Preprint: genome-scale CRISPR base editing measures functional effects of 308,000 yeast variants

Researchers have posted a preprint on bioRxiv describing a genome-scale CRISPR base-editing experiment in the yeast Saccharomyces cerevisiae. The team introduced 308,461 single-nucleotide variants spanning both coding and non-coding regions of the genome, then measured each variant's effect on cellular growth.

Of the variants tested, 18,009 showed statistically significant effects: 17,784 reduced growth and 225 increased it. The study found that variant effects correlated with functional consequence (e.g. synonymous versus missense), gene essentiality, evolutionary conservation, and predicted protein structure — consistent with expectations from population genetics, but demonstrated here at unusually large scale in a controlled experimental setting.

For non-coding variants, the screen revealed positions critical for RNA splicing and other RNA-level functions. The authors suggest their approach can produce experimentally grounded estimates of variant effect size that could inform computational variant interpretation frameworks, including those trained on evolutionary conservation or protein language models.

This work has not yet been peer-reviewed. Yeast is a widely used model organism in genetics, but variant effects observed in yeast may not translate directly to human biology. The scale of the screen — and the integration of functional data with structural and evolutionary features — represents a methodological contribution to the broader effort to interpret the consequences of genetic variation across genomes.