title: Genome-wide association studies identify heavy metal ATPase3 as the primary determinant of natural variation in leaf cadmium in Arabidopsis thaliana.
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 on 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 HMA3 is the sole major locus responsible for the variation in leaf Cd accumulation we observe in this diverse population of A. thaliana accessions. Analysis of the predicted amino acid sequence of HMA3 from 149 A. thaliana accessions reveals the existence of 10 major natural protein haplotypes. Association of these haplotypes with leaf Cd accumulation and genetics complementation experiments indicate that 5 of these haplotypes are active and 5 are inactive, and that elevated leaf Cd accumulation is associated with the reduced function of HMA3 caused by a nonsense mutation and polymorphisms that change two specific amino acids.
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Dai-Yin
authors.initials: DY
authors.lastname: Chao
authors.forename: Adriano
authors.initials: A
authors.lastname: Silva
authors.forename: Ivan
authors.initials: I
authors.lastname: Baxter
authors.forename: Yu S
authors.initials: YS
authors.lastname: Huang
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordborg
authors.forename: John
authors.initials: J
authors.lastname: Danku
authors.forename: Brett
authors.initials: B
authors.lastname: Lahner
authors.forename: Elena
authors.initials: E
authors.lastname: Yakubova
authors.forename: David E
authors.initials: DE
authors.lastname: Salt
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D002104:Cadmium; D055106:Genome-Wide Association Study; D018515:Plant Leaves / Q000378:metabolism*; D018517:Plant Roots / Q000378:metabolism; D018520:Plant Shoots / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D029681:Arabidopsis Proteins; D002104:Cadmium; D000251:Adenosine Triphosphatases; C494967:HMA2 protein, Arabidopsis; C484509:HMA3 protein, Arabidopsis