Unraveling the genetic jumps that shaped skin and skin cancer risk


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, with relative timing and pigmentation effects of each SVA insertion highlighted. Ancestral hominids and many extant great apes have light skin pigmentation, with UV protection conferred by denser body hair. Early human evolution involved increasing pigmentation and decreasing body hair. The ancient SVA F retrotransposon, which is shared by Neanderthals with modern humans on all continents, may have inserted during this period into the ASIP intron—decreasing ASIP expression and increasing pigmentation—and became fixed in Homo sapiens. Much more recently, a subsequent SVA F1 insertion appeared and expanded in frequency (to several percent) within ancestral European populations, increasing ASIP expression and decreasing pigmentation.

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