The story of lactase persistence (“lactose tolerance”) evolving is one of the best gene-culture coevolution stories we had. Arguably it was the canonical example. The story was simple, multiple times humans took up dairy-culture, and multiple times humans changed so that they could digest lactose, milk sugar, into adulthood. This is about 30% of the caloric intake of raw milk (the rest being fat and protein). For some people their gut flora reacts negatively to the sugar bath if it’s not digested, leading to discomfort in addition to wasted calories.
In the 2000’s several mutations were discovered around LCT, the gene responsible for producing lactase, which breaks down lactose. One mutation was found across Europe and Central Asia. Another among the Arabs. And Another in East Africa. The “mutational target” was big. The mutation in the European and Central Asian variant breaks a regulatory element that represses the expression of LCT in adults. There are lots of ways to break something. Lactase persistence isn’t really a gain of function, it’s just never shutting off the function, which itself is a feature, not a bug.
The haplotype around LCT is long and indicative of a really strong sweep in Europeans. It was in some ways a positive control for tests of selection.
The problem is that there are now major problems with this narrative. In short, dairy-culture predates the increase in frequency for lactase persistence alleles by thousands of years. The ancient DNA transects in Europe are so good that it seems pretty clear that the frequency was way lower during the Iron Age, and didn’t reach “modern” levels until the historical period.
The same is now known to be true in Africa: Humans were drinking milk before they could digest it.
This doesn’t mean that these mutations have nothing to do with milk. But there needs to be a rethink of the selection story. Perhaps there was a genetic modifier that spread recently which isn’t a big mutational target, and that’s why the lactose digestion alleles rose in the last 3,000 years? I don’t know. No one really does.
Somewhat misleading – they were digesting milk products not raw milk – but those who could digest raw milk got a significant advantage
Yes, any fermentation that got rid of the lactose would suffice, cheese, alcohol… And some processing that reduced or eliminated the lactose like butter making would work, too.
Lactose tolerance was selected recently, and I am somewhat curious about where it originated. From there it would have randomly passed along for thousands and thousands of years before being selected for for whatever reason. We cannot know for sure but we can look for the earliest occurrence. Razib, which is the earliest sample you are aware of to have the European lactose tolerance variant? I have heard a while back that a French WHG (not from any of the recent 2019 and 2020 papers) had it but I don’t know if that claim was true.
Part of the cool thing about looking a parallel lactase selection stories is that we can develop a good working hypothesis for reasons.
Like, per Mathiesons latest on the topic, increases in frequency due to selection happen in at least Iberia, England (Central Europe certainly too) in different time frames, and apparently not at all in Italy (maybe partly a a function of turnover in ancestry in Italy, lots of Aegean, Levant). So what changed in each region, that we can see in archaeology and bioarch, in each time frame? What consistent co-selected traits do we see, if any?
Extending into Africa, Arabia and the broader South Asian region adds robusticity. Stronger than looking at one region in isolation.
I was interested by a suggestion by one author on this topic that milk may have mattered to provide a separate fresh water source that had less pathogen load than other sources, and then that might make digestion matter more. Cows as early water treatment… No idea if that’s actually plausible though.
Is anyone looking at it from the other side? There probably is an advantage to lactase impersistence, if just to avoid the cost of producing it, but maybe to stop older siblings from taking the milk intended for the younger ones. The cost may have lowered with time, as people had more resources, and the benefits of persistence may have grown as dairy availability grew.
Also, I see here a point that evolution is stochastic, works in fits and starts and not always goes where you would expect it.
@Ezequiel, hard to know how you could even look at that questions; there are no human populations we know of where their ancestors were LP and then the descendents are nLP.
I would suspect that we’d find that the nLP ancestral state just arose because adult LP wasn’t any selective advantage at all in the ancestral environment, so mutations that dinged up adult LP had no fitness cost.
(Like for the specific example, I don’t think human ancestors would have major problems with extended weaning that would create selective pressure for the nLP trait – as far as we can tell LP populations both don’t have extended weaning, and that doesn’t explain adult LP?).
There may be an nLP advantage as well, but I would still guess the selective coefficient is probably very small and I doubt we’d see any much change over even hundreds of thousands of… Unless there’s some pleitropy potential?
