Traditionally, being able to digest lactose simply offered people nutritional benefits, and so over the course of history, the ability to digest it spread to certain populations. However, according to one study, two other selection factors probably played the decisive role in the spread: disease and famine. Lactose-intolerant people who consumed milk were more affected by these stresses and were more likely to die than people with inherited lactose intolerance, the researchers explain.
Most of us are adapted to drinking milk: the majority of adult Europeans can digest the popular food without any problems because they produce the enzyme lactase in their intestines, which can break down lactose. This ability is based on what is known as lactase persistence – a genetic trait that means that enzyme production is maintained well into infancy. However, this is not the case for most people worldwide: Two-thirds of adults cannot digest lactose and this is how it ends up in their large intestine. In larger quantities, this can then lead to symptoms of lactose intolerance: flatulence, diarrhea and cramps can occur.
Until now, it was thought that lactose tolerance arose because it allowed people to consume more milk and dairy products. This is because the genetic trait for lactase persistence has evolved multiple times over the past 10,000 years and has spread to diverse milk-drinking populations in Europe, central and southern Asia, the Middle East and Africa. However, the speed at which the predisposition spreads seems very high: “The genetic variant of lactase persistence was apparently brought to a high frequency by a kind of turbocharged natural selection. Such strong natural selection is difficult to explain,” says senior author Mark Thomas from University College London. That is why he and his colleagues have devoted themselves to the question of how the strong spread could have come about. “To do this, we first had to clarify where and when people consumed milk,” says lead author Richard Evershed from the University of Bristol.
On the trail of milk consumption and lactose tolerance
As a basis for their study, the scientists first developed a database with almost 7000 organic residues from archaeological ceramic vessels. It reflects that in European prehistory, milk was used extensively from the beginning of agriculture almost 9000 years ago. The researchers then linked this information on prehistoric milk use with their study results on the evolution of lactase persistence. These were based on data from studies of ancient DNA sequences derived from more than 1700 prehistoric individuals. According to this, the predisposition to lactase persistence first appeared about 5000 years ago. 3000 years ago it was already present in a significant frequency, and today it is very common, especially in northern Europe, according to the evaluations.
The researchers then applied a statistical technique to examine the extent to which changes in milk consumption over time explain natural selection for lactase persistence. In concrete terms, this means that the advantage of the predisposition had to be so great that carriers had significantly more offspring than people who were not lactose-tolerant. However, as the researchers report, the rapid spread of the genetic anomaly cannot be explained on the basis of a nutritional advantage or by symptoms. This came from a study of data from the UK Biobank, which includes genetic and medical information from more than 300,000 living individuals. Accordingly, there are only minimal differences in milk drinking behavior between genetically lactase-persistent and non-persistent individuals. Crucially, the vast majority of people who do not genetically exhibit lactase persistence experience no long-term adverse health effects from dairy consumption. These results challenged the long-held view that milk consumption was fundamental to the development of lactase persistence.
Advantage in sickness and hunger
But then what drove this “turbocharged natural selection”? According to the researchers, cofactors appear to have played the crucial role: “In short, milk consumption was widespread in Europe for at least 9000 years and healthy people, even those who did not have lactase persistence, could easily consume milk without getting sick. However, in individuals who do not have lactase persistence, milk consumption leads to high concentrations of lactose in the gut, which can draw fluid into the large intestine, which, combined with diarrhea, can lead to dehydration,” says co-author Davey Smith of the University of Bristol. “I hypothesized that this process could result in high mortality as the infectious disease burden increases, as population sizes and densities increase to levels where some infectious agents can continuously circulate within them.”
Thomas also highlights the possible role of prehistoric famine: “If you’re healthy but not lactase-persistent and you drink a lot of milk, you can get cramps, maybe diarrhea and gas. It’s not pleasant, but it’s not deadly either. However, if you are severely malnourished and have diarrhea, then you have life-threatening problems. And maybe that’s the accelerated natural selection we’re looking for. When their crops failed, prehistoric humans were more likely to consume unfermented milk that was high in lactose—precisely when they shouldn’t.”
To support these explanations, the researchers integrated evidence of past famines and pathogen burdens into their statistical methods. “The results clearly supported both explanations – the lactase persistence gene variant was subject to more natural selection when there were signs of greater famine and more pathogens,” says co-author Yoan Diekmann from Johannes Gutenberg University Mainz.
The team concludes: In the context of starvation and the spread of diarrheal diseases, consumption of milk has likely led to an increase in mortality, with people without lactase persistence being particularly at risk. They were more likely to die before or during their reproductive years, significantly increasing the proportion of people with lactase persistence in the population.
Source: Johannes Gutenberg University Mainz Original publication: Nature, doi: 10.1038/s41586-022-05010-7