The "bare" appearance of human skin is a trait that distinguishes humans from all other primates. This striking appearance results from miniaturized body hair and increased sweat gland density (approximately 10 times higher than that of a chimpanzee). These adaptations allow humans to cool their body temperature through increased air flow over the skin and evaporation of water from the skin surface. This project will find and explain the genomic changes underlying the human-specific evolutionary modifications to hair and sweat gland composition. The biological insights, as well as the data, methods and tools developed as part of this research program, will provide novel assets to transform the investigation of the genetic bases of other adaptive skin traits and skin physiology more generally. The data generated by this project also will advance ongoing efforts to build and properly pattern hair and eccrine glands in vitro, a major obstacle in comprehensive human skin regeneration. In addition, this project will support the training of under-represented minority students and researchers, and fund the development of a public, educational website on human skin evolution, which will highlight outstanding questions in skin evolution and curate ongoing and new discoveries on this topic.
This research program builds on the recent discovery by the research team that a subset of biological signals that increase eccrine gland density also alter hair development, leading to diminished hair size. The working hypothesis of this project is that humans have acquired evolutionary mutations in regulatory sequences leading to concomitantly increased eccrine gland density and diminished hair size relative to other primates. The researchers will (i) map out the regulatory sequences, or enhancers, that control the expression of a key developmental factor, En1, that reciprocally regulates eccrine sweat gland density and hair size; (ii) define the genomic changes within these enhancers that contributed to unique hair and sweat gland traits in humans, by investigating the functional significance of human-specific changes using genome edited mouse models of diverged human and chimpanzee regulatory sequences.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
