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A vast evolutionarily transient translatome contributes to phenotype and fitness

Aaron Wacholder, Saurin Bipin Parikh, Nelson Castilho Coelho, Omer Acar, Carly Houghton, Lin Chou, Anne‐Ruxandra Carvunis

2023Cell Systems65 citationsDOIOpen Access PDF

Abstract

Translation is the process by which ribosomes synthesize proteins. Ribosome profiling recently revealed that many short sequences previously thought to be noncoding are pervasively translated. To identify protein-coding genes in this noncanonical translatome, we combine an integrative framework for extremely sensitive ribosome profiling analysis, iRibo, with high-powered selection inferences tailored for short sequences. We construct a reference translatome for Saccharomyces cerevisiae comprising 5,400 canonical and almost 19,000 noncanonical translated elements. Only 14 noncanonical elements were evolving under detectable purifying selection. A representative subset of translated elements lacking signatures of selection demonstrated involvement in processes including DNA repair, stress response, and post-transcriptional regulation. Our results suggest that most translated elements are not conserved protein-coding genes and contribute to genotype-phenotype relationships through fast-evolving molecular mechanisms.

Topics & Concepts

BiologyRibosome profilingNegative selectionGenePhenotypeSaccharomyces cerevisiaeComputational biologyRibosomeGeneticsTranslation (biology)Coding regionMessenger RNAGenomeRNARNA and protein synthesis mechanismsRNA Research and SplicingGenomics and Phylogenetic Studies
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