rDNA copy number variation alters response to common growth environments in yeast

Abstract

Ribosomal DNA (rDNA) in eukaryotes is maintained in hundreds of copies with significant rDNA copy number variation among individuals within a species. For instance, the rDNA copy number across wild isolates of the budding yeast S. cerevisiae ranges from 90 to 300 copies. We addressed two major questions concerning rDNA copy number variation: (1) why do cells maintain an rDNA copy number in this range and (2) are there functional consequences due to naturally occurring rDNA copy number variation? We investigated the effects of rDNA copy number variation on S. cerevisiae fitness using isogenic strains that have from 35 to 200 rDNA copies. In standard growth conditions, we found that fitness gradually increases with rDNA copy number until a plateau is reached, spanning from 98 to 160 rDNA copies, well within the range observed across diverse S. cerevisiae strains. However, rDNA copy number-dependent fitness differed across environments: strains with higher rDNA copy numbers show greater fitness when presented with stressful conditions. Moreover, the gradual fitness change observed in standard growth conditions gave way to strong threshold effects. Our results suggest that there are selective pressures that drive rDNA array maintenance to a particular copy number and that cells maintain higher rDNA copy numbers to buffer against environmental stress. The similarity of S. cerevisiae rDNA copy number range to the ranges reported in C. elegans, D. melanogaster, and humans suggests that common mechanisms might maintain rDNA copy number across metazoans and warrant further study.