ABCC11

Function

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, an SNP in this gene is responsible for determination of human earwax type and presence of underarm odour. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.

Molecular genetics

The ABCC11 gene is present in the human genome as two alleles, differing in one nucleotide also known as a single nucleotide polymorphism (SNP). A SNP in the ABCC11 gene on chromosome 16 at base position 538 of either a guanine or adenine controls for multiple distinct phenotypes. These respectively code for glycine and arginine in the gene's protein product. Dominant inheritance of the GG or GA genotype is observed while the AA genotype is recessive. The phenotypes expressed by the genotypes include cerumen type (wet or dry ear wax), osmidrosis (odor associated with sweat caused by excessive apocrine secretion), and breast cancer risk, although there is ongoing debate on whether if there is a real correlation of the wet ear wax phenotype to breast cancer susceptibility. The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele. Note this phenotype requires only the presence of one guanine. The homozygous recessive AA genotype produces the dry ear wax phenotype (dry and flaky) and mildly odored sweat.

The alleles containing a guanine produce a protein that is glycosylated but alleles containing an adenine are not glycosylated. The resulting protein is only partially degraded by proteasomes. This effect is localized to ceruminous gland membranes. Because the adenine containing allele protein product is only partially degraded, the remaining functional protein is located on the cell surface membrane which ABCC11 gene's role in sweat odor is likely in part due to the quantitative dosage of ABCC11 protein.

From an evolutionary perspective, the implications of cerumen type on fitness are unknown although odorless sweat in ancient Northern Eurasian populations have been postulated to have an adaptive advantage for cold weather. In some nonhuman mammals, mating signals via release of an odor enhanced by increased apocrine secretion may be a factor in sexual selection.

Physical human traits that are controlled by a single gene are uncommon. Most human characteristics are controlled by multiple genes (polygenes) although ABCC11 is a peculiar example of a gene with unambiguous phenotypes that is controlled by a SNP. Additionally, it is considered a pleiotropic gene.

Demographics

The history of the migration of humans can be traced back using the ABCC11 gene alleles. The variation between ear wax and body odor in ethnicities around the world are specifically due to the ABCC11 gene alleles. It is hypothesized that 40,000 years ago, an ancient northern Mongoloid tribe evolved the dry ear wax phenotype that followed a spread of the dry ear wax allele to other regions of Asia via migration of the ancient tribe. The gene spread as a result of it being a beneficial adaption or through an evolutionary neutral mutation mechanism that went through genetic drift events.

The frequency of alleles for dry ear wax and odorless sweat is most concentrated in Northeast Asia, most notably China, Korea, Mongolia, and mainland Japan. Conversely the frequency of the allele for wet ear wax and odored sweat are highest in African-American and sub-saharan populations. A downward gradient of dry ear wax allele phenotypes can be drawn from northern China to southern Asia and a downward gradient can also be drawn from eastern Siberia to western Europe. The allele frequencies within ethnicities continued to be maintained because the ABCC11 gene is inherited as a haplotype, a group of genes or alleles that tend to be inherited as a single unit.