ArticlePLoS genetics2020
Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Natural variation suggests candidate genes underlying Caenorhabditis elegans susceptibility to diverse toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Zinc excess promotes lysosome remodeling by activating HLH-30/TFEB through the action of the high zinc sensor HIZR-1.bioRxiv : the preprint server for biology · 2026Article
- Osteoimmunology uncovered: How macrophages and biomaterials revolutionize bone healing.Materials today. Bio · 2026Review
- High-Throughput Toxicity Screening withEnvironmental science & technology · 2026Review
- Natural variation suggests candidate genes underlyingbioRxiv : the preprint server for biology · 2025Article
- Extreme QTL mapping enables the identification of novel zinc toxicity response loci in Drosophila melanogaster.Genetics · 2025Article
- CaeNDR, the Caenorhabditis Natural Diversity Resource.Nucleic acids research · 2024Article
- Interplay Between Polymorphic Short Tandem Repeats and Gene Expression Variation in Caenorhabditis elegans.Molecular biology and evolution · 2023Article
- Praziquantel inhibits Caenorhabditis elegans development and species-wide differences might be cct-8-dependent.PloS one · 2023Article
- Natural variation inGenome research · 2022Article
- Article
- Evaluating the power and limitations of genome-wide association studies in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2022Article
- The impact of species-wide gene expression variation on Caenorhabditis elegans complex traits.Nature communications · 2022Article
- Review
- From QTL to gene: C. elegans facilitates discoveries of the genetic mechanisms underlying natural variation.Trends in genetics : TIG · 2021Review
- Natural variation in Caenorhabditis elegans responses to the anthelmintic emodepside.International journal for parasitology. Drugs and drug resistance · 2021Article
- The Carcinogen Cadmium Activates Lysine 63 (K63)-Linked Ubiquitin-Dependent Signaling and Inhibits Selective Autophagy.Cancers · 2021Article
- Two novel loci underlie natural differences in Caenorhabditis elegans abamectin responses.PLoS pathogens · 2021Article
- The cadmium-responsive gene,microPublication biology · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Zinc is an essential trace element that acts as a co-factor for many enzymes and transcription factors required for cellular growth and development. Altering intracellular zinc levels can produce dramatic effects ranging from cell proliferation to cell death. To avoid such fates, cells have evolved mechanisms to handle both an excess and a deficiency of zinc. Zinc homeostasis is largely maintained via zinc transporters, permeable channels, and other zinc-binding proteins. Variation in these proteins might affect their ability to interact with zinc, leading to either increased sensitivity or resistance to natural zinc fluctuations in the environment. We can leverage the power of the roundworm nematode Caenorhabditis elegans as a tractable metazoan model for quantitative genetics to identify genes that could underlie variation in responses to zinc. We found that the laboratory-adapted strain (N2) is resistant and a natural isolate from Hawaii (CB4856) is sensitive to micromolar amounts of exogenous zinc supplementation. Using a panel of recombinant inbred lines, we identified two large-effect quantitative trait loci (QTL) on the left arm of chromosome III and the center of chromosome V that are associated with zinc responses. We validated and refined both QTL using near-isogenic lines (NILs) and identified a naturally occurring deletion in sqst-5, a sequestosome-related gene, that is associated with resistance to high exogenous zinc. We found that this deletion is relatively common across strains within the species and that variation in sqst-5 is associated with zinc resistance. Our results offer a possible mechanism for how organisms can respond to naturally high levels of zinc in the environment and how zinc homeostasis varies among individuals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.