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At least 19 recordsLinked to original sources
PubMed2026

Large-scale benchmarking of prokaryotic annotation tools across thousands of species.

BACKGROUND: Genome annotation is an important step in deriving functional meaning from prokaryotic sequencing data, yet systematic evaluations guiding tool selection are lacking. We present the first large-scale investigation of four prominent open-source annotation tools (Prokka, Bakta, EggNOG-mapper, and PGAP) across 156,033 diverse genomes. This includes Escherichia coli strains for baseline performance, thousands of archaea and bacteria genomes, as well as frameshifted and metagenome-assembled genomes. RESULTS: Bakta excels in annotating high-quality bacterial genomes, while PGAP was better for archaeal genomes and challenging bacterial assemblies, including metagenome-assembled, fragmented, or contaminated samples. For Gene Ontology annotation, PGAP consistently provides broader term coverage, whereas EggNOG-mapper offers more terms per feature. CONCLUSIONS: Our findings highlight tool-specific strengths crucial for selecting optimal solutions based on genome quality, taxonomy, and origin (e.g. MAGs). This study provides an evidence-based guide for users and informs future tool development.

Molecular Sequence Annotation↗
PubMed2025

CompareM2 is a genomes-to-report pipeline for comparing microbial genomes.

SUMMARY: Here, we present CompareM2, a genomes-to-report pipeline for comparative analysis of bacterial and archaeal genomes derived from isolates and metagenomic assemblies. CompareM2 is easy to install and operate, designed in such a way that the user can install the complete software in one step and launch all analyses on a set of microbial genomes (bacterial and archaeal) in a single action. The central results generated via the CompareM2 workflow are emphasized in a portable dynamic report document. AVAILABILITY AND IMPLEMENTATION: CompareM2 is a free software that is scalable to a range of project sizes, and welcomes modifications and pull requests from the community on its Git repository at https://github.com/cmkobel/comparem2.

Software↗
PubMed2026

An integrated culturomic and genomic database and analysis platform for methanogenic archaea.

Methanogenic archaea research is challenged by limited strain resources, fragmented genomic data, inconsistent genome quality, substantial uncultured lineages, and difficulties in laboratory culturing, hindering advances in biogas production, climate mitigation, and microbial ecology. These archaea play crucial roles in global carbon cycling and anaerobic environments, yet scattered data and unculturable strains limit systematic studies and applications. To address this, we created MethArDB (Methanogenic Archaeal Genome Database), a specialized database for methanogenic archaea, compiling 3919 genomes, 87 host-associated plasmids, and 42 phages, with standardized quality classifications (complete, scaffold, draft), protein sequences, and metadata on geography, habitats, metabolism, and inheritable elements. Integrated MethArCT (Methanogenic Archaeal Culturomics Toolkit) employs a dual-threshold orthologous/paralogous protein analysis to evaluate metabolic pathway completeness, predicting cultivation parameters and suggesting candidate cultivation strategies, including potential medium formulations and conditions, to support strain isolation. Overall, MethArDB and MethArCT form an integrated platform combining genomics and culturomics to facilitate methanogenic archaea research. Database URL:  http://methardb.cn.

Genome, Archaeal↗
PubMed2026

Novel Insights into Metagenomic-Assembled Genomes from Layer Chicken Housing Environment.

