The human body is home to thousands of genes, each providing instructions for making proteins that perform specific functions. One such gene, the ATP-binding cassette sub-family C member 11 (ABCC11), belongs to a large family of membrane transporter proteins. Its primary role is to move various molecules, including lipophilic anions and steroids, across the cell membranes of specialized tissues. This foundational function in cellular transport underpins the gene’s unexpected influence on several visible human traits.
The Genetic Switch
The dramatic phenotypic differences linked to the ABCC11 gene trace back to a small alteration in its DNA sequence. This change is known as a non-synonymous single nucleotide polymorphism (SNP), identified as rs17822931. At position 538 of the gene, the common allele contains a Guanine (G) nucleotide, while the variant allele features an Adenine (A) nucleotide.
This G-to-A substitution dictates a change in the resulting protein structure. The G allele codes for the amino acid Glycine at position 180 of the ABCC11 protein, while the variant A allele codes for Arginine. This change, designated Gly180Arg, severely compromises the protein’s function.
The variant ABCC11 protein, featuring Arginine, is structurally unstable and cannot undergo N-linked glycosylation. Recognized as misfolded within the endoplasmic reticulum, the cell’s quality control system tags it for destruction. This process leads to a non-functional or severely impaired ABCC11 transporter that is not properly expressed on the cell surface.
Phenotypes of the ABCC11 Gene
The loss-of-function resulting from the A allele directly impacts the apocrine glands, manifesting in two physical characteristics. The most observable effect is the determination of earwax consistency, or cerumen type. The presence of at least one wild-type G allele (genotypes GG or GA) results in the dominant, wet, and sticky earwax phenotype.
Individuals who inherit two copies of the variant A allele (genotype AA) exhibit the recessive, dry, and flaky earwax phenotype. The functional ABCC11 protein actively transports lipid and protein components into the ceruminous gland secretions, contributing to the wet consistency. The absence of this transport activity in AA individuals leads to reduced secretion of these compounds and a drier cerumen.
The second major phenotype linked to the ABCC11 gene is a reduction in axillary body odor. Body odor is caused by skin bacteria breaking down odorless precursor molecules secreted in apocrine sweat, such as sulfur-containing compounds. The functional ABCC11 protein efficiently transports these odor precursors into the apocrine sweat glands. Individuals with the loss-of-function AA genotype do not transport these precursors, meaning the bacteria lack the necessary substrate, leading to a lack of typical musky odor.
Global Distribution of the ABCC11 Allele
The distribution of the ABCC11 alleles across human populations shows a distinct geographical pattern. The variant A allele, which causes the dry earwax and reduced body odor phenotypes, is overwhelmingly prevalent in East Asian populations. In groups such as the Chinese, Koreans, and Japanese, the frequency of the A allele can be as high as 80% to over 95%.
This high frequency creates a clear genetic distinction compared to other global populations. The A allele is nearly absent in African populations, and European populations show a low frequency, with estimates suggesting only about 2% carry this variant. The global pattern shows a distinct north-south and east-west gradient, with the highest concentrations centered in Northeast Asia.
This clustered distribution suggests the A allele likely arose in Northeast Asia and subsequently spread. The gradient indicates that while the ancestral G allele (wet earwax/odor) is dominant worldwide, the variant A allele became fixed at a high frequency in this region. This pattern of geographic clustering indicates a localized selective pressure.
Evolutionary Hypotheses
The prevalence of the loss-of-function ABCC11 A allele in East Asia suggests its spread was driven by a selective advantage. The most discussed explanation is the cold climate adaptation theory. This hypothesis posits that the dry earwax and reduced secretion phenotype conferred a benefit to early human populations migrating into the cold environments of ancient North Asia.
One mechanism relates to apocrine secretions and their role in thermoregulation. The dry earwax phenotype, involving reduced lipid and protein secretion, may have optimized the body’s use of lipids or altered cerumen composition in a frigid climate. Furthermore, the reduction in apocrine sweat and body odor offered an advantage by minimizing evaporative heat loss from the skin surface.
Another angle is that the AA genotype provided protection against certain pathogens or diseases. Regardless of the precise mechanism, the rapid increase in the allele’s frequency points to a strong evolutionary “sweep” that favored the dry earwax, low body odor trait in the ancestors of modern East Asians.