Skin is one of the most visible and distinguishing characteristics of humans, and understanding skin variation among humans is of central importance to the field of human biology. Indeed, there have been great advances in the last decade with regards to the genetic and developmental bases of pigmentation of the skin, explaining variation of skin color within and among human populations. However, variation in other important properties of skin, especially its barrier function, has not been well characterized. This proposal uses state-of-the-art genomic approaches to determine the extent and evolutionary relevance of skin barrier variation and address why potentially detrimental variants remain in human populations. The proposed study is at the forefront of applying novel genomic and computational technologies to anthropological questions. Specific courses and workshops are designed within the context of this project to create a major hub for training the next generation of biological anthropologists, both at the undergraduate and graduate levels. In addition, with constant public interaction, the research contributes to a better understanding of how biological evolution of the skin is independent of the cultural constructs of identity.
Recently available modern and ancient genomes allow for a comprehensive look at the evolutionary signatures in the human genome. In addition, long-read sequencing technologies now permit accurate investigation of genomic structural variants (e.g., deletions and duplications of DNA segments), which have an outsized impact on human evolution and biological variation. The proposed study uses these newly available resources to investigate the evolution of the epidermal differentiation complex, a 2Mb region on human chromosome 1, which harbors more than 50 genes with known roles in skin development and function. The genes in this complex are involved in several important functions, such as immune response, insulation from UV light, heat, moisture, and wound healing. Preliminary work indicates the presence of multiple geography-specific adaptive forces, including pathogenic pressures, shaping the genetic variation in this region, providing a glimpse of the evolution of skin barrier function in humans. The proposed project expands on this premise, to provide the most comprehensive understanding to date of the evolutionary forces acting on epidermal differentiation complex genes. In addition, the project identifies genetic variants that are of anthropological significance for human skin phenotypic variation, and are thus perfect targets for downstream functional studies. The project will also lay a methodological groundwork for future anthropological genetic studies, especially pertaining to structural variation in the human genome.