Culture-independent techniques are playing a major role in exploring unique and novel microbial communities from complex ecosystems, leading to an outstanding impact on our basic understanding of the tree of life. Microbial communities are not extensively studied in layer chicken housing environments, particularly from the point of view of taxa carrying antimicrobial resistance genes, virulence genes and their functional potential. This study aimed to extract metagenomic-assembled genomes (MAGs) from the Illumina short-reads shotgun metagenomics sequenced data that originated from an Alberta poultry barn environment and then to study host tracking of antimicrobial resistance genes (ARGs) and the roles of genes involved in functions related to ammonia production, short-chain fatty acid (SCFA)-related pathways, sulfur metabolism, methane emission, stress and disinfectant-related pathways. A total of 251 high-quality MAGs were extracted, including 249 bacterial and two archaeal genomes from sequencing data of 30 metagenomic sequencing samples comprising 15 air and 15 manure samples collected from 15-layer farms. Interestingly 22 bacterial MAGs were not classified to species levels using GTDB-based classification. ARGs were mainly harbored by the genera Staphylococcus, Alistepes, Romboutsia, and Enterococcus. Bacteroides is a main taxon carrying ARGs in air samples. Ammonia production-related genes were mainly tracked in Staphylococcus, Ruminococcus and Corynebacterium genera. The assimilatory sulfate reduction genes responsible for sulfur metabolism and hydrogenase-related genes responsible for hydrogen cycling were traced from Staphylococcus originated from both air and manure. The current study provides characterizations of MAGs from a poultry housing environment by linking microbial taxa with virulence, resistance, and metabolic functions. The findings emphasize the role of microbiota in shaping gas emissions and AMR, with implications for poultry health and worker's safety and the ultimate aim of sustainable poultry production.

Animals↗
PubMed2026

Genome-resolved assessment of archaeal diversity in full-scale anaerobic digesters reveals variability in mcrA primer coverage.

AIMS: Methanogenic archaea are key players in anaerobic digestion, driving methane production in biogas reactors. This study aimed to assess the diversity of methanogenic archaea in full-scale anaerobic digesters using genome-resolved metagenomics and to systematically evaluate the taxonomic coverage of commonly used mcrA-targeted qPCR primer sets against this genomic framework. METHODS AND RESULTS: Methanogenic diversity was assessed using 113 dereplicated archaeal metagenome-assembled genomes (MAGs) recovered from 109 full-scale anaerobic digesters treating diverse substrates. Genome-resolved analyses revealed a diverse archaeal community spanning multiple phyla, dominated by Halobacteriota and Methanobacteriota, with additional representatives from Methanobacteriota_B, Thermoplasmatota, and Thermoproteota. The presence of the mcrA gene was identified in a subset 55 MAGs, which were subsequently used as the genomic framework to evaluate six commonly used mcrA qPCR primer sets in silico. This subset clustered into nine phylogenetic groups and formed the basis for the primer coverage analysis. The evaluation revealed marked differences in taxonomic coverage among primer sets. Most primers preferentially detected Methanobacteriales and Methanosarcinales, while underrepresenting or excluding other methanogenic lineages, including H₂-dependent methylotrophic Methanomassiliicoccaceae. CONCLUSIONS: Commonly used mcrA primer sets differ substantially in their ability to capture methanogenic diversity, with some showing broad representation of reactor-associated methanogens and others exhibiting strong lineage-specific biases. Genome-resolved metagenomics provides an effective framework for benchmarking primer performance and supports the selection and improvement of molecular tools for more accurate monitoring of anaerobic digestion systems.

Archaea↗
PubMed2026

Phosphate backbone epitranscriptomics: Discovery of natural RNA phosphorothioates and their writer machinery.

Over 150 modifications expand the RNA alphabet, yet all known natural modifications occur on nucleobases or ribose sugars, with none identified on the phosphate backbone. In contrast, phosphorothioates (PSs), in which a non-bridging phosphate oxygen is replaced with sulfur, are central to RNA therapeutics but have never been reliably detected in natural RNAs. Here, we develop sequencing- and mass spectrometry-based approaches to quantitatively map RNA PSs at single-nucleotide resolution. Across diverse archaeal species, we identify stereospecific PS modifications at rRNA and tRNA hotspots, which are dynamically regulated by sulfur availability and temperature. We uncover a diverse enzyme family that selectively modifies tRNA/rRNA substrates and whose evolutionary presence/absence matches the distribution of PSs. Enzyme loss causes inviability or temperature sensitivity, and functional analyses reveal that tRNA PSs enhance tRNA stability. These findings establish the first natural RNA phosphate-backbone modification and its enzymatic machinery, providing a foundation for mechanistic and functional exploration.

