Revisiting the Saccharomyces cerevisiae predicted ORFeome
Abstract
Accurately defining the coding potential of an organism, i.e. all protein-encoding open reading frames (ORFs) or "ORFeome" is a prerequisite to fully understand its biology. ORFeome annotation involves iterative computational predictions from genome sequences combined with experimental verifications. Here we re-examine a set of Saccharomyces cerevisiae "orphan" ORFs recently removed from the original ORFeome annotation due to lack of conservation across evolutionarily related yeast species. We show that many orphan ORFs produce detectable transcripts and/or translated products in various functional genomics and proteomics experiments. Combining a naive Bayes model that predicts the likelihood of an ORF to encode a functional product with experimental verification of strand-specific transcripts, we argue that orphan ORFs should remain as candidates for functional ORFs. In support of this model, inter-strain intra-species genome sequence variation is lower across orphan ORFs than in intergenic regions, indicating that orphan ORFs endure functional constraints and resist deleterious mutations. We conclude that ORFs should be evaluated based on multiple levels of evidence and not be removed from ORFeome annotation solely based on low sequence conservation in other species. Rather, such ORFs might be important for micro-evolutionary divergence between species.
Footnotes
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- Received January 29, 2008.
- Accepted May 5, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
