Self-restrained sex chromosome drive through sequential asymmetric meiosis

Meiotic drivers are selfish genetic elements that bias their own transmission, violating Mendel’s Law of Equal Segregation. It has long been recognized that sex chromosome-linked drivers present a paradox: their success in transmission can severely distort populations’ sex ratio and lead to extinction. How sex chromosome drivers may resolve this paradox remains unknown. Here, we show that D. melanogaster ’s Stellate (Ste) is an X chromosome-linked driver with a self-restraining mechanism that weakens its drive and prevents extinction. Ste protein asymmetrically segregates into Y-bearing cells during meiosis I, subsequently causing their death. Surprisingly, Ste segregates asymmetrically again during meiosis II, sparing half of the Y-bearing spermatids from Ste-induced defects. Our findings reveal a novel class of sex chromosome drivers that resolve the paradox of suicidal success.