Nolan Kamitaki, a graduate student in the lab, uncovered how “jumping genes,” known as retrotransposons, have played a surprising role in shaping human traits. While genome-wide association studies identified genetic variation at the ASIP gene as a key player in skin pigmentation, the causal genetic variant remained elusive. We discovered that a family of SVA retrotransposons jumped into ASIP twice and influenced skin color and skin cancer risk. The first jump likely occurred before the separation of modern humans and Neanderthals and decreased ASIP’s abundance, leading to an increase in skin pigmentation. The second jump likely occurred in the ancestors of some modern Europeans and reversed the effect, leading to less pigmentation and increased skin cancer risk. The latter SVA insertion appears to be the functional link between the GWAS locus and skin traits, underscoring the importance of including structural variations in genetic studies to understand how DNA influences physical traits and disease. Read the full story here.

This work was featured in a Nature Genetics News & Views and Veera Rajagopal’s GWAS Stories.

Schematic of the evolution of hair and skin pigmentation in hominid lineages from Fig. 5d of Kamitaki et al.