Population-scale chemical response revealed by a barcoded yeast collection
Abstract
Natural genetic variation shapes how microbial populations adapt to environmental and chemical challenges, but scalable approaches to map genotype-phenotype relationships across diverse genetic backgrounds remain limited. Here, we developed a systematically barcoded collection of 520 Saccharomyces cerevisiae natural isolates that captures the ecological, geographical and genetic diversity of the species. Using pooled barcode sequencing, we profiled fitness responses to over 600 bioactive and natural compounds, revealing broader and more polarized bioactivity than the standard yeast gene-deletion collection. Fitness-based clustering defined six major compound groups with reproducible, population-structured sensitivity patterns. Genome-wide association analysis identified significant genetic variants across 107 compounds, linking natural polymorphisms to chemical responses and involving genes in genome maintenance, ribosome biogenesis, vesicular trafficking and stress tolerance. Together, our barcoded natural population provides a scalable framework for chemical-genetic screening, enabling systematic dissection of how genetic diversity shapes microbial fitness and adaptation.
Related
- Forensic characteristics and genetic variations of Han Chinese population in Shenzhen revealed by 23 autosomal STRs
- Cell-resolved pharmacodynamic profiling reveals tissue- and cell-population-specific activity of antisense oligonucleotide chemical conjugates in vivo
- Chemogenomic profiling of diverse Saccharomyces cerevisiae strains using the novel CRISPR-Cas9 markerless barcoded library BarMix
- Protocol for constructing barcoded Saccharomyces cerevisiae strains and performing pooled mating experiments
- Multiplexed single-molecule analysis of barcoded protein variants
BibTeX
@article{dutta2026populationscale,
title = {{Population-scale chemical response revealed by a barcoded yeast collection}},
author = {Abhishek Dutta and Marion Garin and Victor Loegler and Gauthier Brach and Anne Friedrich and Mami Yoshimura and Hiroyuki Hirano and Hiroyuki Osada and Charles Boone and Yoko Yashiroda and Jing Hou and Joseph Schacherer},
journal = {Nature Communications},
year = {2026},
month = may,
doi = {10.1038/s41467-026-73532-z},
url = {https://hal.science/hal-05760357v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Population-scale chemical response revealed by a barcoded yeast collection
AU - Abhishek Dutta
AU - Marion Garin
AU - Victor Loegler
AU - Gauthier Brach
AU - Anne Friedrich
AU - Mami Yoshimura
AU - Hiroyuki Hirano
AU - Hiroyuki Osada
AU - Charles Boone
AU - Yoko Yashiroda
AU - Jing Hou
AU - Joseph Schacherer
PY - 2026
DA - 2026/05/28
JO - Nature Communications
DO - 10.1038/s41467-026-73532-z
UR - https://hal.science/hal-05760357v1
AB - Natural genetic variation shapes how microbial populations adapt to environmental and chemical challenges, but scalable approaches to map genotype-phenotype relationships across diverse genetic backgrounds remain limited. Here, we developed a systematically barcoded collection of 520 Saccharomyces cerevisiae natural isolates that captures the ecological, geographical and genetic diversity of the species. Using pooled barcode sequencing, we profiled fitness responses to over 600 bioactive and natural compounds, revealing broader and more polarized bioactivity than the standard yeast gene-deletion collection. Fitness-based clustering defined six major compound groups with reproducible, population-structured sensitivity patterns. Genome-wide association analysis identified significant genetic variants across 107 compounds, linking natural polymorphisms to chemical responses and involving genes in genome maintenance, ribosome biogenesis, vesicular trafficking and stress tolerance. Together, our barcoded natural population provides a scalable framework for chemical-genetic screening, enabling systematic dissection of how genetic diversity shapes microbial fitness and adaptation.
SN - 2041-1723
SN - 2041-1723
ER -