Flatulence has been immortalized in this children’s song: “Beans, beans, the musical fruit / The more you eat, the more you toot.” The same can be said of milk for those of us with lactose intolerance.
Being unable to digest milk sugar as an adult is not absurd. After all, why would we need to keep on consuming a liquid typically produced to feed infants? What is actually strange at first glance is that many human populations developed a way to keep properly digesting lactose past infancy. This ability was long thought to have evolved at the same time as our ancestors began to domesticate cattle and drink their milk, but a recent look at the evidence paints a very different picture.
You may have heard that the difference between people who can digest lactose and those who can’t boils down to a mutation in a gene, but it’s a tad more interesting than that.
Lactose is a type of sugar called a disaccharide, meaning it consists of two simple sugars essentially holding hands. If that hand holding is not taken care of inside our small intestine, the lactose ends up in our colon where two things happen. The presence of lactose draws water out and into the colon, resulting in diarrhea; and bacteria that live in the colon feast on this lactose and release gases like CO2 and hydrogen, which are felt as bloating and expelled as flatulence.
Thankfully, the human body produces a set of molecular scissors that can break this hand holding, preventing this cascade of undesirable events. These scissors are an enzyme called lactase and it is anchored to the cells of our small intestine. Lactase cuts lactose into its two smaller sugars, glucose and galactose, which are then absorbed into the blood.
The fact that some people continue to produce lactase after having been weaned off their mother’s milk is called lactase persistence, and studies eventually confirmed that lactase persistence is inherited.
It wasn’t until the early days of the 21st century, however, that scientists figured out where in the genome this benefit was found. Given that lactase is an enzyme and that enzymes are proteins, lactase is encoded by a gene. But that miraculous little genetic variation that allows certain people to keep drinking milk into adulthood without worry is not in the lactase gene itself.
It is found, as the geneticists call it, “upstream.”
DNA is a sequence of bases we refer to as letters (A, T, C, and G), and 14,000 letters before the beginning of the lactase gene lies a particular stretch that helps regulate when the lactase gene is turned on and produces lactase proteins. This is normal. Genes are not always turned on, just like your favourite brownie recipe is not being used to make delicious brownies 24/7 in your kitchen. That recipe spends most of its time waiting for you to feel a craving. It stands by before being activated. Genes are the same: their expression is tightly regulated.
Upstream of the lactase gene, Finnish researchers found in 2002 a one-letter change in that regulatory region that allowed people to continue producing lactase. How? The new letter creates a landing pad for an important protein that turns the lactase gene on. In effect, it’s a cheat. The body naturally ratchets down the production of lactase as we age by using one pathway, but this one-letter change creates a secret bypass that allows lactase production to persist. It is as if you let go of the gas pedal in your car, but your friend in the back seat activates a hidden rocket booster, so your car keeps on moving forward instead of slowing to a stop.
This one-letter change is not the only way to achieve lactase persistence. Scientists subsequently found a handful of one-letter changes in the regulatory region upstream of the lactase gene. This is an example of convergent evolution. These variants independently and randomly arose in different human populations, and they fulfilled the same role: allowing people to continue digesting milk products well past weaning.
About one in three people worldwide have lactase persistence now, but this advantage is not evenly distributed. It is much more common in people of northern European descent, for example, than in those of East Asian heritage.
Scientists are trained to hypothesize and to then test their hypothesis, and in the case of lactase persistence, one of the leading hypotheses was that this persistence probably evolved in tandem with our domestication of milk-producing animals, which started to happen about 9,000 years ago.
But there were a number of details that didn’t quite add up, and a large study that was just published provides strong evidence that this hypothesis has been milked dry.
Animal milk consumption predates our ability to digest it
The idea of humans consuming the milk of their domesticated cattle and simultaneously evolving lactase persistence—which would have given people with that mutation an advantage over others, by allowing symptom-free consumption of a highly nutritious food source—is appealing.
But why is it that some milk-drinking, cattle-raising cultures, like traditional Mongol and Kazakh herders, rarely have lactase persistence? We may wonder if the milk from the animals they herd has low amounts of lactose, but that is not the case: the mares whose milk they consume is rich in lactose, with amounts similar to that of human breast milk.
