Eubacterial plasmids and chromosomes encode multiple killer genes belo
nging to the hok gene family. The plasmid-encoded killer genes mediate
plasmid stabilization by killing plasmid-free cells. This review desc
ribes the genetics, molecular biology, and evolution of the hok gene f
amily. The complicated antisense RNA-regulated control-loop that regul
ates posttranscriptional and postsegregational activation of killer mR
NA translation in plasmid-free cells is described in detail. Nucleotid
e covariations in the mRNAs reveal metastable stem-loop structures tha
t are formed at the mRNA 5' ends in the nascent transcripts. The metas
table structures prevent translation and antisense RNA binding during
transcription. Coupled nucleotide covariations provide evidence for a
phylogenetically conserved mRNA folding pathway that involves sequenti
al dynamic RNA rearrangements. Our analyses have elucidated an intrica
te mechanism by which translation of an antisense RNA-regulated mRNA c
an be conditionally activated. The complex phylogenetic relationships
of the plasmid-and chromosome-encoded systems are also presented and d
iscussed.