Vitamin D Strikes Again To Explain EDAR

Two of the biggest known evolutionary adaptations found in modern humans (as measured by inferred selection on a derived trait from basal Africans) are lactase persistence (found in Northern Europeans and arising around 5000 years ago in Europe) and EDAR (found in all pre-Columbian Native Americans, about 40% of Asians, and almost no Europeans, with an inferred place of origin possibly near Northern China and probably during the last Ice Age about 20,000 years ago, which reached fixation in Beringia).

One leading hypothesis regarding lactase persistence which allows adults to drink cows milk, is that it addressed Vitamin D deficiencies, especially in pregnant and nursing mothers, thereby greatly reducing infant morality. Vitamin D is useful for many purposes, but one of those is as an immune system enhancer.

A similar hypothesis may explain the EDAR mutation in Asians and New World populations according to new research, in what amounts to two different paths of convergent evolution that accomplished similar adaptive results.

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.”

. . . 

It’s not easy to live that far north. Sure, it’s cold. But more importantly, at high latitudes, the sun is lower in the sky so sunlight must travel through more atmosphere to reach Earth’s surface. This journey through the atmosphere mostly filters out the Sun’s ultraviolet radiation. Most life forms need sun exposure to be healthy, in large part because UV exposure induces the body to make vitamin D. 

Lighter skin tones let in more UV and have been selected for multiple times in human history. But once you get to the Arctic, skin depigmentation alone won’t suffice. In order to live with so little UV, people have culturally innovated, eating diets rich in vitamin D, such as oily fish. But nursing infants don’t eat these foods. Babies get their nutrients through their mother’s milk. 

This is where our EDAR gene comes back into the picture. The V370A mutation in mice increases the branching density of the mammary ducts, and very likely does the same exact thing in human breasts. Scientists know that vitamin D deficient conditions induce more ductal branching during the breast development that happens with pregnancy. All of the evidence suggests that the increased ductal branching associated with V370A helped transfer nutrients from mother to infant through breast milk in a population that was extremely vitamin D deficient. 

So the selection wasn’t for thicker hair or shovel-shaped incisors – instead, it was much more likely to have been on mammary ducts. The thicker hair and tooth variation just went along for the ride because they are created by the same basic developmental pathway. Selection on genetic variation in EDAR is probably related to health consequences for nursing infants rather than its effects on hair, teeth or sweat glands.

The process by which the researchers came to this conclusion involved a mix of methodologies and really deserves a read of the whole piece that is linked.

EDAR is also notable from a cultural perspective because the phenotypic traits that it codes for are among the suite of traits frequently used by lay people with limited information as litmus tests for "Asian" descendent and a stereotypical "Asian" appearance. There was a previous post at this blog about EDAR in 2013.

The source paper is:

Significance  

The frequency of the human-specific EDAR V370A isoform is highly elevated in North and East Asian populations. The gene is known to have several pleiotropic effects, among which are sweat gland density and ductal branching in the mammary gland. The former has led some geneticists to argue that the near-fixation of this allele was caused by selection for modulation of thermoregulatory sweating. We provide an alternative hypothesis, that selection instead acted on the allele’s effect of increasing ductal branching in the mammary gland, thereby amplifying the transfer of critical nutrients to infants via mother’s milk. This is likely to have occurred during the Last Glacial Maximum when a human population was genetically isolated in the high-latitude environment of the Beringia.  

Abstract

Because of the ubiquitous adaptability of our material culture, some human populations have occupied extreme environments that intensified selection on existing genomic variation. By 32,000 years ago, people were living in Arctic Beringia, and during the Last Glacial Maximum (LGM; 28,000–18,000 y ago), they likely persisted in the Beringian refugium. Such high latitudes provide only very low levels of UV radiation, and can thereby lead to dangerously low levels of biosynthesized vitamin D. The physiological effects of vitamin D deficiency range from reduced dietary absorption of calcium to a compromised immune system and modified adipose tissue function. The ectodysplasin A receptor (EDAR) gene has a range of pleiotropic effects, including sweat gland density, incisor shoveling, and mammary gland ductal branching. The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers’ milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids. 

Leslea J. Hlusko, et al, "Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk." 115(19) PNAS E4426-E4432 (May 8, 2018; published ahead of print April 23, 2018) https://doi.org/10.1073/pnas.1711788115

Hat tip to DDeden for calling attention to this important article which I did not catch when it came out.