title: Are Human Translated Pseudogenes Functional?
abstract: By definition, pseudogenes are relics of former genes that no longer possess biological functions. Operationally, they are identified based on disruptions of open reading frames (ORFs) or presumed losses of promoter activities. Intriguingly, a recent human proteomic study reported peptides encoded by 107 pseudogenes. These peptides may play currently unrecognized physiological roles. Alternatively, they may have resulted from accidental translations of pseudogene transcripts and possess no function. Comparing between human and macaque orthologs, we show that the nonsynonymous to synonymous substitution rate ratio (ω) is significantly smaller for translated pseudogenes than other pseudogenes. In particular, five of 34 translated pseudogenes amenable to evolutionary analysis have ω values significantly lower than 1, indicative of the action of purifying selection. This and other findings demonstrate that some but not all translated pseudogenes have selected functions at the protein level. Hence, neither ORF disruption nor presence of protein product disproves or proves gene functionality at the protein level.
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor jianzhi@umich.edu.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D023281:Genomics / Q000379:methods; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D020543:Proteome; D011544:Pseudogenes / Q000235:genetics*; D012641:Selection, Genetic; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D020543:Proteome
keywords: macaque; nonsynonymous substitution rate; purifying selection; synonymous substitution rate; transcription; translation