Fig 1.
(A). The arsenic methylation capacity differs in different animal species. Urinary excretion of arsenic metabolites (InorgAs, inorganic arsenic; MMA, methylarsonic acid; and DMA, dimethylarsinic acid) in different species 2–4 days after ingestion of a single dose of arsenate. Derived from Vahter [13]. (B) Proposed pathway of biomethylation of arsenic in mammalian systems. Human arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyses methylation of trivalent arsenic (As(III)) to monomethylarsonate (MMA(V)) and dimethylarsinic acid (DMA(V)) with S-adenosylmethionine (SAM) as the methyl donor. (C) Schematic overview of primary structure of human AS3MT. The enzyme of 365 amino acid residues is organized in three domains [34]: A N-terminal domain (residues 1–70), a central domain (residues 71–263) with the methyltransferase domain (Methyltransf_31; residues 71–215), and a C-terminal domain (residues 264–315).
Fig 2.
Phylogenetic analysis of AS3MT proteins from animal, fungal, green and red algal, and other eukaryotic lineages, as well as archaeal and bacterial lineages demonstrates that AS3MT is present in a range of kingdoms.
The tree shown is the consensus tree derived by Bayesian inference using MrBayes, as described in Experimental procedures. MrBayes posterior probabilities are shown for branches with >0.5 MrBayes posterior probability support; branches with a value of 1 are shown by a filled circle. Bootstrap values of the same tree, derived by maximum likelihood using the program RAxML, are shown at key branches. AS3MT is phylogenetically split into one major group (I) divided into one subgroup of bacteria, SAR (stramenopiles, alveolata, rhizaria), and animals; and another major group (II) of bacteria, archaea, ascomycote and basidiomycote fungi, and Hydra magnipapillata. The species names and the database accession numbers are explained in S1 Table. Species that have two isoforms are shown with numbers 1 and 2 for the respective isoform.
Fig 3.
AS3MT shows very different phylogenetic relationships compared with other proteins in the same species.
Comparison of the phylogenetic trees based on AS3MT (A), the calcium pump SERCA2 (B), and the copper pump ATP7A (C) in the same species (indicated with numbers). Numbers refer to species as follows: Animals: 1, Homo sapiens; 2, Macaca mulatta; 3, Colobus angolensis palliatus; 4, Trichechus manatus latirostris; 5, Mus musculus; 6, Gallus gallus; 7, Chelonia mydas; 8, Danio rerio; 9, Astyanax mexicanus; 10, Callorhinchus milii; 11, Latimeria chalumnae; 12, Branchiostoma floridae; 13, Xenopus tropicalis; 14, Saccoglossus kowalevskii; 15, Capitella telata; 16, Crassostrea gigas; 17, Lottia gigantea; 18, Biomphalaria glabrata; 19, Lingula anatina; 20, Strongylocentrotus purpuratus; 21, Hydra magnipapillata; 22, Nematostella vectensis; 23, Amphimedon queenslandica; Fungi: 24, Aspergillus nidulans FGSC A4; 25, Penicillium expansum; 26, Neosartorya fischeri NRRL 181; 27, Talaromyces cellulolyticus; 28, Byssochlamys spectabilis No. 5; 29, Trichophyton tonsurans CBS 112818; 30, Exophiala aquamarina CBS 119918; 31, Coccidioides immitis RS; 36, Pseudogymnoascus pannorum VKM F-4514; 37, Westerdykella aurantiaca; 38, Metarhizium robertsii ARSEF 23; 32, Trichosporon oleaginosus; 33, Serendipita vermifera MAFF 305830; 34, Trichosporon asahii var. asahii CBS 8904; 35, Schizophyllum commune H4-8; 36, Pseudogymnoascus pannorum VKM F-4514; 37, Westerdykella aurantiaca; 38, Metarhizium robertsii ARSEF 23; 39, Rhizophagus irregularis; 40, Spizellomyces punctatus DAOM BR117; Green algae: 41, Chlamydomonas reinhardtii; 42, Volvox carteri f. nagariensis; 43, Chlorella variabilis; 44, Micromonas pusilla CCMP1545; 45, Ostreococcus tauri; 46, Bathycoccus