A Novel Sperm-Delivered Toxin Causes Late-Stage Embryo Lethality and Transmission Ratio Distortion in C. elegans

Abstract

A sperm-delivered toxin and an embryo-expressed antidote form a co-adapted gene complex in C. elegans that promotes its own transmission to the detriment of organisms carrying it.

Abstract

The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome and co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein that is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. In the absence of zeel-1, sperm-delivered PEEL-1 causes lethal defects in muscle and epidermal tissue at the 2-fold stage of embryogenesis. zeel-1 is expressed transiently in the embryo and encodes a novel six-pass transmembrane domain fused to a domain with sequence similarity to zyg-11, a substrate-recognition subunit of an E3 ubiquitin ligase. zeel-1 appears to have arisen recently, during an expansion of the zyg-11 family, and the transmembrane domain of zeel-1 is required and partially sufficient for antidote activity. Although PEEL-1 and ZEEL-1 normally function in embryos, these proteins can act at other stages as well. When expressed ectopically in adults, PEEL-1 kills a variety of cell types, and ectopic expression of ZEEL-1 rescues these effects. Our results demonstrate that the tight physical linkage between two novel transmembrane proteins has facilitated their co-evolution into an element capable of promoting its own transmission to the detriment of organisms carrying it.

Author Summary

Natural selection typically favors only those genetic variants that increase the overall fitness of the organism. Occasionally, however, variants arise that are able to increase their representation in future generations, while simultaneously reducing the fertility or fecundity of their hosts. Although such variants occur in a wide variety of taxa, their genetic bases and molecular mechanisms remain poorly understood. Here we demonstrate that one such variant in the roundworm C. elegans is composed of two adjacent genes: a sperm-delivered toxin and an embryo-expressed antidote. The toxin protein is expressed in sperm and delivered to the embryo upon fertilization. In the presence of the toxin, embryos that don't inherit the antidote gene die during late embryogenesis, whereas those that do develop normally. Both the toxin and the antidote genes encode transmembrane proteins, and both are evolutionarily novel. Our results imply that the tight physical linkage between these two novel genes has facilitated their evolution into a co-adapted gene complex capable of promoting its own transmission to the detriment of host fitness.