Joshua M Akey | PubMed Health

PubMed2026

CYClones: a highly powered, fully genotyped, eight-parent yeast mapping population.

The budding yeast Saccharomyces cerevisiae is a remarkably adaptable organism that thrives in diverse environments. Global sequencing of natural isolates has revealed extensive genetic diversity within the species. Here, we describe the construction and characterization of CYClones (Collaborative Yeast Cross clones), a library of 11,392 segregants generated from a multiparent funnel cross of eight genetically diverse parental strains. To enable the genetic dissection of complex traits, we imputed whole-genome sequences for all segregants and show that CYClones captures a substantial fraction of the global genetic diversity of S. cerevisiae. Haplotype representation is well maintained, with each parental haplotype present at >5% frequency across >95% of the genome. Simulations demonstrate that CYClones has ≥95% power to detect variants with heritability as low as 0.36%, with mapping resolution often finer than the length of a single gene. In summary, CYClones is a powerful community resource for dissecting the genetic architecture of complex and quantitative traits, uncovering context-dependent mutational effects, and identifying causal variants underlying phenotypic diversity.

Saccharomyces cerevisiae↗

PubMed2026

Pervasive context-dependent effects in the genetic architecture of complex and quantitative traits revealed by a powerful multiparent mapping population in yeast.

The genetic dissection of complex traits remains a major challenge in basic and biomedical research, but is essential for understanding the molecular pathways that shape phenotypic variation and for developing predictive models of trait and disease susceptibility. Here, we leverage a novel multiparent mapping population of budding yeast, CYClones, comprising 9,344 haploid strains derived from eight genetically diverse founders (~270,000 SNVs, ~ 1 per 44 bp, capturing 56% of common variants and 32% of all variants with a minor allele frequency greater than 0.005 in the global population), to identify quantitative trait loci (QTL) and systematically investigate the genetic architecture of growth rates across ten environmental conditions. In total, we identified 349 QTL (ranging from 18 to 49 QTL per growth condition) that explained between 60% and 100% of narrow sense heritability across traits. The high power and resolution of CYClones revealed that growth traits exhibited distinct, condition-specific genetic architectures with extensive allelic heterogeneity, where a QTL was the result of multiple tightly linked causal variants. We also observed pleiotropy among QTL with complex, trait-dependent allele effects that are also consistent with allelic heterogeneity. Genetic complexity varied widely, with some traits showing nearly Mendelian architectures, while others were highly polygenic. Introgressed loci played a prominent role in the landscape of growth rate QTL, including a QTL localized to a 2.4 kb interval in the PCA1 cadmium transporter that explains 72% of variation in cadmium resistance and is largely driven by an introgression, and a non-additive interaction between the GAL3 regulator and introgressed GAL1/7/10 alleles, extending a previously described three-locus GAL-pathway incompatibility to a four-locus interaction. In both cadmium and galactose conditions, we show that allelic variation at a small number of loci stratifies the population into regulatory or physiological subgroups, each with distinct genetic architectures, a specific manifestation of epistasis we term allele-dependent stratification. Collectively, our results provide novel insights into the genetics of growth rates in budding yeast, the architectural features of genetic complexity, and demonstrate that CYClones is a powerful platform for revealing the molecular basis of complex trait variation.

Quantitative Trait Loci↗