Conversely, why is it that the Hadza and Yaaku hunter-gatherers of East Africa, for example, often continue producing lactase into adulthood despite the fact that they rarely drink milk? And why is it that DNA evidence shows that lactase persistence was uncommon in Europe before the Middle Ages?
A team of researchers recently tackled the problem in a big way and published their findings in the journal Nature. Figuratively speaking, they travelled through time to figure out what had happened.
Milk leaves fat residues on the pottery that contains it, and these milk fats can be detected and distinguished from the kind of animal fat that is present in their meat by looking at the length of the fat molecule and the type of carbon atom it contains. The researchers scoured the literature for every study that reported these findings from archaeological digs, and they concluded that the use of milk was quite common all over Europe throughout its prehistory, well before Europeans were able to digest lactose after infancy, which started to become widespread 3,000 years ago.
If this milk that was widely consumed was not digested properly, why did our ancestors stick with it? Why did they not rapidly move to process most or all of their animal milk into derivatives like cheese, which contains much less lactose, for ease of digestion?
The answer seems to lie with us, modern humans. The researchers also questioned the UK Biobank, a massive repository that includes information and DNA on about half a million people. In a subset of that biobank, namely unrelated people of white British ancestry, it turns out that 92% of those who cannot digest lactose still use fresh cow’s milk, and only 2.5% of these milk consumers adhere to a lactose-free diet.
It may be that these lactase-deficient adults do what I do and resort to lactase supplements. Indeed, I am often flummoxed when I hear people who can’t digest lactose complain that they must simply put up with the pain. The enzyme they are lacking—the enzyme I myself am lacking!—can be purchased over-the-counter in most pharmacies. When taken with a meal, the lactase enzyme in the tablet simply slices and dices the milk sugar, thus saving us from gastrointestinal distress.
But as the researchers point out, lactase supplements have only been available fairly recently, and the UK Biobank started recruiting its participants in 2006, so they don’t believe that is what is happening. It seems that for most people who can’t digest lactose, the symptoms are mild enough that they put up with them, and that may be exactly what their ancestors did.
So how did lactase persistence spread throughout these populations that had already been consuming dairy for thousands of years, then? There must have been some reason why lactase persistence made people more fit to reproduce. Especially since, when looking at the modern humans of the UK Biobank, the researchers were unable to find a direct advantage lactase persistence had on mortality, body mass index, or fertility.
The scientists here propose two hypotheses, and it may be that both are true.
Consuming a bit of dairy as part of a diverse diet and experiencing the occasional diarrhea is an inconvenience, but in a famine, this diarrhea can become fatal, either because you are extremely malnourished or because all you have left to consume is milk. Thus, when food became scarce, people who could properly digest dairy had a survival advantage.
But even outside of these food crises, a second hypothesis is that, over time, people started to live in dense areas with a lot of farm animals. Some of these animals carried diseases that could be transmitted to humans. Many of these diseases would have been survivable, but if you were already dealing with gut issues and diarrhea due to your lactose intolerance, these diseases might have tipped you over the edge and killed you off before you had a chance to reproduce.
We are much luckier than our ancestors when it comes to dairy consumption. Many of us have inherited from our parents this amazing, one-letter genetic change that keeps our lactase gene on. Those of us without that good fortune can instead turn to cow’s milk that has been pre-digested with lactase, so-called lactose-free dairy milk, or to vegan alternatives, like soy milk, almond milk, oat milk, and rice milk. Even processed dairy products, like ice cream, yogurt and cheese, are now available in lactose-free and vegan versions. We can also pop a lactase supplement before drinking that tall glass of milk.
Or we can do what our ancestors did for thousands of generations before the advent of that one-letter genetic trick: enjoy milk and put up with the inconvenience.
- Lactose is a sugar found in milk that, if not broken down by the lactase enzyme, can cause bloating, flatulence, and diarrhea
- One in three people worldwide continues to produce lactase after infancy, a trait that is caused by a one-letter change in the stretch of DNA that controls the expression of the lactase gene
- Evidence from archaeological digs and a modern DNA and information repository shows that humans consumed dairy for thousands of years before developing the ability to digest it properly after infancy