Ribosome profiling unveils unannotated sequences in yeast translation

A recent study has uncovered extensive translation in Saccharomyces cerevisiae, with the majority of elements, including 19,000 noncanonical ones, lacking conservation as protein-coding genes. This suggests their role in rapidly evolving genotype-phenotype connections. The research was conducted by Dr. Anne-Ruxandra Carvunis and her team at the University of Pittsburgh and published in Cell Systems.

According to the findings of ribosome profiling experiments, there is widespread translation of previously unannotated sequences, raising questions about their biological significance. The study identified thousands of such sequences in yeast, revealing that almost none exhibit evolutionary conservation. Despite this lack of conservation, the researchers used microscopy to detect unannotated proteins, some of which were found to confer fitness benefits. These findings illuminate the complex relationship between translation, sequence conservation, and the functional aspects of previously unrecognized protein-coding elements.

The process of translation involves ribosomes synthesizing proteins. Ribosome profiling experiments have revealed that many short sequences previously considered noncoding are actively translated. To identify protein-coding genes within this noncanonical translatome, the researchers employed a comprehensive framework known as iRibo along with high-powered selection inferences for short sequences. The resulting reference translatome for Saccharomyces cerevisiae comprised 5,400 canonical and nearly 19,000 noncanonical translated elements. Interestingly, only 14 noncanonical elements showed detectable purifying selection. A subset of translated elements without selection signatures was found to be involved in biological processes such as DNA repair, stress response, and post-transcriptional regulation. These discoveries suggest that most translated elements may not be conserved protein-coding genes but play roles in genotype-phenotype relationships through rapidly evolving molecular mechanisms.

In conclusion, this research highlights the complexity of the translated genomic landscape. It emphasizes that while most translated elements may lack evolutionary conservation, they contribute to genotype-phenotype relationships through diverse and rapidly evolving molecular mechanisms. The study's integration of advanced profiling techniques provides insights into the functional aspects of previously overlooked protein-coding elements.

Cell Press: Aaron Wacholder, et al., A vast evolutionarily transient translatome contributes to phenotype and fitness, Cell Systems (May 2023). DOI: https://doi.org/10.1016/j.cels.2023.04.002