Selection at the GSDMC locus in horses and its implications for human mobility

Horsepower revolutionized human history through enhanced mobility, transport, and warfare. However, the suite of biological traits that reshaped horses during domestication remains unclear. We scanned an extensive horse genome time series for selection signatures at 266 markers associated with key traits. We detected a signature of positive selection at ZFPM1 —known to be a modulator of behavior in mice—occurring ~5000 years ago (ya), suggesting that taming was one of the earliest steps toward domestication of horses. Intensive selection at GSDMC began ~4750 ya with the domestication bottleneck, leading regulatory variants to high frequency by ~4150 ya. GSDMC genotypes are linked to body conformation in horses and to spinal anatomy, motor coordination, and muscular strength in mice. Our results suggest that selection on standing variation at GSDMC was crucial for the emergence of horses that could facilitate fast mobility in human societies ~4200 ya.