The interplay of additivity, dominance, and epistasis in a diploid yeast cross

Abstract

We used a double barcoding system to generate and phenotype a panel of ~200,000 diploid yeast segregants that can be partitioned into hundreds of interrelated families. This experimental design enabled the detection of thousands of genetic interactions and many loci whose effects vary across families. Traits were largely specified by a small number of hub loci with major additive and dominance effects, and pervasive epistasis. Genetic background commonly influenced both the additive and dominance effects of loci, with multiple modifiers typically involved. The most prominent dominance modifier was the mating locus, which had no effect on its own. Our findings show that the interplay between additivity, dominance, and epistasis underlies a complex genotype-to-phenotype map in diploids.

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body

“…However, they also diminish surface adhesion and invasion, limiting our insight into these traits. BY and 3S were also engineered to have a genomic landing pad at the neutral YBR209W locus, enabling site-specific integration of barcodes into segregants 28,31,40 .…”

“…The most powerful genetic mapping approach in S. cerevisiae is linkage mapping with large mapping panels of haploid meiotic progeny (segregants) 27,28 . When two haploid isolates are crossed and sporulated, their haploid segregants each receive a unique random combination of alleles from their parents 29 .…”

“…This shuffling of genetic material makes it possible to measure traits of interest in segregants and then link these traits to specific genomic locations (loci) that cause phenotypic differences 30 . Examination of large numbers of segregants provides the statistical power to identify loci explaining most of the heritable differences in traits of interest 27,28 .…”

“…To enable linkage mapping with an S. cerevisiae cross in mice, we generated a panel of haploid segregants with known genotypes and chromosomally-encoded barcodes 28,31 , which were genetically engineered for high-throughput phenotyping as a pool. We mated the lab reference strain (BY) and a haploid derivative of the 322134S clinical isolate (3S) 24 .…”

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body

“…The engineered BY and 3S strains were mated to produce a BY/3S diploid, which was sporulated. To ensure balanced allele frequencies and random multilocus genotypes among segregants, we performed tetrad dissection and randomly chose and barcoded one MATa haploid from each of 822 tetrads using transformation with a random barcode library 28,31,40 ( Supplementary Fig. 1 ).…”