From gene to structure: Unraveling genomic dark matter in Ca. Accumulibacter DOI Creative Commons

Xiaojing Xie,

Xuhan Deng,

Liping Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 17, 2024

Abstract Candidatus Accumulibacter is a unique and pivotal genus of polyphosphate-accumulating organisms (PAOs) prevalent in wastewater treatment plants, plays mainstay roles the global phosphorus cycle. Whereas, efforts toward complete understanding their genetic metabolic characteristics are largely hindered by major limitations existing sequence-based annotation methods, leaving more than half protein-encoding genes unannotated. To address challenge, we developed comprehensive approach integrating pangenome analysis, gene-based protein structure function prediction, metatranscriptomic extending beyond constraints sequence-centric methodologies. The application to Ca . allowed establishment pan- proteome database, providing references for >200,000 proteins. Benchmarking on 28 genomes showed increases average coverage from 51% 83%. Genetic that had eluded exploration via conventional methods were unraveled. For instance, identification previously unknown phosphofructokinase gene suggests all Ca. encoded Embden-Meyerhof-Parnas pathway. A defined homolog phosphate-specific transport system accessory (PhoU) was actually an inorganic phosphate (Pit) protein, regulating Pit instead high-affinity (Pst), key emergence trait Accumulibacter. Additional lineage members found encoding denitrification pathways. This study offers readily usable transferable tool high-coverage reference databases diverse cultured uncultured bacteria, facilitating genomic dark matter bacterial domain. Synopsis integrated advanced unraveling applicable bacteria customerized database

Language: Английский

Viroid-like colonists of human microbiomes DOI Creative Commons
Ivan N. Zheludev, R. C. Edgar, María José López-Galiano

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 21, 2024

Here, we describe the "Obelisks," a previously unrecognised class of viroid-like elements that first identified in human gut metatranscriptomic data. "Obelisks" share several properties: (i) apparently circular RNA ~1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing entire genome, and (iii) open reading frames coding for novel protein superfamily, which call "Oblins". We find Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, are prevalent tested microbiome metatranscriptomes representatives detected ~7% analysed stool (29/440) ~50% oral (17/32). Obelisk compositions appear differ between anatomic sites capable persisting individuals, continued presence over >300 days observed one case. Large scale searches 29,959 (clustered at 90% nucleotide identity), examples from all seven continents diverse ecological niches. From this search, subset code Obelisk-specific variants hammerhead type-III self-cleaving ribozyme. Lastly, case bacterial species (Streptococcus sanguinis) defined laboratory strains harboured specific population. As such, comprise RNAs have colonised, gone unnoticed in, human, global microbiomes.

Language: Английский

Citations

19
Multiple Protein Structure Alignment at Scale with FoldMason DOI Creative Commons
Cameron L. M. Gilchrist, Milot Mirdita, Martin Steinegger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Abstract Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended our repository of available proteins structures, requiring fast and accurate MSTA methods. Here, we introduce FoldMason, a progressive method that leverages the alphabet from Foldseek, pairwise aligner, hundreds thousands protein exceeding quality state-of-the-art methods, while two orders magnitudes faster than other FoldMason computes confidence scores, offers interactive visualizations, provides speed accuracy large-scale analysis in era prediction. Using Flaviviridae glycoproteins, demonstrate how FoldMason’s MSTAs support phylogenetic below twilight zone. free open-source software: foldmason.foldseek.com webserver: search.foldseek.com/foldmason .

Language: Английский

Citations

16
Mapping glycoprotein structure reveals Flaviviridae evolutionary history DOI Creative Commons
Jonathon C.O. Mifsud, Spyros Lytras, Michael R. Oliver

et al.

Nature, Journal Year: 2024, Volume and Issue: 633(8030), P. 695 - 703

Published: Sept. 4, 2024

Language: Английский

Citations

16
Viroid-like colonists of human microbiomes DOI
Ivan N. Zheludev, R. C. Edgar, María José López-Galiano

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(23), P. 6521 - 6536.e18

Published: Oct. 31, 2024

Language: Английский

Citations

15
Discovery of a Thermostable Tagatose 4-Epimerase Powered by Structure- and Sequence-Based Protein Clustering DOI
Jiajun Chen, Dawei Ni, Yingying Zhu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(33), P. 18585 - 18593

Published: Aug. 12, 2024

d-Tagatose is a highly promising functional sweetener known for its various physiological functions. In this study, novel tagatose 4-epimerase from

Language: Английский

Citations

10
Complexity of the lichen symbiosis revealed by metagenome and transcriptome analysis of Xanthoria parietina DOI Creative Commons
Gulnara Tagirdzhanova, Klara Scharnagl, Neha Sahu

et al.