The real question may be, what made these people switch from fermentation to drinking high-lactose unfermented milk. Perhaps a cultural practice, maybe a shibboleth-like tradition separating the herders from their neighbors? Perhaps a transition from wide-area herding, where most cows were so far away from most people that anything other than fermentation was simply impractical, to grazing the cattle near the village, with the cows now returning to the family sheds for the night, making fresh milk readily available to all villagers?
As others have pointed out, the title is slightly misleading
Everyone can benefit from the fats & proteins in milk
But it is only the young/youth who can benefit from the carbs to varying degrees
My guess is that the benefits of the fat/protein would have compensated for the IBD caused by the carbs, & eventually some kind of low level tolerance would have set in.
So some Africans would have been able to tolerate the carbs but not digest it
I have trouble believing that many adults drank milk before the 20th century and the invention of mechanical refrigeration. My guess is that in those conditions almost all milk production was used to make butter and cheese, which can be preserved for long periods of time and which are far more transportable than fluid milk.
Natural fermentation -> yoghurt, and kefir (no lactose).
Advantage in weaning children from human milk to animal milk, so there is milk for the next baby, so increased reproduction. And young children are still lactase persistent, so it goes from there – regular milk consumption will actually cause lactase persistence to extend for longer.
So adults continue to be lactose intolerant, but children who are lactose tolerant are getting older and older, and then finally it continues into adulthood. But if you don’t use it, you lose it.
regular milk consumption will actually cause lactase persistence to extend for longer.
I would think that any bout of severe diarrhea has a strong potential to interrupt anyone’s milk consumption (and perhaps to upset the gut microflora too). And it surely was more common in the past, with its hygiene and potable water problems. So I would assume that it was relatively common for people to lose microbiotic tolerance to lactose, either permanently or for long stretches, even in their childhood.
I meant it will cause lactase persistence to extend longer in childhood.
People make generalisations that they shouldn’t make. My wife is northern Han (and not north-western – east coastal, and yes, she’s been genotyped) – she can drink a big glass of milk without any problems at all, and does so regularly to get the calcium. She never had milk to drink as a child. I doubt she can digest the lactase, but she gets all of the other good stuff. Never gets diarrhoea, gut cramps or any of that.
On the topic of “other good stuff”, I wonder if ancient dna co-analysis of ruminant genomes has anything to offer here? How did their milk yield and composition change?
Maybe it doesn’t matter if you can’t digest lactose as much if your Ruminant Breed Of Choice is much more all in on producing lipids, but does matter if you focus on high milk sugar breeds? Speculative though as I don’t know that there’s enough understanding of whether strong selection even happened in ruminants for these traits in prehistoric eras.
I also wonder if this interacts with FADS1 selection at all; we kind of know that there was a shift in lipid metabolism there from animal->vegetable fats. Maybe you then change the selective vector of what you are trying to get out of milk? That doesn’t seem very relevant to pastoralists though, so maybe it’s wrong.
Maybe the target wasn’t human nutrition, but the microbiome itself.
@Matt
Since Razib hasn’t chimed in will ask you. What is the oldest sample with the European lactose persistence variant that you are aware of?
@Dathang, I’ll be honest, I can’t remember any specific sample. It would be great to have some curated list by allele status but nope.
The paper https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000742 claims it was the supposed Sredny Stog II sample in Ukraine (the much hyped earliest R1a Z93), but as Reich lab (and Davidski) have recently confirmed that he is not Sredny Stog and misdated and just a MLBA steppe guy, it’s not him.
Aside from him there’s one other pre-3000 BCE samples in the Balkans in Iain Mathieson’s blog post, but this person be misdated too, as there have been lots of problems around sample dating – http://mathii.github.io/2019/10/12/the-spread-of-the-european-lactase-persistence-allele . Sample name not specified, apologies.
After that we find it in a broad swathe of North Europe + Western steppe at low frequency.
If you can, I’d suggest emailing Mathieson, tweeting him or leaving a comment on his latest paper on the topic on biorxiv ( https://www.biorxiv.org/content/10.1101/2020.11.17.387761v1.full) and see if he can get back to you?
It seems plausible enough to me that it was present in some low frequency in the steppe or EEF populations that led to later Corded Ware, but at pretty low frequency. Could have been anywhere though really! Maybe they could do some sort of haplotype/ LD analysis to really work it out (e.g. is the window around the allele enriched for EEF/steppe ancestry).
