Whole Genome Analysis of 132 Clinical Saccharomyces cerevisiae Strains Reveals Extensive Ploidy Variation.
Budding yeast has undergone several independent transitions from commercial to clinical lifestyles. The frequency of such transitions suggests that clinical yeast strains are derived from environmentally available yeast populations, including commercial sources. However, despite their important role in adaptive evolution, the prevalence of polyploidy and aneuploidy has not been extensively analyzed in clinical strains. In this study, we have looked for patterns governing the transition to clinical invasion in the largest screen of clinical yeast isolates to date. In particular, we have focused on the hypothesis that ploidy changes have influenced adaptive processes. We sequenced 144 yeast strains, 132 of which are clinical isolates. We found pervasive large-scale genomic variation in both overall ploidy (34% of strains identified as 3n/4n) and individual chromosomal copy numbers (36% of strains identified as aneuploid). We also found evidence for the highly dynamic nature of yeast genomes, with 35 strains showing partial chromosomal copy number changes and eight strains showing multiple independent chromosomal events. Intriguingly, a lineage identified to be baker's/commercial derived with a unique damaging mutation in NDC80 was particularly prone to polyploidy, with 83% of its members being triploid or tetraploid. Polyploidy was in turn associated with a >2× increase in aneuploidy rates as compared to other lineages. This dataset provides a rich source of information on the genomics of clinical yeast strains and highlights the potential importance of large-scale genomic copy variation in yeast adaptation.
Department of Genetics, Stanford University, California 94305 Department of Biology, Stanford University, California 94305 Genome Institute of Singapore, Singapore 138672.
Yuan O
0000-0001-9419-6291
YO
Zhu
Department of Genetics, Stanford University, California 94305.
Gavin
0000-0002-1692-4983
G
Sherlock
Department of Biology, Stanford University, California 94305 dpetrov@stanford.edu.
Dmitri A
DA
Petrov
D000220:Adaptation, Biological; D000782:Aneuploidy; D019070:Cell Lineage / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics*; D016681:Genome, Fungal; D023281:Genomics; D009154:Mutation; D011123:Polyploidy; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000472:pathogenicity; D057891:Tetraploidy
adaptation; aneuploidy; ploidy; population sequencing; population structure