Mother’s milk holds the key to unlocking an evolutionary mystery from the last ice age

As biologists explore the variation across the genomes of living people, they’ve found evidence of evolution at work. Particular variants of genes increase or decrease in populations through time. Sometimes this happens by chance. Other times these changes in frequency result from the gene’s helping or hindering individuals’ survival, a phenomenon known as selection. If a gene conferred a survival advantage, people with the mutation would have more offspring and the mutation would become more common in subsequent generations.

Most of those past episodes of selection make sense, as they worked on genes involved with things like resisting disease, blood oxygen levels at high altitudes, and having paler skin at northern latitudes.

However, researchers have also identified an episode of strong selection that doesn’t have such an obvious logic. It’s a mutation on a gene involved with the development of a suite of traits that don’t seem very similar at first glance: hair, teeth, sweat glands and breasts. This one was a mystery — what could have been the adaptive value of this mutation that led to it being common in northeastern Asia but nowhere else?

My research usually focuses on teeth, specifically genetic influences on their development. I came to this particular evolution puzzle when my colleagues and I gathered in Boston at the AAAS meeting last year to discuss the latest evidence of how people first migrated into the Western Hemisphere. We put together the clues about this episode of selection on human genetic variation – and found an example of adaptation to life at high latitude during the last ice age.

Natural selection … of what?

We were trying to understand selection for a mutation in the gene called EDAR – it encodes the ectodysplasin A receptor that plays a role in how tightly cells adhere to each other during the development of hair, teeth, sweat glands and breasts. All of these anatomical structures form via a very similar developmental process that happens while you’re still in your mother’s womb. Slight changes to the developmental mechanism results in the final differences between hair and teeth and sweat and mammary glands. But there is a fundamental similarity that, among other things, includes the activity of EDAR.

This shared development is especially obvious when things go wrong. For example, 1 in 10,000 newborns have a disorder called ectodermal dysplasia, which causes disruption to the development of their hair, teeth, skin, sweat glands and breasts.

The V370A mutation that we focused on, the one that experienced strong selection, doesn’t disrupt development of these structures; rather, it augments them. People with V370A have thicker and straighter hair shafts, and their incisors have extra buttressing on the tongue side – a feature biologists call “shoveling.”

Human upper incisors with significant ‘shoveling’ on the tongue side. Christy G. Turner, II, courtesy G. Richard Scott, CC BY-ND
So why did this mutation provide such an advantage to people who carried it? Mice that have been experimentally induced to have the V370A mutation have thicker fur shafts and increased density of sweat glands. A previous study of modern human genomic variation interpreted the selection to have occurred in northern China during the last ice age and focused on the sweat glands. The researchers suggested that the selection was for improved sweating that could help with regulating body temperature. But to my colleagues and me, that just didn’t feel like a convincing adaptive scenario given that this took place during the (cold) ice age.

Instead of the sweat glands, our attention was drawn to another trait. Mice with the V370A mutation also have an increase in the branching of their mammary ducts – the tiny tubes that intertwine with breast tissue and extract nutrients to make milk. Maybe it was this change in the breast tissue that was so valuable to people with this mutation?

Christy G. Turner II, shown working in 1975, and his students assessed variation in incisor shoveling in over 30,000 people around the world. The current study relied on a subset of these data collected by co-author G. Richard Scott. G. Richard Scott and Joshua P. Carlson, CC BY-ND
Rather than trying to sample DNA from thousands of ancient people’s remains to see if they carried the mutation, we took advantage of the effect V370A has on human incisors. Relying on data collected over many years by my colleague G. Richard Scott from the University of Nevada, Reno, our group looked at the dental variation of over 5,000 skeletons from archaeological sites in Europe, Asia and the Americas to get a sense of how this mutation varied through time.

We found that all of the indigenous people living in the Western Hemisphere prior to European colonization had shovel-shaped incisors, which means they all likely had the V370A mutation. In contrast, only about 40 percent of the people in Asia had shovel-shaped incisors, and essentially no one in Europe did.