The landscape of genetic complexity across 5,700 gene expression traits in yeast

TLDR

Many studies have identified quantitative trait loci that influence heritable traits, yet the principles governing their number, effect sizes, and combined impact remain unclear. The authors aim to characterize the complex genetics underlying the inheritance of thousands of transcript levels in a cross between two Saccharomyces cerevisiae strains. They performed a genome‑wide QTL analysis of transcript abundance in this cross to map loci affecting gene expression. Most QTLs are weak, explaining a median 27 % of variance for highly heritable transcripts, yet 40 % of such transcripts show no detectable QTLs; only 3 % fit single‑locus models, 17–18 % fit one or two loci, and about half require more than five loci, with many transcripts exhibiting transgressive segregation and 16 % revealing interacting loci, highlighting extensive genetic complexity.

Abstract

Many studies have identified quantitative trait loci (QTLs) that contribute to continuous variation in heritable traits of interest. However, general principles regarding the distribution of QTL numbers, effect sizes, and combined effects of multiple QTLs remain to be elucidated. Here, we characterize complex genetics underlying inheritance of thousands of transcript levels in a cross between two strains of Saccharomyces cerevisiae . Most detected QTLs have weak effects, with a median variance explained of 27% for highly heritable transcripts. Despite the high statistical power of the study, no QTLs were detected for 40% of highly heritable transcripts, indicating extensive genetic complexity. Modeling of QTL detection showed that only 3% of highly heritable transcripts are consistent with single-locus inheritance, 17–18% are consistent with control by one or two loci, and half require more than five loci under additive models. Strikingly, analysis of parent and progeny trait distributions showed that a majority of transcripts exhibit transgressive segregation. Sixteen percent of highly heritable transcripts exhibit evidence of interacting loci. Our results will aid design of future QTL mapping studies and may shed light on the evolution of quantitative traits.