The EDAR gene, or Ectodysplasin A Receptor gene, provides instructions for creating a protein involved in early human development. This gene plays a foundational role in forming various structures that originate from the ectoderm, the outermost layer of cells in a developing embryo. These structures include skin, hair, teeth, and sweat glands, highlighting its broad impact on human physical diversity and evolutionary trajectories.
The Biological Role of the EDAR Gene
The EDAR gene directs the production of a protein known as the ectodysplasin A receptor. This receptor is a central component of the ectodysplasin signaling pathway, active during embryonic development. Within this pathway, the ectodysplasin A receptor interacts with ectodysplasin A1.
This interaction initiates chemical signals inside cells. These signals regulate cell division, growth, and maturation, necessary for ectodermal structure formation. The pathway facilitates communication between the ectoderm and mesoderm, another embryonic cell layer. This signaling is required for the development of hair follicles, sweat glands, and teeth. This pathway’s activation involves recruiting adapter proteins like EDARADD and activating downstream signaling pathways, such as NF-κB and JNK.
Physical Traits Influenced by EDAR
Variations in the EDAR gene are associated with several physical characteristics. One effect is on hair morphology, where EDAR variants contribute to thicker hair shafts. These variants are also linked to straighter hair, a trait observed in East Asian populations.
The EDAR gene also influences dental development, particularly the shape of incisors. A specific variant is linked to “shovel-shaped incisors,” characterized by prominent ridges on the inner surface of the upper front teeth. This feature is prevalent in East Asian and Native American populations, and the variant can also affect tooth size.
Beyond hair and teeth, EDAR impacts glandular structures. It is associated with an increased number of eccrine sweat glands, important for thermoregulation. Research in mice has linked elevated EDAR signaling to enlarged sebaceous and Meibomian glands, and more branched salivary and mammary glands. These influences extend to facial features, including ear morphology and reduced chin protrusion, demonstrating the gene’s widespread developmental role.
The EDARV370A Allele and Human Adaptation
EDARV370A (rs3827760) is a genetic variation within the EDAR gene that has played a notable role in human evolution. Computational analyses suggest this allele originated in central China approximately 30,000 to 35,000 years ago. Ancient DNA evidence indicates it was not universally present in very early East Asian remains, suggesting its rise in frequency occurred after its origin.
This allele exhibits one of the strongest signals of positive selection detected in the human genome. Its frequency increased rapidly in certain populations, beyond what would be expected by genetic drift. Evidence for this strong selection comes from analyses of long-range haplotypes and population differentiation.
The EDARV370A allele is found at high frequencies in East Asian populations, with studies showing frequencies of approximately 87% in Koreans and 78% in Japanese. The allele is also prevalent in Native American populations, suggesting its spread during the peopling of the Americas. In contrast, EDARV370A is virtually absent or at very low frequencies in African and European populations, underscoring the region-specific selective pressures that drove its rise.
Hypotheses for Positive Selection
The prevalence of the EDARV370A allele in East Asian and Native American populations has prompted several hypotheses regarding the selective pressures that favored its spread. One theory centers on climate adaptation, concerning sweat glands. This hypothesis suggests that an increased number of eccrine sweat glands, associated with EDARV370A, offered a survival advantage in hot and humid climates due to enhanced thermoregulation.
Another climate-related hypothesis proposes adaptation to cold and dry environments. This theory posits that the allele’s influence on enlarged sebaceous glands, which produce skin-lubricating sebum, could have provided a protective barrier against desiccation and heat loss from exposed skin and hair. This effect, combined with thicker hair, might have offered an advantage in environments like Beringia during the Last Glacial Maximum.
A third hypothesis focuses on nutrient processing, related to vitamin D and breast milk. This theory suggests that increased mammary gland ductal branching associated with EDARV370A could have amplified the transfer of nutrients, including vitamin D, from mother to infant. This might have provided an advantage in high-latitude environments where low UV radiation limited vitamin D synthesis, making efficient nutrient transfer through breast milk beneficial for infant health.
Connection to Ectodermal Dysplasia
While variations in the EDAR gene are associated with normal human traits, severe mutations can lead to developmental disorders. Hypohidrotic Ectodermal Dysplasia (HED) is the most common form of ectodermal dysplasia, characterized by abnormal development of ectoderm-derived structures. Mutations in the EDAR gene account for approximately 10% of HED cases.
When EDAR gene mutations cause the ectodysplasin A receptor to be non-functional or have reduced activity, the signaling pathway for ectodermal development is impaired. Individuals with HED often experience sparse hair (hypotrichosis) and can have absent or malformed teeth (hypodontia or oligodontia). A hallmark symptom of HED is hypohidrosis (reduced sweating) or anhidrosis (complete inability to sweat), directly contrasting with the increased sweat gland density associated with the EDARV370A allele.