Famine and disease drove the evolution of lactose tolerance in Europe

Prehistoric peoples in Europe consumed milk thousands of years before humans developed the genetic trait allowing us to digest lactose from milk sugar as adults, according to a new study. The research, published in Naturemapped prehistoric patterns of milk use over the past 9,000 years, providing new insights into milk consumption and the evolution of lactose tolerance.

Until now, it was generally assumed that lactose tolerance arose because it allowed people to consume more milk and dairy products. But this new research, led by scientists from the University of Bristol and University College London (UCL) alongside collaborators from 20 other countries, shows that starvation and exposure to infectious diseases best explain the changes in our ability to consume milk and other unfermented products. dairy products.

While most European adults today can drink milk without discomfort, two-thirds of adults in the world today, and almost all adults 5,000 years ago, may experience problems s they drink too much milk. This is because milk contains lactose, and if we don’t digest this unique sugar, it will travel to our large intestine where it can cause cramps, diarrhea and flatulence; known as lactose intolerance. However, this new research suggests that in the UK today these effects are rare.

Professor George Davey Smith, Director of the MRC’s Integrative Epidemiology Unit at the University of Bristol and co-author of the study, said: “To digest lactose we need to produce the enzyme lactase in our intestine. Almost all babies produce lactase, but for the majority of people around the world, this production declines rapidly between weaning and adolescence. However, a genetic trait called lactase persistence has evolved several times over the past 10,000 years and has spread to various milk-drinking populations in Europe, Central and South Asia, the Middle East and Africa. Today, approximately one-third of adults worldwide are lactase persistent.

By mapping milk use patterns over the past 9,000 years, probing the UK Biobank and combining ancient DNA, radiocarbon and archaeological data using new computer modeling techniques, the team was able to show that the genetic trait of lactase persistence was not common until about 1,000 years ago. BC, almost 4,000 years after its first detection around 4,700-4,600 BC.

“The genetic variant of lactase persistence has been driven to a high frequency by a kind of turbocharged natural selection. The problem is that such strong natural selection is hard to explain,” added Professor Mark Thomas, professor of evolutionary genetics and co-author of the study at University College London.

In order to establish how lactose persistence evolved, Bristol School of Chemistry study leader Professor Richard Evershed assembled an unprecedented database of nearly 7,000 organic animal fat residues from of 13,181 pottery fragments from 554 archaeological sites to find out where and when people were consuming milk. His findings showed that milk was widely used in European prehistory, dating back to the first agriculture nearly 9,000 years ago, but rising and falling in different regions at different times.

To understand how this relates to the evolution of lactase persistence, the UCL team, led by Professor Mark Thomas, built a database on the presence or absence of the genetic variant of lactase persistence using ancient published DNA sequences from over 1,700 prehistoric European and Asian individuals. . They first saw it about 5,000 years ago. 3,000 years ago it was at appreciable frequencies and is very common today. Next, his team developed a novel statistical approach to examine the extent to which changes in milk use over time explain natural selection for lactase persistence. Surprisingly, they found no relationship, although they were able to show that they could detect that relationship if it existed, challenging the long-held view that the use of milk was the cause of the evolution of lactase persistence.

Professor George Davey Smith’s team had probed data from the UK Biobank, comprising genetic and medical data for over 300,000 living individuals, found only minimal differences in milk drinking behavior between genetically persistent and non-persistent in lactase. Critically, the vast majority of people who are genetically non-lactase persistent have not experienced any negative short- or long-term health effects when consuming milk.

Professor Davey Smith added: “Our findings show that the use of milk had been widespread in Europe for at least 9,000 years, and that healthy humans, even those who were not lactase persistent, could to consume milk without getting sick. However, drinking milk in lactase-non-persistent individuals leads to an elevated lactose concentration in the gut, which can aspirate fluid into the colon, and dehydration can result when associated with diarrheal disease.

“If you are healthy and the lactase is not persistent, and you drink a lot of milk, you may feel some discomfort, but you are not going to die of it. However, if you are severely malnourished and have diarrhea, you have life-threatening problems.When their harvests failed, prehistoric people would have been more likely to consume high-lactose unfermented milk – exactly when they shouldn’t.

To test these ideas, Professor Thomas’ team applied indicators of past starvation and exposure to pathogens in their statistical models. Their results clearly supported both explanations – the lactase persistence gene variant was subject to stronger natural selection when there were indications of more starvation and more pathogens.

The authors concluded: “Our study demonstrates how in later prehistory, as populations and settlement sizes increased, human health would have been increasingly affected by poor sanitation and increased diarrheal disease, especially those of animal origin. Under these conditions, milk consumption would have led to increased mortality rates, with individuals lacking lactase persistence being particularly vulnerable. This situation would have been further exacerbated under famine conditions, when disease and malnutrition rates increase. This would lead to individuals who do not carry a variant copy of the lactase persistence gene being more likely to die before or during their childbearing years, increasing the prevalence of lactase persistence in the population.

“It appears that the same factors that influence human mortality today drove the evolution of this amazing gene throughout prehistory.”

The study was funded by the Royal Society, the RCUK – Medical Research Council (MRC) and the Natural Environment Research Council (NERC) and the European Research Council.

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