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Title: Genome-wide association studies identify heavy metal ATPase3 as the primary determinant of natural variation in leaf cadmium in Arabidopsis thaliana

item CHAO, DAI-YIN - University Of Aberdeen
item SILVA, ADRIANO - Purdue University
item Baxter, Ivan
item HUANG, YU - University Of California
item NORDBORG, MAGNUS - Gregor Mendel Institute
item DANKU, JOHN - University Of Aberdeen
item LAHNER, BRETT - Purdue University
item YAKUBOVA, ELENA - Purdue University
item SALT, DAVID - University Of Aberdeen

Submitted to: PLoS Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/13/2012
Publication Date: 9/6/2012
Citation: Chao, D., Silva, A., Baxter, I.R., Huang, Y., Nordborg, M., Danku, J., Lahner, B., Yakubova, E., Salt, D. 2012. Genome-wide association studies identify heavy metal ATPase3 as the primary determinant of natural variation in leaf cadmium in Arabidopsis thaliana. PLoS Genetics. 8(9):e1002923.

Interpretive Summary: Cadmium (Cd) is a potentially toxic metal pollutant that threatens food quality and human health in many regions of the world. Plants have evolved mechanisms for the acquisition of essential metals such as zinc and iron from the soil. Though often quite specific, such mechanisms can also lead to the accumulation of Cd by plants. Understanding natural variation in the processes that contribute to Cd accumulation in food crops could help minimize the human health risk posed. We have discovered that DNA sequence changes at a single gene, which encodes the heavy metal ATPase 3 (HMA3), drives the variation in Cd accumulation we observe in a world-wide sample of Arabidopsis thaliana. We identified seven major HMA3 variants, of which three contribute to reduce Cd accumulation in leaves of A. thaliana. This knowledge will allow us to target this particular gene for crop improvement and to develop healthy food crops.

Technical Abstract: Understanding the mechanism of cadmium (Cd) accumulation in plants is important to help reduce its potential toxicity to both plants and humans through dietary and environmental exposure. Here, we report a study to uncover the genetic basis underlying natural variation in Cd accumulation in a world-wide collection of 349 wild collected Arabidopsis thaliana accessions. We identified a 4-fold variation (0.5 – 2 µg Cd g-1 dry weight) in leaf Cd accumulation when these accessions were grown in a controlled common garden. By combining genome-wide association mapping, linkage mapping in an experimental F2 population and transgenic complementation, we reveal that variation at the AtHMA3 locus is responsible for 38% of the total variation in leaf Cd accumulation we observe in this diverse population of A. thaliana accessions. Analysis of the predicted amino acid sequence of AtHMA3 from 82 A. thaliana accessions reveals the existence of seven major natural protein coding haplotypes. Association of these haplotypes with leaf cadmium accumulation suggests that three of these haplotypes are active and four are inactive, and that elevated leaf Cd accumulation is associated with the reduced function of AtHMA3.