The ambush hypothesis at the whole-organism level: Off frame, ‘hidden’ stops in vertebrate mitochondrial genes increase developmental stability

Off frame reading of protein coding sequences reveals numerous stop codons. The genetic code and genomic codon usages maximize hidden stop numbers, minimizing effects of ribosomal slippages. This increases efficiency and homogeneity of protein expression. Here I test whether developmental stability in bilateral morphological traits of lizards and primates increases with numbers of hidden stops in mitochondrial protein coding genes. Expected effects are weak, but are apparent in 14 among 16 independent taxonomic groups for the non-coding +1 frame, and 12 among 16 for the −1 frame. Results stress that many molecular factors determine phenotypes in a complex manner, frequently undetectable by classical quantitative genetics. Explicit molecular hypotheses can partially palliate this shortcoming, and uncover unsuspected links between genotype and phenotype, especially when molecular epistasis (here interactions between hidden stops and ribosomes), is involved. Effects of hidden stops on morphological developmental stability suggest that mitochondrial off frame stops might also affect human cumulative neurodegenerative diseases. Results suggest adaptive rather than neutralist interpretations of the ambush hypothesis.