Genetics of single-cell protein abundance variation in large yeast populations

TL;DR

This study introduces a new method for measuring single-cell protein levels in large yeast populations, revealing numerous genetic loci influencing protein abundance and their relation to mRNA variation, with implications for understanding genetic regulation.

Contribution

A novel high-throughput approach for identifying genetic loci affecting protein levels at single-cell resolution in yeast.

Findings

Detected many more loci per gene than previous studies.

Found closer correspondence between protein and mRNA loci.

Identified hotspot loci influencing multiple proteins.

Abstract

Many DNA sequence variants influence phenotypes by altering gene expression. Our understanding of these variants is limited by sample sizes of current studies and by measurements of mRNA rather than protein abundance. We developed a powerful method for identifying genetic loci that influence protein expression in very large populations of the yeast Saccharomyes cerevisiae. The method measures single-cell protein abundance through the use of green-fluorescent-protein tags. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci cluster at hotspot locations that influence multiple proteins - in some cases, more than half of those examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell physiology between yeast strains.