Flowering plants (angiosperms) can grow at extreme altitudes, and have been observed growing as high as 6,400 metres above sea level1,2; however, the molecular mechanisms that enable plant adaptation specifically to altitude are unknown. One distinguishing feature of increasing altitude is a reduction in the partial pressure of
oxygen (pO2). Here we investigated the relationship between altitude and
oxygen sensing in relation to
chlorophyll biosynthesis-which requires molecular oxygen3-and
hypoxia-related gene expression. We show that in etiolated seedlings of angiosperm species, steady-state levels of the phototoxic
chlorophyll precursor
protochlorophyllide are influenced by sensing of atmospheric
oxygen concentration. In Arabidopsis thaliana, this is mediated by the PLANT
CYSTEINE OXIDASE (PCO) N-degron pathway substrates GROUP VII
ETHYLENE RESPONSE
FACTOR transcription factors (ERFVIIs). ERFVIIs positively regulate expression of FLUORESCENT IN BLUE LIGHT (FLU), which represses the first committed step of
chlorophyll biosynthesis, forming an inactivation complex with
tetrapyrrole synthesis
enzymes that are negatively regulated by ERFVIIs, thereby suppressing
protochlorophyllide. In natural populations representing diverse angiosperm clades, we find
oxygen-dependent altitudinal clines for steady-state levels of
protochlorophyllide, expression of inactivation complex components and
hypoxia-related genes. Finally, A. thaliana accessions from contrasting altitudes display altitude-dependent ERFVII activity and accumulation. We thus identify a mechanism for genetic adaptation to absolute altitude through alteration of the sensitivity of the
oxygen-sensing system.