The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genes are to ‘drive’ their own transmission while simultaneously imposing a fitness cost on their hosts. Such genes occur in a wide variety of taxa, but their molecular mechanisms and evolutionary origins remain poorly understood. Here I characterize the genetic basis and evolutionary maintenance of a novel genic driver in the primarily selffertilizing species, Caenorhabditis elegans.

This drive element is composed a sperm-delivered toxin, peel-1 , and an embryoexpressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome, and in natural populations, they co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein which is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. zeel-1 is expressed transiently in the embryo and encodes a homolog of a ubiquitin-ligase substrate-recognition subunit, fused to a novel six-pass transmembrane domain. When animals carrying the peel-1/zeel-1 element are crossed to animals lacking it, sperm-delivered PEEL-1 acts through paternal-effect in the F1 heterozygote to kill F2 embryos not inheriting zeel-1. This combination of paternal-effect killing and zygotic self-rescue is unprecedented, and it allows the peel-1/zeel-1 element to become over-represented among the progeny of heterozygous sires, even as this element imposes a substantial fitness cost on these animals.

Surprisingly, although the self-promoting activity of peel-1 and zeel-1 is expected to drive these genes to fixation faster than a neutrally evolving locus, the insertion/deletion polymorphism of peel-1 and zeel-1 appears to be unusually ancient. Haplotypes carrying the peel-1/zeel-1 element and haplotypes lacking it exhibit elevated sequence divergence, and population genetic analyses indicate that natural selection is preserving both haplotypes in the population. One likely explanation for this paradox is that peel-1 and zeel-1 are tightly linked to a site under balancing selection, and the tightness of this linkage maintains the peel-1/zeel-1 element in the polymorphic state.

Together, these results demonstrate that the physical linkage between two novel transmembrane proteins has facilitated their co-evolution into a genic driver, but that long-term maintenance of a balanced polymorphism has prevented this driver from reaching fixation.