Divergent <i>C. elegans</i> toxin alleles are suppressed by distinct mechanisms

Toxin-antidote elements (TAs) are selfish DNA sequences that favor their transmission to future generations. These TAs consist of two linked genes: a toxin and an antidote. The toxin kills progeny lacking the TA, while the antidote neutralizes the toxin in TA-bearing progeny. Research on Caenorhabditis elegans has identified two TA models: peel-1/zeel-1 and sup-35/pha-1.

A novel TA has been discovered, existing in three different forms within the C. elegans population. The original TA, found in Hawaiian isolates, contains two genes encoding a toxin (TMRL-1) deposited by the mother and an antidote (AMRL-1) expressed during embryogenesis. The toxin triggers larval death in embryos lacking the antidote gene.

Another TA variant has lost the toxin gene but still possesses a partially functional antidote. Most C. elegans strains, including the lab strain N2, carry a highly divergent toxin allele that functions but lacks an antidote due to pseudogenization. Multiple lines of evidence indicate that the N2 tmrl-1 allele is likely targeted by piRNAs, resulting in MUT-16-mediated 22G small interfering RNA (siRNA) production and post-transcriptional silencing of the transcript.

This N2 haplotype is the first naturally occurring unlinked toxin-antidote system where the toxin is suppressed post-transcriptionally by endogenous small RNA pathways.