Gene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast

Abstract

Variation in gene copy number can alter gene expression and influence downstream phenotypes; thus copy-number variation (CNV) provides a route for rapid evolution if the benefits outweigh the cost. We recently showed that genetic background significantly influences how yeast cells respond to gene over-expression (OE), revealing that the fitness costs of CNV can vary substantially with genetic background in a common-garden environment. But the interplay between CNV tolerance and environment remains unexplored on a genomic scale. Here we measured the tolerance to gene OE in four genetically distinct Saccharomyces cerevisiae strains grown under sodium chloride (NaCl) stress. OE genes that are commonly deleterious during NaCl stress recapitulated those commonly deleterious under standard conditions. However, NaCl stress uncovered novel differences in strain responses to gene OE. West African strain NCYC3290 and North American oak isolate YPS128 are more sensitive to NaCl stress than vineyard BC187 and laboratory strain BY4743. Consistently, NCYC3290 and YPS128 showed the greatest sensitivities to gene OE. Although most genes were deleterious, hundreds were beneficial when overexpressed – remarkably, most of these effects were strain specific. Few beneficial genes were shared between the NaCl-sensitive isolates, implicating mechanistic differences behind their NaCl sensitivity. Transcriptomic analysis suggested underlying vulnerabilities and tolerances across strains, and pointed to natural CNV of a sodium export pump that likely contributes to strain-specific responses to OE of other genes. Our results reveal extensive strain-by-environment interaction in the response to gene CNV, raising important implications for the accessibility of CNV-dependent evolutionary routes under times of stress.

Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model

“…In all, our study presents a quantitative assessment of aneuploidy cost, in a single strain and controlled environment. Although the principles reported here are likely conserved, the details including precise fitness costs of specific genes and non-genic features, as well as the generalized sensitivity of strains to translational and proteotoxic stress, could vary significantly across strains and conditions 59,103 . An important consideration for future work will be to quantify that variation.…”

Genetic modification of Candida maltosa, a non-pathogenic CTG species, reveals EFG1 function

“…In fact, C. maltosa has orthologs of most of the genes that have been previously associated to virulence in C. albicans. Gene loss in yeasts has been associated to tolerance of varied stresses [83,84], which could be the conditions that C. maltosa is encountering in the industrial environments where it has been isolated. The case of the TLO genes is worth pointing out.…”

Genetic modification ofCandida maltosa, a nonpathogenic CTG species, revealsEFG1function

“…In fact, C. maltosa has orthologs of most of the genes that have been previously associated to virulence in C. albicans . Gene loss in yeasts has been associated to tolerance of varied stresses (Robinson et al, 2023; Steenwyk & Rokas, 2018), which could be the conditions that C. maltosa is encountering in the industrial environments where it has been isolated.…”