Yeast <i>de novo</i> proteins integrate into cellular systems using ancient protein targeting and degradation pathways.

ABSTRACT: Recent evidence demonstrates that eukaryotic genomes encode thousands of evolutionarily novel proteins that originate de novo from non-coding DNA and can contribute to species-specific adaptations. Yet, it remains unclear how these incipient proteins-whose sequences are entirely new to nature-navigate the cellular environment to bring about phenotypic change. Here, we conduct a systematic in vivo investigation of yeast de novo proteins with enhanced growth phenotypes, revealing the early stages of cellular integration. We find that these proteins are strongly enriched at the endoplasmic reticulum (ER) relative to conserved proteins, and that they integrate into cellular systems through conserved membrane targeting, trafficking, and degradation pathways. Despite having

SUBMITTER: Houghton CJ 

PROVIDER: S-EPMC11384008 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature