ArticlePloS one2011
Gains, losses and changes of function after gene duplication: study of the metallothionein family.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 92 citations in OpenAlex.
- Identification of two metallothioneins in Agaricus crocodilinus reveals gene duplication and domain expansion, a pattern conserved across fungal species.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Methamphetamine Induces Metallothionein 1 Expression and an Inflammatory Phenotype in Primary Human HIV-Infected Macrophages.International journal of molecular sciences · 2025Article
- MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy.Scientific reports · 2025Article
- Genome-Wide Identification and Evolutionary Analysis ofAnimals : an open access journal from MDPI · 2025Article
- Identification of RP-54745, an IL-1 Inhibitor Displaying Anticancer Activities for KSHV-Related Primary Effusion Lymphoma.Journal of medical virology · 2025Article
- Oxidative pathways of apo, partially, and fully Zn(II)- and Cd(II)-metalated human metallothionein-3 are dominated by disulfide bond formation.The FEBS journal · 2025Article
- Biochemical Markers of Zinc Nutrition.Biological trace element research · 2024Review
- ESI-MS analysis of Cu(I) binding to apo and Zn7 human metallothionein 1A, 2, and 3 identifies the formation of a similar series of metallated species with no individual isoform optimization for Cu(I).Metallomics : integrated biometal science · 2024Article
- Single-Nucleotide Polymorphisms Associated with Mercury Levels and Neurological Symptoms: An Overview.Toxics · 2024Review
- Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis.Nutrients · 2024Review
- Metallothionein 3 promotes osteoclast differentiation and survival by regulating the intracellular ZnCell death discovery · 2023Article
- Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2023Article
- The genetic basis of adaptation to copper pollution inFrontiers in genetics · 2023Article
- The Difference in Zinc Concentrations Required for Induction among Metallothionein Isoforms Can Be Explained by the Different MTF1 Affinities to MREs in Its Promoter.International journal of molecular sciences · 2022Article
- Article
- Metallothionein 2A with Antioxidant and Antitumor Activity Is Upregulated by Caffeic Acid Phenethyl Ester in Human Bladder Carcinoma Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Regulation of zinc-dependent enzymes by metal carrier proteins.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
- Ionotropic receptors in the turnip moth Agrotis segetum respond to repellent medium-chain fatty acids.BMC biology · 2022Article
- Identification and characterization of eight metallothionein genes involved in heavy metal tolerance from the ectomycorrhizal fungus Laccaria bicolor.Environmental science and pollution research international · 2022Article
- Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metallothioneins (MT) are small proteins involved in heavy metal detoxification and protection against oxidative stress and cancer. The mammalian MT family originated through a series of duplication events which generated four major genes (MT1 to MT4). MT1 and MT2 encode for ubiquitous proteins, while MT3 and MT4 evolved to accomplish specific roles in brain and epithelium, respectively. Herein, phylogenetic, transcriptional and polymorphic analyses are carried out to expose gains, losses and diversification of functions that characterize the evolutionary history of the MT family. The phylogenetic analyses show that all four major genes originated through a single duplication event prior to the radiation of mammals. Further expansion of the MT1 gene has occurred in the primate lineage reaching in humans a total of 13 paralogs, five of which are pseudogenes. In humans, the reading frame of all five MT1 pseudogenes is reconstructed by sequence homology with a functional duplicate revealing that loss of invariant cysteines is the most frequent event accounting for pseudogeneisation. Expression analyses based on EST counts and RT-PCR experiments show that, as for MT1 and MT2, human MT3 is also ubiquitously expressed while MT4 transcripts are present in brain, testes, esophagus and mainly in thymus. Polymorphic variation reveals two deleterious mutations (Cys30Tyr and Arg31Trp) in MT4 with frequencies reaching about 30% in African and Asian populations suggesting the gene is inactive in some individuals and physiological compensation for its loss must arise from a functional equivalent. Altogether our findings provide novel data on the evolution and diversification of MT gene duplicates, a valuable resource for understanding the vast set of biological processes in which these proteins are involved.
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