know what I meant to say; you can only surmise.

Drop it.

[Salento]

So where did 13910*T and the 22018*A arise?
I believe the distribution in African follows the spread of Chadic languages and R1b-V88 which is why I believe that assertion was made.

... some T and R1* went Back to Africa:

... Luis et al. (2004) suggest that the presence of T on the African continent may, like R1* representatives, point to an older introduction from Asia ...

[Salento]

y T Haplogroup is understudied.
It seems that it isn’t worth the time, and there is no glory in studying a rare and widely spread Haplogroup.

so nobody knows for sure where it originated, where it went. And where it’s going :)

[Archetype0ne]

Hmm... to begin with the common symptoms of lactose intolerance are an inconvenience at best, big one today with the variety of calories we can consume, but I assume in the distant past it was a non factor.

Most Balkan people as well as Turks will have yogurt or cream with their wheat based Bureks and what not, and judging by the map of lactose persistence that is not indicative of the fact.

I checked lactose intolerance symptoms and I have them sometimes. I still eat icecream, have all types of soft and hard cheeses, love dhallë or airan with Burek, and my favourite Pizza is Quatro Formagi. From what I understand you can increase your threshold tolerance by just like... consuming lactose...

Still do not understand what the big deal is to necessitate such reactions.