Abstract

Cadmium (Cd) accumulation in tea plants ( Camellia sinensis ) under chronic, nonphytotoxic field conditions poses a persistent food safety challenge; however, the genetic basis of this process remains uncharacterized. To dissect the genetic architecture of this trait, we quantify leaf Cd content and perform genome-wide association studies (GWAS) across 207 diverse tea accessions which have been cultivated for decades. Quantification analysis of Cd content reveals substantial natural variation in Cd content between young leaves (YL) and mature leaves (ML) under nonphytotoxic environment, with 38.2% of the 173 accessions with paired data intrinsically accumulating more Cd in YL than in ML. GWAS identify 112 quantitative trait loci associated with Cd accumulation. By further integrating the results of GWAS with Cd-responsive transcriptome profiling, we prioritize 14 high-confidence candidate genes. One of these candidate genes, CsHIPP6 , which encodes a heavy metal-associated isoprenylated plant protein, is selected for further functional investigation. Heterologous expression in yeast and Arabidopsis demonstrates that CsHIPP6 enhances Cd tolerance and significantly reduces Cd accumulation. Our findings elucidate the genetic architecture underlying long-term Cd accumulation in perennial crops and highlight CsHIPP6 as a valuable target for breeding low-Cd tea cultivars to ensure beverage safety amidst rising environmental contamination.