Evolution of metal hyperaccumulation required cis-regulatory changes and triplication of HMA4
Abstract
Little is known about the types of mutations underlying the evolution of species-specific traits. The metal hyperaccumulator Arabidopsis halleri has the rare ability to colonize heavy-metal-polluted soils, and, as an extremophile sister species of Arabidopsis thaliana, it is a powerful model for research on adaptation. A. halleri naturally accumulates and tolerates leaf concentrations as high as 2.2% zinc and 0.28% cadmium in dry biomass. On the basis of transcriptomics studies, metal hyperaccumulation in A. halleri has been associated with more than 30 candidate genes that are expressed at higher levels in A. halleri than in A. thaliana. Some of these genes have been genetically mapped to broad chromosomal segments of between 4 and 24 cM co-segregating with Zn and Cd hypertolerance. However, the in planta loss-of-function approaches required to demonstrate the contribution of a given candidate gene to metal hyperaccumulation or hypertolerance have not been pursued to date. Using RNA interference to downregulate HMA4 (HEAVY METAL ATPASE 4) expression, we show here that Zn hyperaccumulation and full hypertolerance to Cd and Zn in A. halleri depend on the metal pump HMA4. Contrary to a postulated global trans regulatory factor governing high expression of numerous metal hyperaccumulation genes, we demonstrate that enhanced expression of HMA4 in A. halleri is attributable to a combination of modified cis-regulatory sequences and copy number expansion, in comparison to A. thaliana. Transfer of an A. halleri HMA4 gene to A. thaliana recapitulates Zn partitioning into xylem vessels and the constitutive transcriptional upregulation of Zn deficiency response genes characteristic of Zn hyperaccumulators. Our results demonstrate the importance of cis-regulatory mutations and gene copy number expansion in the evolution of a complex naturally selected extreme trait. The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils and for bio-fortification.
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Hyperaccumulators result in overexpression of transporters such as AhHMA4, in xylem parenchyma and pericycle of the root, and in A. halleri shoot tissues viz., cambium and xylem parenchyma.
“Hyperaccumulators result in overexpression of transporters such as AhHMA4, in xylem parenchyma and pericycle of the root, and in A. halleri shoot tissues viz., cambium and xylem parenchyma (Hanikenne et al., 2008).”
From Plant hyperaccumulators: a state-of-the-art review on mechanism of heavy metal transport and sequestration (2025) · cites this paper as Hanikenne et al., 2008
Comparative expression analysis reported that later genomic evolution was displayed by the enhanced copy number of transporters such as HMA4 to 3 and MTP1 to 5 in Arabidopsis halleri compared to single-copy found in wild-type A. thaliana.
“A comparative expression analysis reported that later genomic evolution was displayed by the enhanced copy number of transporters such as; HMA4 to 3 and MTP1 to 5 in Arabidopsis halleri compared to single-copy found in wild-type A. thaliana (Hanikenne et al., 2008; Shahzad et al., 2010).”
From Plant hyperaccumulators: a state-of-the-art review on mechanism of heavy metal transport and sequestration (2025) · cites this paper as Hanikenne et al., 2008
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- Authors
- Hanikenne, M., Talke, I. N., Haydon, M. J., Lanz, C., Nolte, A., Motte, P., Kroymann, J., Weigel, D., & Krämer, U.
- Affiliations
- Max Planck Institute of Molecular Plant Physiology (DE)
- Max Planck Institute for Developmental Biology (DE)
- Max Planck Institute for Chemical Ecology (DE)
- Corresponding author
- Krämer, Ute
- Venue
- Nature
- Published
- 2008-04-20
- Volume
- 453
- Issue
- 7193
- Pages
- 391-395
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2039071784
- Cited by
- 812
- References
- 45
- Citations by year
- 2026: 33 · 2025: 28 · 2024: 31 · 2023: 28 · 2022: 44 · 2021: 50 · 2020: 55 · 2019: 43 · 2018: 46 · 2017: 33 · 2016: 54 · 2015: 41 · 2014: 50 · 2013: 49 · 2012: 53
- FWCI
- 57.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- ORBi (University of Liège) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Pollution › Heavy metals in environment
- Physical Sciences › Chemistry › Analytical Chemistry › Heavy Metals in Plants
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- metal hyperaccumulation, HMA4, heavy metal ATPase, Arabidopsis halleri, cis-regulatory elements, gene copy number expansion, zinc hyperaccumulation, cadmium tolerance, metal transporters, bioremediation, metal-contaminated soil, RNAi knockdown, transposable elements, transposable element insertion
- MeSH terms
- Adaptation, Physiological, Adenosine Triphosphatases, Cadmium, Metals, Molecular Sequence Data, Organ Specificity, Promoter Regions, Genetic, Transcription, Genetic, Zinc, Arabidopsis, Gene Expression Regulation, Plant, Gene Dosage, Genome, Plant, Evolution, Molecular, Arabidopsis Proteins, RNA Interference
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