Systematic Discovery of New Genes in the

We used genome-wide comparative analysis of predicted protein sequences to identify many novel small genes, named smORFs for small open reading frames, within the budding yeast genome. Further analysis of 117 of these new genes showed that 84 are transcribed. We extended our analysis of one smORF conserved from yeast to human. This investigation provides an updated and comprehensive annotation of the yeast genome, validates additional concepts in the study of genomes in silico, and increases the expected numbers of coding sequences in a genome with the corresponding impact on future functional genomics and proteomics studies. Current consensus suggests the number of yeast genes to be very close to 6000 (Goffeau et al. 1996; Mewes et al. 1997; Winzeler and Davis 1997). The number of protein-coding genes with open reading frames (ORFs) longer than 100 codons is predicted to be between 5300 and 5400 (Mackiewicz et al. 2002). Two recent studies suggest that the determination of gene numbers by stringent gene identification methods may underestimate the number of genes in human and other organisms (Gopal et al. 2001; Reboul et al. 2001). The initia