Alternative reading frames are an underappreciated source of protein sequence novelty

Alternative reading frames of protein coding genes are a major contributor to the evolution of novel protein products. Recent studies demonstrating this include examples across the three domains of cellular life and in viruses. Alternative frame sequences both increase the number of trials available for the evolutionary invention of new genes and have unusual properties which may facilitate gene origin. The structure of the standard genetic code contributes to the features and gene-likeness of some alternative frame sequences. These findings have important implications across diverse areas of molecular biology, including for genome annotation, structural biology, and evolutionary genomics.