PT  - JOURNAL ARTICLE
AU  - Wacholder, Aaron
AU  - Parikh, Saurin Bipin
AU  - Coelho, Nelson Castilho
AU  - Acar, Omer
AU  - Houghton, Carly
AU  - Chou, Lin
AU  - Carvunis, Anne-Ruxandra
TI  - A vast evolutionarily transient translatome contributes to phenotype and fitness
AID  - 10.1101/2021.07.17.452746
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2021.07.17.452746
4099  - http://biorxiv.org/content/early/2023/02/02/2021.07.17.452746.short
4100  - http://biorxiv.org/content/early/2023/02/02/2021.07.17.452746.full
AB  - 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. Surprisingly, 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.Competing Interest StatementA.-R.C. is a member of the scientific advisory board for Flagship Labs 69, Inc.