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  1. We conducted a meta-analysis of carbon and oxygen isotopes from tree ring chronologies representing 34 species across 10 biomes to better understand the environmental drivers and physiological mechanisms leading to historical changes in tree intrinsic water use efficiency (iWUE), or the ratio of net photosynthesis (Anet) to stomatal conductance (gs), over the last century. We show a ∼40% increase in tree iWUE globally since 1901, coinciding with a ∼34% increase in atmospheric CO2(Ca), although mean iWUE, and the rates of increase, varied across biomes and leaf and wood functional types. While Cawas a dominant environmental driver of iWUE, the effects of increasing Cawere modulated either positively or negatively by climate, including vapor pressure deficit (VPD), temperature, and precipitation, and by leaf and wood functional types. A dual carbon–oxygen isotope approach revealed that increases inAnetdominated the observed increased iWUE in ∼83% of examined cases, supporting recent reports of global increases inAnet, whereas reductions ingsoccurred in the remaining ∼17%. This meta-analysis provides a strong process-based framework for predicting changes in tree carbon gain and water loss across biomes and across wood and leaf functional types, and the interactions between Caand other environmental factors have important implications for the coupled carbon–hydrologic cycles undermore »future climate. Our results furthermore challenge the idea of widespread reductions ingsas the major driver of increasing tree iWUE and will better inform Earth system models regarding the role of trees in the global carbon and water cycles.

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