Environmental stress and phenotypic tradeoff modulate the adaptive potential of novel coding sequences for de novo gene birth

Authors

Chou, L., Coelho, N. C., Parikh, S., Douds, C., Iannotta, J., Wacholder, A., Lee, J., Houghton, C., Carvunis, A.-R.

Abstract

Novel protein-coding genes can emerge de novo from ancestrally noncoding sequences and promote adaptation to environmental stresses. Previous work proposes that pervasive translation of lowly expressed open reading frames (ORFs) in noncoding regions creates a rich reservoir of 'proto-genes,' of which subsequent acquisition of gene-like properties, such as increased expression, may be favored or purged by natural selection depending on their phenotypic impact. However, whether and how environmental conditions affect the phenotypic impact of proto-genes remains unclear. Here, we experimentally simulated proto-gene evolution in Saccharomyces cerevisiae by individually increasing the expression of nearly a thousand de novo ORFs with prior evidence of native translation under osmotic and endoplasmic-reticulum stress and in control environments. High-throughput phenotyping revealed that growth effects of increased expression varied strongly across environments for de novo ORFs. A follow-up screen across 22 diverse environments revealed a robust positive correlation between environmental stress severity and the mean growth effects of increased de novo ORF expression. At the individual level, 5.4% of tested de novo ORFs conferred beneficial phenotypes in at least one environment, and 83.3% of these also caused deleterious effects elsewhere, revealing widespread phenotypic tradeoffs. We demonstrate that increased expression of the de novo translated ORF YLR112W results in increased growth in the presence of rapamycin through general dampening of the growth-repressing transcriptomic response induced by this drug. Together, these findings demonstrate that stress severity shapes the phenotypic consequences of increased proto-gene expression and shed light on tradeoffs and transcriptome remodeling as mechanisms underlying such environmental dependency.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 28 Aug 2026.

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