Missense mutations in THCAS are associated with Cannabigerol expression in Cannabis sativa L.

The chemical expression of THCA and CBDA has been previously attributed to copy number gains and losses in THCAS and CBDAS. Here we describe an alternative mechanism to ablate THCAS activity in 5 CBG dominant cannabis varietals. Five cannabis cultivars from three unique cultivators surprisingly contain a THCAS gene but also share homozygous Pro333Arg and Ser355Asn mutations in THCAS. Pro333Arg is commonly found in THCAS dominant varietals but is uniquely found in a homozygous state in CBG varietals in conjunction with homozygous Ser355Asn missense mutations. These results hint at convergent evolution in cannabinoid synthesis where selection for and against THCA synthesis has been applied.