Superoxide dismutase 1 loss unleashes genome-wide instability in yeast, study finds

A study published in PLOS Genetics by Yang Sui, Dao-Qiong Zheng, and colleagues at institutions including those in the Zheng laboratory has used whole-genome sequencing of Sod1-deficient yeast to reveal the full scale of genomic damage that accumulates when the frontline antioxidant enzyme superoxide dismutase 1 (Sod1) is absent.

In the absence of Sod1, the researchers observed a 13-fold increase in single nucleotide variants, a 12-fold increase in loss of heterozygosity events, a 4-fold increase in chromosomal rearrangements, and a striking 48-fold increase in aneuploidy — gain or loss of whole chromosomes. The breadth of the genomic phenotype indicates that Sod1's role in genome maintenance extends well beyond its classical function of neutralising superoxide radicals.

The study is conducted in a yeast model (Saccharomyces cerevisiae or equivalent), a well-established eukaryotic system for dissecting genome instability mechanisms. While the findings cannot be directly extrapolated to human biology, Sod1 is encoded by a gene with a direct human orthologue; variants in human SOD1 are among the best-characterised causes of familial amyotrophic lateral sclerosis (ALS). The finding that Sod1 loss destabilises the genome at multiple levels may have implications for understanding disease mechanisms beyond classical oxidative stress models, and is relevant to researchers working on genome integrity, cancer biology, and neurodegenerative disease.