Lactose tolerance evolved a few times independently.

An exciting story has unraveled over the past few years, and a new landmark study caps the effort of dozens of scientists around the world. The problem: why do around half the people in the world have lactose intolerance and what is different about those that can tolerate lactose? While deciphering this question, we now have very strong evidence that humans are still evolving.

Lactose Tolerance and Intolerance

Lactose is the main milk sugar. Young humans are able to digest lactose due to our bodies being able to turn on a gene called lactase, the gene that digests lactose. Sometime between the ages 2-5 years old, most of us turn off the lactase gene, and so we stop being able digesting lactose.

When that happens, the lactose remains in our intestines and is not absorbed. This excess can lead to the lactose intolerance symptoms of bloating and even diarrhea. However, geneticists have noticed that some adult humans are still able to digest lactose... so what gives?

Lactose Intolerance Around the World

Lactose intolerance varies with populations around the world, a strong hint there is a genetic basis for it. According to the UK National Health Service, lactose intolerance frequencies are:

• 95% of Asian people
• 75% of Afro-Caribbean people
• 50% of Mediterranean people
• 10% of northern European people

A more detailed breakdown is provided over at Wikipedia, which correctly states the Swedes (and generally northern Europeans) have low incidence of lactose intolerance.

Controlling the Lactose Gene

So what's the genetic basis of lactose intolerance? The answer came in 2002: Scientists in Finland studied nine extended Finnish families with some members having lactose intolerance and some tolerant. They found two genetic variations (mutations) 100% correlated with tolerance or intolernace. The first one is known as C/T-13910, meaning it is 13910 nucleotides (DNA letters like G, A, C, and T) before the start of the lactase gene. The second is G/A-22018, which is a further 8000 nucleotides upstream. To complicate the matter, C/T-13910 was found in the middle of another gene, known as MCM6.

Fortunately, a follow-up study suggested that it wasn't MCM6 that was responsible for tolerance/intolerance, but that the mutation of C/T-13910 was actually part of the region that switches the lactase gene on and off - i.e., lactose intolerance is simply due to switching off the gene as people grow older. They also found that the second mutation (G/A-22018) was not 100% correlated with tolerance, but may still have a small effect if found.

So that's great news, why are we still studying it?

It Evolved Four Times

Here is the kicker: The new study (published today) has found evidence that there are four different mutations correlated with lactose tolerance around the world. Not only that, these four are completely independent of each other. This is very strong evidence of convergent evolution.

In convergent evolution, different population acquire the same trait independent of each other. What's neat is that, genetically, these acquisitions are different. By studying 470 Tanzanians, Kenyans and Sudanese, the researchers found three new mutations in addition to C/T-13910. They called them G/C-14010, T/G-13915 and C/G-13907. As we saw above, the numbers refer to the distance from the start of the lactase gene, so it's good to see all of them around the same area. This simply means that they are different mutations in different places of the same control region of the lactase gene.

The other neat thing about these four mutations is that they are very recent: within the past 7000 years or so. In evolutionary terms, that's like a minute ago. Interestingly, the populations who have the lactose tolerance mutations are the same populations that historically - in the past 7000 years - started domesticating cattle. What this means is that as people started depending on cow milk as a food, the evolutionary pressure selected for people who could tolerate lactose better. In fact, the selective advantage of having these mutations meant nearly ten times as many offspring as those who didn't have those mutations. This is a very strong advantage which led to the rapid penetration of the mutations into the population.

Lactose Intolerance in Babies

As the story was unraveling, another one was emerging: it turned out that some babies are born with lactose intolerance, a disease called Congenital Lactase Deficiency (CLD). An international collaboration studying CLD found that the lactase gene itself is mutated, that is, the lactase gene is nonfunctional. This is completely different from the more common lactose intolerance that kicks in later in life.

What about the Cows?

It's not just the humans that evolved during domestication: the genes controlling the cow milk were evolving too! Domestication is a well-known evolutionary framework (called artificial selection), and Darwin talked about it extensively in his Origin of Species book. The study on cow milk evolution looked at six cow milk genes and found that they too evolved in a pattern reminiscent of the human populations that domesticated them. This is called coevolution, meaning that two different species evolved in parallel in a related manner.

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