title: Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin.
abstract: Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual's gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation.
authors.affiliation: Department of Biology, Stanford University, Stanford California.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kita
authors.affiliation: Department of Biology, Stanford University, Stanford California.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Fraser
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D005787:Gene Frequency; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D012867:Skin / Q000503:physiopathology / Q000528:radiation effects; D012871:Skin Diseases / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D012880:Skin Pigmentation / Q000235:genetics* / Q000528:radiation effects; D013472:Sunlight / Q000009:adverse effects*; D033921:Vesicular Transport Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; C116429:RASSF9 protein, human; C510061:SLC45A2 protein, human; D033921:Vesicular Transport Proteins