On the Origin and Evolution of Microbial Mercury Methylation
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Abstract
The origin of microbial mercury methylation has long been a mystery. Here, we employed genome-resolved phylogenetic analyses to decipher the evolution of the mercury-methylating gene, hgcAB, constrain the ancestral origin of the hgc operon, and explain the distribution of hgc in Bacteria and Archaea. We infer the extent to which vertical inheritance and horizontal gene transfer have influenced the evolution of mercury methylators and hypothesize that evolution of this trait bestowed the ability to produce an antimicrobial compound (MeHg+) on a potentially resource-limited early Earth. We speculate that, in response, the evolution of MeHg+-detoxifying alkylmercury lyase (encoded by merB) reduced a selective advantage for mercury methylators and resulted in widespread loss of hgc in Bacteria and Archaea.
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A few putative HGT events could be inferred from the larger clade of the HgcA tree e.g., Marinimicrobia-HgcA clustered with Euryarchaeota-HgcA in the archaeal cluster,
Was the inference made by position in the tree or analyzing the pairwise sequence identity similarity of the proteins from this Archaea/Marinimicrobia? I am curious because in McDaniel et al. 2020 mSystems we also found only a few potentially clear cases of HGT but did this through pairwise sequence analysis, for example for a case of Deltaproteobacteria/Acidobacteria/Verrucomicrobia/Actinobacteria in permafrost
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Figure 3.
Are these trees rooted with either cdh outgroups or fused hgcAB? I see the symbol for fused hgcAB but in Gionfriddo et al. 2020 fused sequences are usually used to root the tree for accurate topology inference
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Nevertheless, several hgcA+ genomes did not carry neighbouring hgcB genes, including all Nitrospina and a few Deltaproteobactiera and Firmicutes, potentially because of gene loss during evolution or incomplete transfer events (i.e., only hgcA genes were acquired during the HGT events).
I wanted to clarify something from the methods - were just the hgcAB proteins from uniprot pulled down or the entire genome sequences for these hgcAB+ representatives? If you did have the entire genome, did you check for the cases where hgcB was missing if hgcA fell close to the end of a contig or not? I think Peterson et al. 2020 ES&T had a couple cases that hgcA was at the end of a contig
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To investigate the evolutionary history of HgcA, we further enlarged the sample size by retrieving HgcA homologs in UniProt Reference Proteomes database v2022_03 at 75% cutoff (RP75). Two other datasets, including one containing 700 representative prokaryotic proteomes constructed by Moody et al. (2022) and another containing several novel hgc-carriers published by Lin et al. (2021), were retrieved and incorporated into the RP75 dataset. Totally 169 HgcA sequences were collected after removing redundancies
I might have missed something, but it appears that you have included hgcAB sequences that are either included in the PF03599 protein family or MAGs from Lin et al. Are the HgcA protein sequences from the large curation efforts from McDaniel et al. 2020, Capo et al. 2022, and Gionfriddo et al. 2020 for example integrated into this …
To investigate the evolutionary history of HgcA, we further enlarged the sample size by retrieving HgcA homologs in UniProt Reference Proteomes database v2022_03 at 75% cutoff (RP75). Two other datasets, including one containing 700 representative prokaryotic proteomes constructed by Moody et al. (2022) and another containing several novel hgc-carriers published by Lin et al. (2021), were retrieved and incorporated into the RP75 dataset. Totally 169 HgcA sequences were collected after removing redundancies
I might have missed something, but it appears that you have included hgcAB sequences that are either included in the PF03599 protein family or MAGs from Lin et al. Are the HgcA protein sequences from the large curation efforts from McDaniel et al. 2020, Capo et al. 2022, and Gionfriddo et al. 2020 for example integrated into this uniprot release? It would seem easier in this case to pull directly from the Capo et al. database since those are curated sequences and metadata to link back to, unless I'm missing how Uniprot accessions work with incorporating data from MAGs
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We mapped the presence/absence of merB and hgc genes onto the Tree of Life
If I interpreted the methods correctly, this tree only includes ribosomal proteins from genomes that either have hgcAB/merB or both of them. This isn't exactly overlaying hgcAB/merB presence/absence onto the "tree of life" because to accurately portray these relationships you would also want to include genomes that have neither or these operons. To do this accurately you would want to overlay the information you have here including genomes that are in Hug et al. 2016 for example
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Our study reveals an ancient origin for microbial mercury methylation, evolving from LUCA to radiate extensively throughout the tree of life both vertically, albeit with extensive loss, and to a lesser extent horizontally.
