Genome-wide Association Mapping Identifies a New Arsenate Reductase Enzyme Critical for Limiting Arsenic Accumulation in Plants

Dai-Yin Chao, Yi Chen, Jiugeng Chen, Shulin Shi, Ziru Chen, Chengcheng Wang, John M Danku, Fang-Jie Zhao, David E Salt

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Inorganic arsenic is a carcinogen, and its ingestion through foods such as rice presents a significant risk to human health. Plants chemically reduce arsenate to arsenite. Using genome-wide association (GWA) mapping of loci controlling natural variation in arsenic accumulation in Arabidopsis thaliana allowed us to identify the arsenate reductase required for this reduction, which we named High Arsenic Content 1 (HAC1). Complementation verified the identity of HAC1, and expression in Escherichia coli lacking a functional arsenate reductase confirmed the arsenate reductase activity of HAC1. The HAC1 protein accumulates in the epidermis, the outer cell layer of the root, and also in the pericycle cells surrounding the central vascular tissue. Plants lacking HAC1 lose their ability to efflux arsenite from roots, leading to both increased transport of arsenic into the central vascular tissue and on into the shoot. HAC1 therefore functions to reduce arsenate to arsenite in the outer cell layer of the root, facilitating efflux of arsenic as arsenite back into the soil to limit both its accumulation in the root and transport to the shoot. Arsenate reduction by HAC1 in the pericycle may play a role in limiting arsenic loading into the xylem. Loss of HAC1-encoded arsenic reduction leads to a significant increase in arsenic accumulation in shoots, causing an increased sensitivity to arsenate toxicity. We also confirmed the previous observation that the ACR2 arsenate reductase in A. thaliana plays no detectable role in arsenic metabolism. Furthermore, ACR2 does not interact epistatically with HAC1, since arsenic metabolism in the acr2 hac1 double mutant is disrupted in an identical manner to that described for the hac1 single mutant. Our identification of HAC1 and its associated natural variation provides an important new resource for the development of low arsenic-containing food such as rice.

Original languageEnglish
Article numbere1002009
JournalPLoS Biology
Issue number12
Publication statusPublished - 2 Dec 2014

Bibliographical note

Funding: We acknowledge support from the US National Institutes of Health ( (grant 2R01GM078536 and 2P4ES007373-19A1 to DES), European Commission ( (grant PCIG9-GA-2011-291798 to DES) and UK Biotechnology and Biological Sciences Research Council ( (grants BB/L000113/1 to DES, and BB/H006303/1 to FJZ) and the Ministry of Education of China ( (grant IRT1256 to FJZ), start-up funds from the Shanghai Institutes for Biological Sciences ( to DYC, the ‘1000 youth talents program’ from the Chinese Central Government ( to DYC, and the Diamond Light Source ( for the provision of synchrotron beamtime (grant SP9505 to FJZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


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