Ambush hypothesis

The ambush hypothesis is a hypothesis in the field of molecular genetics that suggests that the prevalence of “hidden” or off-frame stop codons in DNA selectively deters off-frame translation of mRNA to save energy, molecular resources, and to reduce strain on biosynthetic machinery by truncating the production of non-functional, potentially cytotoxic protein products.

[1] Typical coding sequences of DNA lack in-frame internal stop codons to avoid the premature reduction of protein products when translation proceeds normally.

Observations that the number of off-frame stop codons is positively correlated with the expression level of a gene support the ambush hypothesis by increasing translational regulation (hidden stop frequency) to discourage off-frame reading in genes that are expressed at a high level.

[5][6] The positive correlation indicates that the off-frame translation of larger genes with higher expression levels likely costs a cell more energy, resources, and pathway efficiency than translating smaller, more rare genes in a shifted reading frame.

[1] Off-frame stop codon frequency is negatively correlated with gestation time in primates and though there are many factors that link molecular translational efficiency to the rate of morphogenesis, these findings suggests that not only individual cells but entire organisms may benefit from the development of hidden stop codons to effectively halt off-frame synthesis.