prasinos; Charophyta: 47, Klebsormirdium flaccidum; Red algae: 48, Cyanidioschyzon merolae strain 10D; 49, Cyanidioschyzon sp. 5508; 50, Galdieria sulphuraria; Excavata: 51, Naegleria gruberi NEG-M; 52, Trichomonas vaginalis G3; Amoebozoa; 53, Acanthamoeba castellanii str. Neff; SAR: 54, Thalassiosira pseudonana CCMP1335; 55, Phaeodactylum tricornutum CCAP 1055/1; 56, Ectocarpus siliculosus; 57, Nannochloropsis gaditana CCMP526; 58, Emiliania huxleyi CCMP1516; 59, Stylonychia lemnae; 60, Oxytricha trifallax; 61, Plasmodiophora brassicae; Archaea: 62, Candidatus methanoplasma termitum; 63, Methanobacterium paludis; 64, Methanocella conradii; 65, Halapricum salinum; 66, Methanobacterium formicicum; 67, Haloterrigena limicola; Bacteria: 68, Pleomorphomonas koreensis; 69, Rhodopseudomonas palustris; 70, Rhodomicrobium udaipurense; 71, Pleomorphomonas oryzae; 72, Methyloceanibacter caenitepidi; 73, Halocynthiibacter namhaensis; 74, Erythrobacter gangjinensis; 75, Hyphomonas jannaschiana; 76, Ruegeria pomeroyi; 77, Celeribacter baekdonensis; 78, Parvibaculum lavamentivorans; 79, Leisingera caerulea; 80, Rubrivivax gelatinosus; 81, Thauera phenylacetica; 82, Nitrosospira briensis; 83, Paludibacterium yongneupense; 84, Ralstonia pickettii: 85, Nitrosomonas eutropha; 86, Caldimonas manganoxidans; 87, Azoarcus toluclasticus; 88, Rhodoferax ferrireducens; 89, Burkholderiales bacterium GJ-E10; 90, Gallionella capsiferriformans; 91, Candidatus Thiomargarita nelsonii; 92, Thioalkalivibrio thiocyanodenitrificans; 93, Methylomarinum vadi; 94, Methylomicrobium buryatense; 95, Alcanivorax pacificus; 96, Simiduia agarivorans; 97, Porticoccus hydrocarbonoclasticus; 98, Oleispira antarctica; 99, Zooshikella ganghwensis; 100, Paraglaciecola psychrophila; 101, Hahella ganghwensis; 102, Saccharophagus degradans; 103, Azotobacter chroococcum; 104, Endozoicomonas numazuensis; 105, Colwellia psychrerythraea; 106, Sedimenticola selenatireducens; 107, Pseudomonas alcaligenes; 108, Marinobacterium jannaschii; 109, Methylococcaceae bacterium 73a; 134, Nitrococcus mobilis Nb-231; 110, Desulfohalobium retbaense; 111, Desulfonatronovibrio magnus; 112, Desulfococcus oleovorans; 113, Geoalkalibacter ferrihydriticus; 114, Campylobacter curvus; 115, Mariprofundus ferrooxydans; 116, Tetrasphaera australiensis Ben110; 117, Streptomyces fradiae; 118, Streptomyces viridochromogenes DSM 40736; 119, Gordonibacter pamelaeae; 120, Sporolactobacillus vineae; 121, Desulfitobacterium hafniense; 122, Pelosinus fermentans JBW45; 123, Paenibacillus polymyxa; 124, Finegoldia magna; 125, Peptococcaceae bacterium CEB3; 126, Criblamydia sequanensis CRIB-18; 127, Sphaerobacter thermophilus DSM 20745; 128, Ktedonobacter racemifer DSM 44963; 129, Synechococcus sp. WH 5701; 130, Cyanobium gracile PCC 6307; 131, Nitrospira defluvii; 132, Gemmatimonas aurantiaca; 133, Bryobacter aggregatus. Details of taxonomy and database accession numbers are given in S1 Table. The trees with the highest log likelihood inferred from a maximum likelihood analysis by MEGA6, as described in the Methods section, are shown. Numbers at the nodes reflect the percentage of 1000 replicate bootstrap trees (only values of >70 and for nodes of important branches are presented). Red circles, animal isoforms; dark blue circles, fungal isoforms; green circles, green algal isoforms; dark red circles, red algal isoforms; light blue circles, SAR; dark grey circle, amoebozoa; light gray circle, excavata; yellow circles, bacteria; and pink circles, archaea.
Fig 4.
Suggested horizontal gene transfer events between bacteria and eukaryotes (dashed lines labelled I-V) for AS3MT throughout evolution.
Schematic tree of life originally based on Woese [90] and updated by Forterre [91].