PT - JOURNAL ARTICLE AU - Sondos Samandi AU - Annie V. Roy AU - Vivian Delcourt AU - Jean-François Lucier AU - Jules Gagnon AU - Maxime C. Beaudoin AU - Benoît Vanderperre AU - Marc-André Breton AU - Julie Motard AU - Jean-François Jacques AU - Mylène Brunelle AU - Isabelle Gagnon-Arsenault AU - Isabelle Fournier AU - Aida Ouangraoua AU - Darel J. Hunting AU - Alan A. Cohen AU - Christian R. Landry AU - Michelle S. Scott AU - Xavier Roucou TI - Deep transcriptome annotation suggests that small and large proteins encoded in the same genes often cooperate AID - 10.1101/142992 DP - 2017 Jan 01 TA - bioRxiv PG - 142992 4099 - http://biorxiv.org/content/early/2017/09/22/142992.short 4100 - http://biorxiv.org/content/early/2017/09/22/142992.full AB - Recent studies in eukaryotes have demonstrated the translation of alternative open reading frames (altORFs) in addition to annotated protein coding sequences (CDSs). We show that a large number of small proteins could in fact be coded by altORFs. The putative alternative proteins translated from altORFs have orthologs in many species and evolutionary patterns indicate that altORFs are particularly constrained in CDSs that evolve slowly. Thousands of predicted alternative proteins are detected in proteomic datasets by reanalysis using a database containing predicted alternative proteins. Protein domains and co-conservation analyses suggest a potential functional relationship between small and large proteins encoded in the same genes. This is illustrated with specific examples, including altMiD51, a 70 amino acid mitochondrial fission-promoting protein encoded in MiD51/Mief1/SMCR7L, a gene encoding an annotated protein promoting mitochondrial fission. Our results suggest that many coding genes code for more than one protein that are often functionally related.