Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

Many viruses, especially RNA viruses, have small to modest sized genomes, and have extensively availed of decoding versatility. Though the report (66) that the first identified overlapping gene in an RNA virus (67, 68) required frameshifting for its expression was incorrect (69) , RNA viruses have nevertheless been a rich source of productively utilized frameshifting. However, despite breakthrough discoveries of frameshifting with many retroviruses and plant viruses, and even with intensive study over decades, it is only recently that frameshift utilization has been found in many important small to medium sized RNA viruses. This advance has depended on the development of relatively new comparative genomic algorithms to discern overlapping functional elements embedded within protein-coding sequences (70) (71) (72) . RNA virus sequences diverge rapidly and, for medically or economically important species, there are frequently many sequenced isolates available, enabling (often even within a single virus species) the statistically significant detection of very short overlapping coding sequences and the RNA elements that direct their translation. The advantages compared to earlier algorithms are most obvious when the overlapping ORF is short and so more difficult to discern.