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But why is the lactase persistent allele not in HWE?

Dairying, diseases and the evolution of lactase persistence in Europe:

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation—proxies for these drivers—provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

Two issues

1) Doesn’t seem to explain why LP started becoming common in Britain before the continent

2) Why are the alleles not in HWE? There’s not really any assortative mating.

13 thoughts on “But why is the lactase persistent allele not in HWE?

  1. Comment on 1) is that although agree with this, they might have been common in Northern France before Britain or at the same time; we only really have the data on Central Europe that is detailed enough to compare yet?

    On why selection happened in some regions earlier, my suggestion in the open thread was varying selection of cultural commitment to keeping milk animals around as a subsistence strategy during famines/crises.

  2. The alleles of rs4988235 are not in HWE due to the population structure (geographical / ethnic) which is totally expected given how much the allele frequencies differ within Europe. Even between Britain and Ireland, the AFs differ by 10%! And of course within-country HWE deviations are relatively modest. They get huge p-values solely because of the large dataset sizes. Like in Britain, we’re talking about 3 thousand extra homozygous common allele carriers – but it’s a meager 1.7% excess.

    I absolutely agree that the significantly earlier onset of lactase persistence in the British Isles contradicts the authors’ theories (besides, it’s probably too hard to measure the social upheavals of the deep past in a quantitative way, and therefore I find it hard to give credence to their Fig. 6).

    My own pet theory links unfermented milk consumption with the availability of winter feed for the cows. People forget that in the first millennia of milk consumption, milk wasn’t a year-round product yet. Cattle was kept through the winters on near-starvation rations, and the cows hardly have any milk. In those conditions, a hypothetical milk drinker would have lost lactose tolerance after a winter or two. Therefore, consumption of unprocessed milk (perhaps except by the smallest children) couldn’t have become a cultural norm yet. In most of North-Central Europe, year-round availability of milk didn’t happen before the transition from composite wood-flint scythes to metal scythes (in Iron age) made hay abundant. But in coastal climates of the British Isles, winter grazing may have been more abundant, and year-round availability of milk could have made microbiome-driven adult lactose tolerance possible. What’s biologically possible and beneficial, eventually becomes a cultural norm. And once unfermented milk drinking becomes a cultural norm, selection for the LCT persistence begins…

  3. I may not be the only reader reviewing the acronyms for groups like “Western Hunter-Gatherers” and “Ancient North Eurasians”… Recalling Genetics 101, HWE = Hardy-Weinberg Equilibrium.

  4. To add to the winter-feed issue and the seasonality of milk supply, one also needs to remember that even when feed is abundant, the final two months of cow pregnancy are an obligatory “dry period” when milking must stop because a cow can’t sustain producing nutrients both for the fetus and for milk. Any less feed makes dry periods longer. On a traditional cattle farm, calving would be times, approximately, to just before or early in the best grazing season (calves start grazing 1.5-2 months after birth). This window is rather wide in countries like Ireland, where today’s recommended cattle grazing period is 8 months a year, but it narrows in North-Central Europe, down to 5 months in Sweden. A relatively narrow window of desired calving, coupled with longer dry pre-calving periods, would have meant that all cows in a herd must have been dry at the same time.

  5. Scratching my head here. Raw milk turns in 24 -48 hours without refrigeration. It becomes clabber which is still quite consumable. Yogurt, kefir, and other fermented mil products have a “shelf life” of many days even without refrigeration. Fermenting milk has been a known technology for thousands of years in many, widely divergent cultures. In all the fermented milk products, including clabber, it is the lactose that is fermented. The bacteria strains differ. They are all very low in lactose or without it all together. I see how lactase persistence is more advantageous if a population is drinking raw _fresh_ milk. But how common was that?

  6. I guess I do wonder that about this paper; lots of evidence of dairy fats, but is this actually evidence of raw milk drinking? I’ve come up with a hypothesis that, accepts as an axiom that “yes, it is”, but if other people think that its not the case (despite this being presumably slightly less parsimonious without specific evidence for secondary processing?) then does that paper refute it? If that’s not the case, then is a explanation where only some cultures who drank milk did so in conditions of famine, pushing for LP, necessary?

  7. 6 months to 5 years old. That should be the focus of any LP study.

    It’s the time when raw milk is fed to children since the time of the European LBK Neolithic. There are many examples of these specialized ceramic vessels and cow horns for feeding babies and toddlers and the time in which selective pressure is most active.

    Importantly, children develop intolerance at different times based on their race. For many non-LP caucasians, perhaps as late as 5 years. That’s a very long time and affords women to supplement a childs diet with something simple without having to rot adult teeth. It allowed women to space children closer together and ween earlier.

    Some 40 year old guy drinking fermented milk in Shalababastan just doesn’t seem an area to focus on selective pressure. Sorry, but just another paper for the LP paper bonfire.

  8. Dairying was probably worthwhile even without lactose tolerance. Yogurt and buttermilk may be consumable, but butter and cheese are probably the real motivation.

    Butter requires very little technology to produce and is an excellent source of fat. North European people could not grow olives. Oil seeds that grow in that area (rape, mustard) can be toxic and are not easy to extract oil from.

    And cheese, particularly hard cheeses, is very nutritious and can be stored for long periods of time.

  9. @Walter Sobchak, the genetically lactose-intolerant peoples from the Eastern Steppes use two ancient, alternative technologies which parallel the European traditions of butter and hard cheese.
    Kaymak (butter-like super-rich cream product) is, according to the Kyrgyz legends, the earliest dairy product the ancient peoples started to use.
    And qurut (dried fermented-milk or whey balls) is the Steppe’s answer to the problem of long-term storage of dairy products.

  10. “Some 40 year old guy drinking fermented milk in Shalababastan just doesn’t seem an area to focus on selective pressure.”

    The place where there might be strong selective pressure is on mothers, especially pregnant and nursing mothers. There is modern evidence that maternal Vitamin D deficiency impacts fertility, miscarriage and still birth rates, and infant mortality

  11. ohwilleke, I wonder if it’s possible to get an estimate of vitamin D levels from ancient bones. At least bone density should be possible. Could LA persistence follow a change in culture-women required to wear head-to-toe clothing for example?

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