Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk - PubMed (original) (raw)

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

Leslea J Hlusko et al. Proc Natl Acad Sci U S A. 2018.

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.

Keywords: Beringia; UV radiation; adaptation; dental anthropology; mammary epithelium.

Copyright © 2018 the Author(s). Published by PNAS.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Fig. 1.

Geography of Beringia and levels of UV radiation. (A) Map of Beringia today. Cross-hatching indicates the region in which levels of UVMED (defined as the amount of UV radiation that will produce minimal erythema) that reach the Earth’s surface are too low to promote cutaneous synthesis of vitamin D in humans on a year-by-year basis, requiring dietary supplementation (modified from ref. ; projected to show an equal distance map of Beringia). The black and white region marks the Arctic Circle, for which there are no Total Ozone Mapping Satellite Data version 7. Other data show that this region has even less UV-B exposure, as would be expected from the increased latitude. The areas below the Arctic Circle in white and light blue are shallow seas as discerned from modern bathymetry using Etopo2 data, indicating land that would have been exposed during the LGM. (B) Map of Beringia during the LGM showing the exposure of land at 117 m below current sea level and the reconstructed terrestrial environments. The shrub tundra is the only area biologically productive enough to support a human population of the size estimated by molecular data. This population was genetically isolated for ∼2,500–9,000 y during the LGM because of the ice to the east and extensive mesic tundra to the west.

Fig. 2.

Fig. 2.

Overview of breast anatomy, development, milk production, and histology. (A) Genetic influences on milk production summarized from the main text. The rodent, human, and cow figures indicate the systems from which the results are known. (B) Three stages of mammary development alongside the genetic mutations known to increase ductal branching. Hormones induce the pubertal and gestation/lactation stages (denoted in pink). In vitamin D-deficient adipose tissue, ductal branching increases during these two stages of development. The embryonic stage (in green) is not hormonally induced; branching density is influenced by the ectodysplasin pathway (108) and, specifically, increased by EDAR V370A. (C) Cross-section of a ductal lumen showing the bilayer of luminal and myoepithelial cells. (D) Schematic of a desmosome, one of the main adhesive structures between mammary luminal cells. The orange lines represent desmosomal cadherins in the extracellular space. The gray lines in the purple area represent the intracellular filaments. (E) Close-up view of the desmocolin proteins that comprise the desmo-adhesome. An increase in the activity of the ectodyplasin pathway alters the relative proportions of Dsc2 and Dsc3, leading to a reduction in the adhesive strength.

Fig. 3.

Fig. 3.

Relationship between EDAR V370A and degree of incisor shoveling. (A) Current world-wide allele frequencies of EDAR V370A (in yellow) and other EDAR haplotypes (in blue) (data from ref. 29). Because these data are from living people, the Native American data include significant admixture from European colonization, a population with essentially no occurrence of EDAR V370A. These modern data likely vastly underrepresent the occurrence of EDAR V370A among indigenous people before European contact. Current Asian allele frequencies may be higher than pre-LGM frequencies due to back-migration from the Beringian population after the end of the LGM, a migration supported by linguistic data (46). (B) Histogram showing EDAR V370A genotype and degree of incisor shoveling, demonstrating the imperfect but strongly additive nature of _EDAR V370A_’s influence on incisor shoveling (adapted from ref. 43). (C) Frequencies of incisor shoveling scores observed in archaeological populations from Africa, Europe, South Asia, East Asia, North America, and South America (

Table S1

). Purple and blue represent a lack of incisor shoveling, and as such, an individual who is _EDAR V370A_−/−. Note the lack of shoveling scores of 0 and 1, and very low occurrence of 2, in the indigenous people of the Western Hemisphere, indicating a very high frequency of EDAR V370A before European contact.

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