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

摘要: Variation among individuals arises in part from differences DNA sequences, but the genetic basis for variation most traits, including common diseases, remains only partly understood. Many variants influence phenotypes by altering expression level of one or several genes. The effects such can be detected as quantitative trait loci (eQTL). Traditional eQTL mapping requires large-scale genotype and gene data each individual study sample, which limits sample sizes to hundreds both humans model organisms reduces statistical power. Consequently, many are probably missed, especially those with smaller effects. Furthermore, studies use messenger RNA rather than protein abundance measure expression. Studies that have used mass-spectrometry proteomics reported unexpected between QTL (pQTL) same genes, these been even more limited scope. Here we introduce a powerful method identifying yeast Saccharomyces cerevisiae. We single-cell through green fluorescent tags very large populations genetically variable cells, pooled sequencing compare allele frequencies across genome thousands high versus low abundance. applied this 160 genes per previous studies. also observed closer correspondence mRNA given gene. Most were clustered 'hotspots' multiple proteins, some hotspots found half proteins examined. underlie profound on regulatory network provide insights into cell physiology strains.