The Long History of the Diverse Roles of Short ORFs: sPEPs in Fungi.

Since the completion of the genome sequence of the model eukaryote Saccharomyces cerevisiae, there have been significant advancements in the field of genome annotation, in no small part due to the availability of datasets that make large-scale comparative analyses possible. As a result, since its completion there has been a significant change in annotated ORF size distribution in this first eukaryotic genome, especially in short ORFs (sORFs) predicted to encode polypeptides less than 150 amino acids in length. Due to their small size and the difficulties associated with their study, it is only relatively recently that these genomic features and the sORF-encoded peptides (sPEPs) they encode have become a focus of many researchers. Yet while this class of peptides may seem new and exciting, the study of this part of the proteome is nothing new in S. cerevisiae, a species where the biological importance of sPEPs has been elegantly illustrated over the past 30 years. Here the authors showcase a range of different sORFs found in S. cerevisiae and the diverse biological roles of their encoded sPEPs, and provide an insight into the sORFs found in other fungal species, particularly those pathogenic to humans.