@DaThang
German Beaker I0112 (50.4% Yamnaya, 31.2% Barcin, 18.4% WHG in a basic model in Vahaduo) is dated to 2450-2140 BC from Mathieson et al. – Genome-wide patterns of selection in 230 ancient Eurasians.
Mathieson notes apparently earlier samples on the map in
https://mathii.github.io/2019/10/12/the-spread-of-the-european-lactase-persistence-allele
with caution: “Before 5000 BP, there are only a couple of occurrences of the allele. It’s quite possible that these are genotyping or dating errors.”
Curious which specific ones they are too because I don’t recall off the top of my head. The one in the Ukraine is probably I6561, whose dating is apparently insecure (originally Ukraine_Eneolithic, now Ukraine_MBA) and might actually be later than that Beaker one. The other one in Hungary, I’m not sure about but it might be Beaker-related and basically contemporary. I don’t remember any earlier ones personally.
Repeated some stuff due to the later appearance of Matt’s post, no disrespect to him. 😉
Hey, “Great minds think alike”!
Though, will add now, realized the paper “Why and when was lactase persistence selected for? Insights from Central Asian herders and ancient DNA” has a supplement file S1 Table with their oldest detected samples with LP allele (status=1), in the table. Though there is probably much more adna now than they use (they use about 1434 samples, while dated ancient samples in latest Reich lab file run to I believe about 5400).
Here’s a subset of that table listing samples detected with allele: https://imgur.com/a/My0PgI1
The earliest samples other than I6561, which is apparently probably later than initially believed (being labelled QUESTIONABLE Ukraine_MBA in latest Reich Lab anno file), are a bunch of Beakers and others at around 2300 BCE, then further others after (and obviously many more detected alleles as % of samples as we get into medieval period). Though this probably doesn’t mean anything particular about the Beaker folk and the allele (as much as many areas where the allele is frequent today are post Beaker) and probably just reflects that loads of big studies of Beakers had happened before this dataset was compiled. (You may notice some of the date codes for Latvia_BA are slightly awry in above image; it was like that in the table!).
They don’t seem to have identified any earlier sample from Hungary/Balkan (and I think forgetful is right that it is Hungary, I’m not as good at geography!) that was indicated by a dot as pre-3000 BCE in Iain Mathieson’s blog post.
Thank you both Matt and Forgetful. So it looks like the oldest known ones are from the bronze age and none from the mesolithic.
@Matt
Thanks for the ref. I have a feeling that other early sample is I2786, so our secure earliest are some Beaker, post Corded Ware and Unetice individuals around the same time. Steppe-related ancestry does seem to connect them, from NW Europe to South Asia (the much later Saidu_Sharif_H ones, at least) so it isn’t implausible to suggest it first arose in that kind of population.
An issue with that is that we still aren’t exactly sure how Corded Ware and Bell Beaker are connected (whether on the steppe or further west) and so whether this goes back to a general Steppe_EBA population or a more specific, as you note, EEF-mixed population that both Corded Ware and Bell Beaker would go back to under certain scenaria. If more plausibly Yamnaya connected individuals** also show it in the future, we might be able to directly pinpoint an origin further east and maybe earlier; though of course even Yamnaya seems to have a small amount of EEF-related ancestry. When the frequencies are apparently that low early on, you’d probably need a lot of samples though to more directly show it rather than use more indirect methods.
**Whether on the steppe or in more mixed form in the BA Balkans, if we assume the EEF-HG related ancestry in CW and BB to be different to the Balkan one, which it probably is at least in CW considering the early Baltic and Polish samples.
To be a bit clearer, since I also mentioned the early Baltic and Polish CW samples (that are Yamnaya-like with perhaps some extra HG) that would seem to contradict the “EEF-mixed” mention here, I mean later/EEF-admixed Corded Ware and the scenario of Bell Beaker as a northwestern extension of it, rather than both of them having a common origin further east on the steppe and following different trajectories to the west altogether.
Besides natural fermentation there is also simply cooking with it, making thickish soups or stew.
The winner had to be cheese, though, just in terms of transportability, longevity and reduction in lactose content. And the greater satisfaction in having something solid to chew. (Anyone who has had to live on a purely liquid diet for more than a year like I did will know what I’m talking about.)
Jared Diamond tried to make us believe that Nordic people living in Greenland lived on nothing but cheese. (That was before archaeologists had excavated enough to find all of the fish bones.)
IIRC, the oldest known evidence for cheese making in Europe was in Poland 8,000BP.