Have you ever drunk a big glass of milk or eaten an ice cream cone and then felt sick to your stomach afterwards? If so, you might be one of the estimated 30-50 million Americans who have difficulty digesting milk and other dairy products and are said to be “lactose intolerant” (lactose is the sugar present in dairy products such as milk). Worldwide, the ability to drink milk as an adult is actually a rare one. Babies, of course, need to be able to digest the energy-rich lactose sugar in their mother’s breast milk, but for most people the ability to break down lactose disappears during childhood as expression of the gene that allows digestion of lactose gradually gets turned off. However, the percentage of adults who retain the ability to digest lactose (this ability is referred to as “lactose tolerance”) as adults varies greatly among different populations. Scientists investigating why some populations have higher rates of lactose tolerance have found that this ability is likely to be intricately connected to the agricultural habits of our distant ancestors.

What Does the Lactase Enzyme Do?

To drink milk without feeling sick, humans need to be able to break down, or metabolize, the lactose sugar in milk into smaller components our bodies can use for energy. The enzyme that metabolizes lactose is called lactase and is produced primarily in the lining of the small intestine. The lactase enzyme breaks down the large lactose sugar into smaller sugars that can easily pass through the intestinal wall and enter the bloodstream. When there is insufficient lactase, the lactose sugar doesn’t get broken down and cannot enter the bloodstream, instead lingering in the intestine. There, it provides an abundant food source for intestinal bacteria, which begin to ferment the lactose. As the bacteria consume the lactose sugar, they produce gas, particularly in the colon, leading to the bloating and cramping symptoms lactose intolerant people experience after consuming too much dairy.

The Genetics of Lactase

Lactose tolerance runs in families, providing evidence of a strong genetic component to the trait. Although scientists knew that lactose tolerance must be influenced by genetics, for a long time they didn’t understand the genetic mechanism behind the differences in lactose tolerance among people and populations. They compared the DNA sequence of the gene that encodes the enzyme lactase in lactose tolerant and intolerant populations but were unable to identify any consistent differences between the two groups. In 2002, scientists from Finland examined a broader region of DNA, one that included not only the lactase gene itself, but also the regions flanking the gene (regions next to genes often include important regulatory sequences that determine when genes are turned on and off and the amount of protein that is produced). They identified a change in the DNA just outside the lactase gene that was present in lactose tolerant people and absent in lactose intolerant people. This mutation changes the expression level of the lactase gene: when the mutation is present, a large quantity of the lactase protein is produced; when the mutation is absent, very little lactase is made.

Human Evolution in Action

Now we understand a little bit more about the molecular and genetic reasons why some people are lactose tolerant and others are not, but the question of how and why lactose tolerance evolved in the first place remains. Lactose tolerance is much more common in people of European ancestry (up to 90% of people in northern Europe are lactose tolerant) than in many populations from other parts of the world (in Asian and West African populations, for example, rates of lactose tolerance range from about 1-20%). Scientists theorized that the historical prevalence of dairy farming, especially in northern Europe, might be related to the high rate of lactose tolerance observed there. Before dairy herding began, there was no advantage to being able to consume milk as an adult because no milk was available. But after dairying started, those individuals who could digest lactose into adulthood had a “fitness advantage” over those who couldn’t—lactose tolerance allowed individuals to drink milk from the cattle they were raising in addition to eating their meat. In 2004, one research group provided support for this hypothesis when they determined that the mutation responsible for lactose tolerance in Europe showed what is referred to as a “strong signature of positive selection.” Although this mutation only arose very recently in evolutionary terms, it reached a high population frequency very rapidly, indicating that it was under enormous selective pressure, likely because of the survival advantage that it provided.

Scientists are now trying to figure out more about the historical context in which lactose tolerance evolved. In particular, they would like to know whether lactose tolerance became more common after dairying began or whether populations with a high prevalence of lactose tolerance adopted dairying. A recently published study suggests that in Europe, it is more likely that dairying began first. Scientists analyzed DNA from ancient skeletons of early Neolithic Europeans to test for the presence of the mutation associated with lactose tolerance in Europeans. The absence of the European lactase mutation in the Neolithic DNA led them to conclude that the practice of dairying probably arose first, driving the prevalence of the mutation up with it.

Lactose Tolerance in Africa

Until recently, most of the research studying lactose tolerance had been conducted in European-derived populations. But northern Europeans aren’t the only ones worldwide with a high prevalence of lactose tolerance—certain East African populations (as in Europe, primarily those with a history of dairying) are also highly lactose-tolerant. When scientists looked at DNA samples from East African populations, they observed the European lactase mutation only infrequently. Another research group recently identified three new closely related mutations in East African dairying populations associated with lactose tolerance. Like the European mutation, the East African mutations are located just outside the lactase gene itself and increase expression of the lactase enzyme. The East African mutations also show the same type of strong evidence of positive selection—they arose very recently in evolutionary terms (about 7,000 years ago) and quickly became highly prevalent in the cattle herding populations.

The existence of separate mutations in European and African populations that both confer the ability to digest lactose is a textbook example of “convergent evolution.” These mutations arose independently in different populations, likely in response to the same evolutionary pressure—the survival advantage gained by being able to digest milk from cattle. So, where your ancestors came from and whether they herded cattle is probably connected to whether you can eat ice cream with abandon or whether you have to watch your dairy intake closely.

— Zofia Gajdos, Harvard Medical School

For More Information:

The New York Times’ coverage of this story: “Study Detects Recent Instance of Human Evolution,” Nicholas Wade, New York Times, December 10, 2006 <http://www.nytimes.com/2006/12/10/science/10cnd-evolve.html?ex=1323406800&en=6576a01a1bb4ce31&ei=5090&partner=rssuserland&emc=rss>

For a more detailed explanation of how scientists uncovered the lactase enzyme mutations in African populations (including fascinating descriptions of the challenges associated with doing research in remote areas): “How Africa Learned to Love the Cow,” Erika Check, Nature, 444: 994-996, December 2006.

Primary Literature:

Bersaglieri, T., P.C. Sabeti, N. Patterson, T. Vanderploeg, S.F. Schaffner, J.A. Drake, M. Rhodes, D.E. Reich, J.N. Hirschhorn. 2004. “Genetic Signatures of Strong Recent Positive Selection at the Lactase Gene.” Am. J. Hum. Genet. 74: 1111-1120.

Tishkoff, S.A., F.A. Reed, A. Ranciaro, B.F. Voight, C.C. Babbitt, J.S. Silverman, K. Powell, H.M. Mortensen, J.B. Hirbo, M. Osman, M. Ibrahim, S.A. Omar, G. Lema, T.B. Nyambo, J. Ghori, S. Bumpstead, J.K. Pritchard, G.A. Wray, P. Deloukas. 2007. “Convergent adaptation of human lactase persistence in Africa and Europe.” Nature Genetics, 39: 31-40.