Evolution of Skin Pigmentation

Skin pigmentation is a highly complex trait that has been subject to intense natural selection in human populations. This has led to a pigment gradient, where darker skin is selected for at areas exposed to high ultraviolet radiation (UVR), such as equatorial regions, and lighter pigmentation observed at higher latitudes with lower UVR exposure. Remarkably, Africa possesses the greatest variation in skin pigmentation, with the Khoe-San populations of southern Africa having relatively light skin compared to other sub-Saharan African populations, who are about 50% darker. Skin pigmentation is a highly heritable trait, yet much of our current genetic knowledge on pigmentation genetics inadequately explains normal phenotype variation in African populations. This gap in knowledge is a result from differences in architecture across populations and most pigmentation studies focusing on Eurasian, and African American populations. To this end, we are using a genome-wide association approach on the Khoe-San, who harbor the most ancestral alleles and genetic variation globally. We aim to functionally verify pigmentation genes using CRISPR-driven gene knock-outs in zebrafish. This will help identify novel and canonical pigmentation genes, thereby elucidating the complex architecture of this trait