1Internal Medicine - Molecular Medicine, Wake Forest School of Medicine, 2Department of Anthropology, Pennsylvania State University
March 28, 2019 , CC Room 26 C
Facultative, rather than constitutive, pigmentation is the primary means through which human skin interacts with the environment. A robust and persistent tan in response to intense summer ultraviolet radiation would offer protection in a seasonally variable environment and could act as a convergent adaptation to high levels of UVR in equatorial regions of the Americas.
We have recently identified several genes associated with increased tanning response and persistence among 91 Mexican Americans with indigenous American and European ancestry. Association with 2950 candidate SNPs within and upstream of KEGG-defined melanogenesis pathway genes was assessed in PLINK while controlling for basal pigmentation and biogeographic ancestry calculated in FRAPPE. All tests were treated as independent, yielding a Bonferoni-corrected α of 5.6x106. SNPs in eight genes were associated with persistence, including two members of the ubiquitous adenylyl cyclase family found on the surface of melanocytes (ADCY8 and ADCY9). Associated SNP rs378200 (C > T) is an eQTL for ADCY9 in unexposed skin based on data from the Genotype-Tissue Expression (GTEx) Consortium (p = 0.0022) with the derived allele associated with a reduction in gene expression. ADCY9 regulates the MC1R-cAMP signaling pathway which plays a critical role in the regulation of melanocyte development and survival.
Our previously work indicates that selection at ADCY9 occurred after the split between East Asian and American populations. Functional studies of adenylyl cyclases suggest that decreased expression may be associated with an increased ability to tan via similar pathways as MC1R variant-associated suppression of tanning response.
This work was support by a Post-PhD Research Grant to E. Quillen from The Wenner-Gren Foundation for Anthropological Research.