Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease.

ABSTRACT: The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. The yeast gene SEC53 encodes a homolog of human PMM2. We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. We find that after 1000 generations, most populations compensate for the slow-growth phenotype associated with the sec53 human-disease-associated alleles. Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with

SUBMITTER: Vignogna RC 

PROVIDER: S-EPMC9578706 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature