Scholarlink

<p>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 <i>Saccharomyces cerevisiae</i> 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 106 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Population-scale chemical response revealed by a barcoded yeast collection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月28日

查看全文
  • Abhishek Dutta,
  • Marion Garin,
  • Victor Loegler,
  • Gauthier Brach,
  • Anne Friedrich,
  • Mami Yoshimura,
  • Hiroyuki Hirano,
  • Hiroyuki Osada,
  • Charles Boone,
  • Yoko Yashiroda,
  • Jing Hou,
  • Joseph Schacherer

摘要

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 106 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.