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Lichens are composite, symbiotic associations of fungi, algae, and bacteria that result in large, anatomically complex organisms adapted to many the world's most challenging environments. How such intricate, self-replicating lichen architectures develop from simple microbial components remains unknown because their recalcitrance experimental manipulation. Here, we report a metagenomic metatranscriptomic analysis Xanthoria parietina at different developmental stages. We identified 168 genomes symbionts lichen-associated microbes across sampled thalli, including representatives green three classes 14 bacterial phyla. By analyzing occurrence individual species thalli diverse environments, defined both substrate-specific core lichen. Metatranscriptomic principal fungal symbiont stages lichen, compared with axenically grown fungus, revealed differential gene expression profiles indicative lichen-specific transporter functions, specific cell signaling, transcriptional regulation, secondary metabolic capacity. Putative immunity-related proteins structurally conserved secreted resembling pathogen effectors were also identified, consistent role for immunity modulation morphogenesis.

Language: Английский

Citations

1
Cold seeps are potential hotspots of deep-sea nitrogen loss driven by microorganisms across 21 phyla DOI Creative Commons
Qiuyun Jiang, Lei Cao, Yingchun Han

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 14, 2025

Language: Английский

Citations

1
Reconstructing the last common ancestor of all eukaryotes DOI Creative Commons
Thomas A. Richards, Laura Eme, John M. Archibald

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(11), P. e3002917 - e3002917

Published: Nov. 25, 2024

Understanding the origin of eukaryotic cells is one most difficult problems in all biology. A key challenge relevant to question eukaryogenesis reconstructing gene repertoire last common ancestor (LECA). As data sets grow, sketching an accurate genomics-informed picture early cellular complexity requires provision analytical resources and a commitment sharing. Here, we summarise progress towards understanding biology LECA outline community approach inferring its wider repertoire. Once assembled, robust set will be useful tool for evaluating alternative hypotheses about eukaryotes evolution traits descendant lineages, with relevance diverse fields such as cell biology, microbial ecology, biotechnology, agriculture, medicine. In this Consensus View, put forth status quo agreed path forward reconstruct LECA's content.

Language: Английский

Citations

6
Tertiary-interaction characters enable fast, model-based structural phylogenetics beyond the twilight zone DOI Creative Commons
Caroline Puente-Lelièvre, Ashar J. Malik, Jordan Douglas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

Abstract Protein structure is more conserved than protein sequence, and therefore may be useful for phylogenetic inference beyond the “twilight zone” where sequence similarity highly decayed. Until recently, structural phylogenetics was constrained by lack of solved structures most proteins, reliance on distance methods which made it difficult to treat uncertainty statistically. AlphaFold has mostly overcome first problem making predictions readily available. We address second redeploying a alphabet recently developed Foldseek, highly-efficient deep homology search program. For each residue in structure, Foldseek identifies tertiary interaction closest-neighbor classifies into one twenty “3Di” states. test hypothesis that 3Dis can used as standard characters using dataset 53 from ferritin-like superfamily. performed 60 IQtree Maximum Likelihood runs compare structure-free, PDB, analyses, default versus custom model sets include 3DI-specific rate matrix. Analyses combine amino acids, 3Di characters, partitioning, models produce closest match distances tree Malik et al. (2020), avoiding long-branch attraction errors structure-free analyses. ultrafast bootstrapping confidence measures, take minutes instead weeks run desktop computers. These results suggest could soon routine practice phylogenetics, allowing re-exploration many fundamental problems.

Language: Английский

Citations

12
Structural characterization of macro domain–containing Thoeris antiphage defense systems DOI Creative Commons
Yun Shi, Veronika Masic, Tamim Mosaiab

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(26)

Published: June 26, 2024

Thoeris defense systems protect bacteria from infection by phages via abortive infection. In these systems, ThsB proteins serve as sensors of and generate signaling nucleotides that activate ThsA effectors. Silent information regulator SMF/DprA-LOG (SIR2-SLOG) containing effectors are activated cyclic ADP-ribose (ADPR) isomers 2'cADPR 3'cADPR, triggering nicotinamide adenine dinucleotide (NAD

Language: Английский

Citations

4