Human Gene Expression Rescues Mevalonate Pathway Defects in Yeast

The mevalonate pathway is a series of reactions that leads to the production of cholesterol in the body. The ergosterol pathway in yeast is very similar to the cholesterol pathway in humans, in fact, four yeast genes in the... [ view full abstract ]

The mevalonate pathway is a series of reactions that leads to the production of cholesterol in the body. The ergosterol pathway in yeast is very similar to the cholesterol pathway in humans, in fact, four yeast genes in the ergosterol pathway have three human homologs. The objective of this research was to determine if functioning human gene homologs could rescue defective yeast genes and restore cellular growth. CRISPR/Cas9 was first used to repress the yeast genes of interest. Plasmids with the human homologs were inserted into yeast, and the two strains, the repressed yeast strains and the humanized strains, were mated. Growth was challenged with drugs that targeted the specific genes, including Atorvastatin (Lipitor); growth of the humanized yeast cells was an indication of rescue. Preliminary results suggest one rescue was successful while the other rescues require additional experimental work before conclusions can be drawn.  This study was part of a major initiative at the Stanford Genome Technology Center to create personalized medicine, where drug therapies are selected based on one’s unique human genome.