It is, when you think about it, sort of weird that nearly all mammals lose the ability to digest milk early in life. The Class Mammalia is, after all, defined by the gland that produces this life-giving fluid—supplier not only of necessary nutrients but also of water and molecules that protect against continual assaults from invading organisms.
If it strikes me as odd that 5000-plus species are classified on the basis of an anatomical feature that produces a very temporary physiological event, it’s clear the classification makes conceptual sense. Short-lived it may be, but lactation is, admittedly, unique to Mammalia.
And humans are typical mammals. After weaning, most of us no longer produce lactase, known more precisely as lactase-phlorizin hydrolase (LPH), but we’ll sacrifice precision here and stick with lactase. Lactase is the enzyme that snips lactose, the indigestible sugar in milk, into its two component parts, the sugars glucose and galactose. Those two the body can handle easily and use for fuel. Milk sugars are useless to us until they are broken in two.
The gene that codes for lactase, called LCT, becomes mostly nonfunctional after infancy in mammals. As a result, the majority of people don’t drink milk once they are weaned. Many experience painful GI symptoms if they do. Most don’t even consume fermented milk products like yogurt, where microbes have obligingly predigested lactose into its component sugars, and which even the lactose intolerant can often tolerate. Many people avoid cheese too, even though cheese-making discards the whey that contains most of milk’s lactose.
How the mutants prosper
So you might say that, compared to other mammals, the many people who go on pumping out lactase, retaining the ability to consume dairy products in adult life without unpleasant gastric consequences, possess a genetic abnormality. Not that many of us who are abnormal in this way—I’m one of them—are not glad of it. Life would be less pleasurable without latte and ice cream and cheesecake and lasagne and Greek yogurt and a big foamy glass of very cold milk with your cookies.
For the ancestors who passed this genetic abnormality on to some of us, milk may have been a pleasure, but, more important, milk may have been life itself. The adult ability to consume milk—it’s called lactase persistence–is a recent evolutionary development. It arose only in the last few thousand years, a product of natural selection that is believed to have conferred survival advantages on the favored few and so spread rapidly. This speedy spread is strong evidence that lactase persistence provides an impressive selective advantage. You can drink milk safely even if only one of your two lactase genes keeps churning out the enzyme.
There are several roads to lactose tolerance in adulthood. They include a handful of known mutations that coax the lactase gene to keep on working past early childhood. The trait was apparently so useful that when a mutation keeping the gene in operation popped up, it tended to spread quickly. Different mutations that arose in different parts of the world have all led to lactase persistence, making the trait an excellent example of convergent evolution in Homo sap.
Lactase-persistence mutations are not in the lactase gene
This being genetics, there are complications. So here’s the interesting complication about lactase-persistence mutations. They do not occur in LCT, the lactase gene itself. Instead they happen in a gene nearby on chromosome 2 called MCM6. The MCM genes, which are very old, code for mini-chromosome maintenance proteins that are essential for initiating genome replication in eukaryotes. (And eukaryotes, you’ll recall, are organisms with an organized nucleus—which means pretty much anything that isn’t a microbe.)
MCM6 contains regions that can enhance the activity of lactase genes. This makes sense. Lactose intolerance occurs because lactase gene production is slowed and stopped naturally in the Class Mammalia. To keep the lactase gene producing, it is not necessary to change the gene itself. What matters is controlling the switch(es) that slow it down and turn it off. And that’s what the lactase-related MCM6 mutations do: govern how the lactase gene behaves. They keep the switch set at ON.
Lactase persistence is common in Europe and Eurasia and near universal in the British Isles and southern Scandinavia. It is common also in the Arabian Peninsula and fairly common in India, where the cow is sacred. It is rare in East Asia. There are also several isolated pockets of lactose tolerance in Africa, a tale we’ll get to in a moment.
Coevolution of genes and culture
If lactase persistence is one of the best examples of convergent evolution, it is also a superb example of co-evolution of genes and culture. In 2011, an international team of researchers observed, “If the cultural inheritance of an environment-modifying human activity persists for long enough to generate a stable selection pressure, it will be able to co-direct human evolution. There are many examples of this in human evolution but none are so well studied, clear-cut, widespread and well supported as the coevolution of lactase persistence (LP) and dairying.”
Dairying appears to have been the cultural practice that encouraged these terribly useful genetic mutations to spread over much of the world in just a few thousand years. What came first—this is the most prevalent idea—was the herding and domestication of cattle and a few other mammals such as camels and goats. At first this had nothing to do with milk. The animals, goes the theory, were originally domesticated for their labor and their meat.
But when lactase-persistent mutations appeared, the mutants could take advantage of the additional resource offered by milk. They survived better than their normal neighbors, and reproduced more, and the mutations spread because pastoralists move around a lot. Milk, remember, is not just full of nutrients, it is also mostly water. Water is always a valuable resource and often in short supply, especially in dry parts of the world like Africa.
Lactose tolerance in Africa
A paper published just last week demonstrates persuasively the link between lactase persistence in Africa and dairying. It came from the lab of Sarah Tishkoff, University of Pennsylvania authority on African human genetics. It was the largest study ever of lactase persistence in Africa and involved much bigger sample sizes than in the past.
The researchers drew blood and sequenced gene regions suspected of influencing lactase gene expression in 819 Africans from 63 different African populations and also in 154 non-Africans from 9 populations in Europe, the Middle East, and Asia. All hail Alessia Ranciaro, Tishkoff’s postdoc and the paper’s first author, leader of the study, which took her to places where travel and communication are tough. To appreciate the work involved, see Helen Thompson’s article in Smithsonian, which delves into how the researchers did the testing.
The mutation associated with most lactase persistence in Europeans, T-13910, is estimated to have arisen between 5,000-12,300 years ago, about the same time that cattle domestication began in North Africa and the Middle East. Cattle domestication is generally dated at around 10,000 years ago. The researchers found the same variant in pastoralist groups from central and northern Africa, which suggests that those groups mixed with non-Africans at some point.
This may have occurred, the researchers speculate, within historical times, perhaps a result of Roman settlements in North Africa. Razib Khan suggests that T-13910 could have accompanied the Vandals, barbarians from southern Scandinavia and northern Germany, who conquered North Africa in the 5th century AD.
Another mutation, G-13915, common in the Arabian Peninsula, also occurs in northern Kenya and Sudan. It’s an estimated 5,000 years old, which coincides with archaeological evidence for the date of camel domestication. The mutation G-13907 was identified in Ethiopia and northern Sudan and Kenya. That variant may have originated among Ethiopians who then moved to Kenya and Sudan in the last 5,000 years.
The mutation C-14010, found in Tanzania, Kenya, and southern Africa, is thought to have arisen between 3,000-7,000 years ago, at the same time that pastoralists from North Africa migrated to East Africa. The researchers believe C-14010 spread into southern African recently, perhaps in the last 1,000 years.
Some Africans seem to be able to digest lactose for no known genetic reason. That could mean, the researchers say, that other lactase persistence mutations remain to be discovered. Or—an intriguing possibility—perhaps what has adapted to continued lactose is not their genomes, but their microbiomes. The team is now investigating gut microbe populations in Africans.
Tabitha M. Powledge is a long-time science journalist and a contributing columnist for the Genetic Literacy Project. She writes On Science Blogs for the PLOS Blogs Network. New posts on Fridays.
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