title: Selection for high oridonin yield in the Chinese medicinal plant Isodon (Lamiaceae) using a combined phylogenetics and population genetics approach.
abstract: Oridonin is a diterpenoid with anti-cancer activity that occurs in the Chinese medicinal plant Isodon rubescens and some related species. While the bioactivity of oridonin has been well studied, the extent of natural variation in the production of this compound is poorly known. This study characterizes natural variation in oridonin production in order to guide selection of populations of Isodon with highest oridonin yield. Different populations of I. rubescens and related species were collected in China, and their offspring were grown in a greenhouse. Samples were examined for oridonin content, genotyped using 11 microsatellites, and representatives were sequenced for three phylogenetic markers (ITS, rps16, trnL-trnF). Oridonin production was mapped on a molecular phylogeny of the genus Isodon using samples from each population as well as previously published Genbank sequences. Oridonin has been reported in 12 out of 74 species of Isodon examined for diterpenoids, and the phylogeny indicates that oridonin production has arisen at least three times in the genus. Oridonin production was surprisingly consistent between wild-collected parents and greenhouse-grown offspring, despite evidence of gene flow between oridonin-producing and non-producing populations of Isodon. Additionally, microsatellite genetic distance between individuals was significantly correlated with chemical distance in both parents and offspring. Neither heritability nor correlation with genetic distance were significant when the comparison was restricted to only populations of I. rubescens, but this result should be corroborated using additional samples. Based on these results, future screening of Isodon populations for oridonin yield should initially prioritize a broad survey of all species known to produce oridonin, rather than focusing on multiple populations of one species, such as I. rubescens. Of the samples examined here, I. rubescens or I. japonicus from Henan province would provide the best source of oridonin.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America. eric.sj.harris@gmail.com
authors.forename: Eric S J
authors.initials: ES
authors.lastname: Harris
authors.forename: Shugeng
authors.initials: S
authors.lastname: Cao
authors.forename: Sean D
authors.initials: SD
authors.lastname: Schoville
authors.forename: Chengming
authors.initials: C
authors.lastname: Dong
authors.forename: Wenquan
authors.initials: W
authors.lastname: Wang
authors.forename: Zaiyou
authors.initials: Z
authors.lastname: Jian
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: David M
authors.initials: DM
authors.lastname: Eisenberg
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
mesh_terms: D045786:Diterpenes, Kaurane / Q000096:biosynthesis*; D005828:Genetics, Population / Q000379:methods*; D037602:Isodon / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D010802:Phylogeny; D010946:Plants, Medicinal / Q000737:chemistry* / Q000145:classification / Q000235:genetics
chemical_list: D045786:Diterpenes, Kaurane; C011959:oridonin