I think to make a statement like this you would need more extensive analyses quantitatively calculating gene transfer rates and using tree dating methods such as in https://journals.asm.org/doi/10.1128/mBio.00644-17
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We mapped the presence/absence of merB and hgc genes onto the Tree of Life
If I interpreted the methods correctly, this tree only includes ribosomal proteins from genomes that either have hgcAB/merB or both of them. This isn't exactly overlaying hgcAB/merB presence/absence onto the "tree of life" because to accurately portray these relationships you would also want to include genomes that have neither or these operons. To do this accurately you would want to overlay the information you have here including genomes that are in Hug et al. 2016 for example
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Our study reveals an ancient origin for microbial mercury methylation, evolving from LUCA to radiate extensively throughout the tree of life both vertically, albeit with extensive loss, and to a lesser extent horizontally.
I think to make a statement like this you would need more extensive analyses quantitatively calculating gene transfer rates and using tree dating methods such as in https://journals.asm.org/doi/10.1128/mBio.00644-17
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Figure 3.
Are these trees rooted with either cdh outgroups or fused hgcAB? I see the symbol for fused hgcAB but in Gionfriddo et al. 2020 fused sequences are usually used to root the tree for accurate topology inference
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Nevertheless, several hgcA+ genomes did not carry neighbouring hgcB genes, including all Nitrospina and a few Deltaproteobactiera and Firmicutes, potentially because of gene loss during evolution or incomplete transfer events (i.e., only hgcA genes were acquired during the HGT events).
I wanted to clarify something from the methods - were just the hgcAB proteins from uniprot pulled down or the entire genome sequences for these hgcAB+ representatives? If you did have the entire genome, did you check for the cases where hgcB was missing if hgcA fell close to the end of a contig or not? I think Peterson et al. 2020 ES&T had a couple cases that hgcA was at the end of a contig
-
A few putative HGT events could be inferred from the larger clade of the HgcA tree e.g., Marinimicrobia-HgcA clustered with Euryarchaeota-HgcA in the archaeal cluster,
Was the inference made by position in the tree or analyzing the pairwise sequence identity similarity of the proteins from this Archaea/Marinimicrobia? I am curious because in McDaniel et al. 2020 mSystems we also found only a few potentially clear cases of HGT but did this through pairwise sequence analysis, for example for a case of Deltaproteobacteria/Acidobacteria/Verrucomicrobia/Actinobacteria in permafrost
-
To investigate the evolutionary history of HgcA, we further enlarged the sample size by retrieving HgcA homologs in UniProt Reference Proteomes database v2022_03 at 75% cutoff (RP75). Two other datasets, including one containing 700 representative prokaryotic proteomes constructed by Moody et al. (2022) and another containing several novel hgc-carriers published by Lin et al. (2021), were retrieved and incorporated into the RP75 dataset. Totally 169 HgcA sequences were collected after removing redundancies
I might have missed something, but it appears that you have included hgcAB sequences that are either included in the PF03599 protein family or MAGs from Lin et al. Are the HgcA protein sequences from the large curation efforts from McDaniel et al. 2020, Capo et al. 2022, and Gionfriddo et al. 2020 for example integrated into this …
To investigate the evolutionary history of HgcA, we further enlarged the sample size by retrieving HgcA homologs in UniProt Reference Proteomes database v2022_03 at 75% cutoff (RP75). Two other datasets, including one containing 700 representative prokaryotic proteomes constructed by Moody et al. (2022) and another containing several novel hgc-carriers published by Lin et al. (2021), were retrieved and incorporated into the RP75 dataset. Totally 169 HgcA sequences were collected after removing redundancies
I might have missed something, but it appears that you have included hgcAB sequences that are either included in the PF03599 protein family or MAGs from Lin et al. Are the HgcA protein sequences from the large curation efforts from McDaniel et al. 2020, Capo et al. 2022, and Gionfriddo et al. 2020 for example integrated into this uniprot release? It would seem easier in this case to pull directly from the Capo et al. database since those are curated sequences and metadata to link back to, unless I'm missing how Uniprot accessions work with incorporating data from MAGs
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