RT Journal Article SR Electronic T1 Deep transcriptome annotation suggests that small and large proteins encoded in the same genes often cooperate JF bioRxiv FD Cold Spring Harbor Laboratory SP 142992 DO 10.1101/142992 A1 Sondos Samandi A1 Annie V. Roy A1 Vivian Delcourt A1 Jean-François Lucier A1 Jules Gagnon A1 Maxime C. Beaudoin A1 Benoît Vanderperre A1 Marc-André Breton A1 Julie Motard A1 Jean-François Jacques A1 Mylène Brunelle A1 Isabelle Gagnon-Arsenault A1 Isabelle Fournier A1 Aida Ouangraoua A1 Darel J. Hunting A1 Alan A. Cohen A1 Christian R. Landry A1 Michelle S. Scott A1 Xavier Roucou YR 2017 UL http://biorxiv.org/content/early/2017/05/27/142992.abstract 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 with a database containing predicted alternative proteins. Protein domains and co-conservation analyses suggest potential functional cooperation or shared function 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.