Academic Journal
Metagenomic and phylogenetic analyses reveal gene-level selection constrained by bacterial phylogeny, surrounding oxalate metabolism in the gut microbiota
| Title: | Metagenomic and phylogenetic analyses reveal gene-level selection constrained by bacterial phylogeny, surrounding oxalate metabolism in the gut microbiota |
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| Authors: | Sromona D. Mukherjee, Mangesh Suryavanshi, John Knight, Dirk Lange, Aaron W. Miller |
| Source: | mSphere mSphere, Vol 10, Iss 6 (2025) |
| Publisher Information: | American Society for Microbiology, 2025. |
| Publication Year: | 2025 |
| Subject Terms: | oxalate, selfish gene, dietary toxins, gut microbiome, complex systems, gene radiation, Microbiology, QR1-502, Research Article |
| Description: | The gut microbiota is critical for neutralizing dietary toxins. Oxalate is a toxin commonly produced by plants to deter herbivory and is widely consumed in the human diet. Excess levels of systemic or urinary oxalate increase risk of multiple urologic and cardiometabolic diseases. The current study employed multiple amplicon-based and shotgun metagenomic methodologies, alongside comparative phylogenetic analyses, to interrogate evolutionary radiation surrounding microbial oxalate degradation within the human gut microbiome. In conservative genome-based estimates, over 30% of gut microbial species harbored at least one oxalate-handling gene, with the specific pathways used dependent on bacterial phylum. Co-occurrence analyses revealed interactions between specialist genes that can metabolize oxalate or its by-products, but not multi-functional genes that can act in more than one oxalate-related pathway. Specialization was rare at the genome level. Amplicon-based metagenomic sequencing of the oxalate-degrading gene, formyl-CoA transferase ( frc ), coupled with molecular clock phylogenetic analyses are indicative of rapid evolutionary divergence, constrained by phylum. This was corroborated by paired analyses of non-synonymous to synonymous substitutions (dN/dS ratios), which pointed toward neutral to positive selection. Sequence similarity network analyses of frc sequences suggest extensive horizontal gene transferring has occurred with the frc gene, which may have facilitated rapid divergence. The frc gene was primarily allocated to the Pseudomonodota phylum, particularly the Bradyrhizobium genus, which is a species capable of utilizing oxalate as a sole carbon and energy source. Collectively evidence provides strong support that, for oxalate metabolism, evolutionary selection occurs at the gene level, through horizontal gene transfer, rather than at the species level. IMPORTANCE A critical function of the gut microbiota is to neutralize dietary toxins, such as oxalate, which is highly prevalent in plant-based foods and is not degraded by host enzymes. However, little is known about the co-evolutionary patterns of plant toxins and the mammalian gut microbiota, which are expected to exhibit features of an evolutionary arms race. In the current work, we present molecular evidence that microbial genes for oxalate degradation are highly prevalent in humans, potentially driven by extensive horizontal gene transfer events. Phylogenetic analyses reveal that oxalate-degrading genes are under a positive selection pressure and have historically undergone rapid diversification events, which has led to diverse ecological strategies for handling oxalate by gut bacteria. Collectively, data shed light on potential evolutionary relationships between the diet and the gut microbiota that occur relatively independently of the mammalian host. |
| Document Type: | Article Other literature type |
| Language: | English |
| ISSN: | 2379-5042 |
| DOI: | 10.1128/msphere.00913-24 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/40358144 https://doaj.org/article/ae194d99ba934506a672ac3748429940 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....14444a72b879c7d9b7c5171bf3ced73c |
| Database: | OpenAIRE |
| ISSN: | 23795042 |
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| DOI: | 10.1128/msphere.00913-24 |