The yeast knockout collection (YKO) is a systematic set of Saccharomyces cerevisiae strains in which nearly every non-essential open reading frame has been precisely deleted and replaced with a molecular barcode, enabling parallel functional genomics (Giaever et al., Nature 2002). This resource has become a cornerstone for dissecting gene function, genetic pathways, and the molecular mechanisms that sustain genome stability and cellular homeostasis.
My research has leveraged the YKO to investigate the interplay between gene loss, DNA repair pathways, and genome maintenance. In particular, I co-led a comprehensive re-sequencing of nearly the entire homozygous diploid YKO (4,732 strains), reported in Nature (Puddu et al., 2019). This study provided the first genome-wide view of how deletion of non-essential genes reshapes genome architecture, uncovering pervasive chromosomal rearrangements, copy-number changes, and mitochondrial genome instability. Furthermore, it revealed adaptive trajectories by which knockout strains remodel their genomes to buffer against essential pathway disruption.
Together with the original YKO resource, our genomic characterization provide complementary layers of insight: the deletion collection enables systematic perturbation, while high-resolution genomic profiling uncovers both direct and emergent consequences of gene loss. This dual approach has significantly advanced our understanding of genome plasticity and the robustness of eukaryotic cellular systems.
Key References
- Giaever G., Chu A.M., Ni L. et al. (2002). Functional profiling of the Saccharomyces cerevisiae genome. Nature 418, 387–391.
- Puddu F., Herzog M., Selivanova A., et al. (2019). Genome architecture and stability in the Saccharomyces cerevisiae knockout collection. Nature 573, 416–420.