Comparison of linkage and association mapping in MAGIC lines identifies <i>AtMTP3</i> as a new gene controlling natural variation in leaf zinc concentration in Arabidopsis

The Arabidopsis thaliana MAGIC lines are the result of extensive recombination among 19 accessions, which allows a direct comparison of association and linkage mapping using the same population. We used both approaches to map the genetic basis of natural variation in the leaf ionome of A. thaliana. We found 57 quantitative trait loci (QTL) and 10 significant associations, eight of which co-locate with QTL analysis. This suggests that the genome-wide association has a low rate of false positives in these MAGIC lines, but an overall lower power to identify potential genetic factors explaining natural variation. We replicated several loci previously identified by linkage or association studies and identified new candidate genes. We demonstrated the success of this approach by validating AtMTP3 (a vacuolar zinc and cobalt transporter) as the cause of natural variation in zinc leaf concentration. We showed that Kn-0, one of the MAGIC lines founder accessions, carries a rare AtMTP3 allele that results in increased zinc concentration in leaves. Yeast mutant complementation suggests that Kn-0 AtMTP3 encodes a hypofunctional protein compared with Col-0. Our work demonstrates that natural variation in Zn leaf concentration is linked to vacuolar transport and Zn sequestration in roots, opening up new avenues to manipulate Zn concentration in plants.