RNA modifications↗
PubMed2026

Convergent evolution of intestinal lineages in the phylum Methanobacteriota.

BACKGROUND: Representatives of the phylum Methanobacteriota occur in various anoxic environments, but only members of the genera Methanosphaera and Methanobrevibacter exclusively colonize the digestive tract of animals. Recent phylogenomic analyses revealed that the genus Methanobrevibacter, which harbors the majority of the intestinal species, is severely underclassified and represents a family-level taxon, "Methanobrevibacteraceae", that evolved entirely in the digestive tract of animals. RESULTS: Comparative genome analysis of 158 species of Methanobacteriota, including uncultured representatives in the Genome Taxonomy Database (GTDB), demonstrated that the intestinal lineages are clearly separated from the remaining members of the phylum. They differ from the non-intestinal lineages in genome size, GC content, coding density, an increased number of pseudogenes and adhesin-like proteins, and show numerous adaptations to the copiotrophic gut environment. A decreased biosynthetic potential led to a dependence on other community members and limits the dispersal of intestinal species into other habitats, which is reflected in coevolutionary patterns with their major host groups among arthropods, ungulates, and primates. Certain lineages even engaged in symbiotic associations with intestinal protists, presumably benefiting from the H2 produced by the hydrogenosomes of their anaerobic hosts. CONCLUSIONS: Our results reveal that the transition of free-living Methanobacteriota to a host-associated lifestyle involves the same genomic changes that were previously recognized in gut bacteria and bacterial endosymbionts of protists, reflecting resemblances between the two prokaryotic domains that are caused by evolutionary convergence in similar environments.

Animals↗
PubMed2026

Unraveling the diversity, function, and virus-host interactions of archaeal proviruses.

Archaea, the third domain of life, play critical roles in global biogeochemical cycles. However, archaeal proviruses integrated into host genomes remain largely unexplored. To bridge this gap, we conducted a large-scale mining of genomes spanning all presently known 21 archaeal phyla for their proviruses. We identified 770 archaeal proviruses across 12 archaeal phyla and 84 families, which clustered into 655 viral operational taxonomic units (vOTUs). Among these, 86.1% of the vOTUs were novel at the species level, and 69.3% could not be classified at the family level, substantially expanding the known diversity of archaeal viruses. Additionally, phylogenomic analysis supported the proposal of 16 putative novel viral families, further extending the current taxonomy landscape of archaeal viruses. Notably, 21.8% of the identified proviruses were predicted to adopt a lytic lifestyle, suggesting that these proviruses may retain the capacity to enter the lytic cycle under appropriate conditions. Host prediction indicated only 14 out of the 655 vOTUs might have potential across-lineage infection abilities. We detected 63 anti-defense genes encoded by 61 provirus genomes, such as anti-CRISPR and anti-RM, suggesting an ongoing evolutionary arms race between hosts and proviruses. However, only 10 auxiliary metabolic genes (AMGs) were identified, suggesting a limited impact of proviruses in the modulation of host metabolism through AMGs. This study establishes a systematic global genomic atlas of archaeal proviruses, advancing our understanding of their distribution and diversity while providing a foundation for future research into how proviruses regulate archaeal metabolism and ecosystem functioning.

anti-defense system↗
PubMed2026

A genomic catalog of Earth's bacterial and archaeal symbionts.

Microbial symbiosis drives the functional and phylogenomic diversification of life on Earth yet remains underexplored because of culturing challenges. This study used machine learning (ML) to predict symbiotic lifestyles in more than a hundred thousand microbial genomes from diverse environmental metagenome samples and reference genomes. Predictions were performed using symclatron, an ML framework developed to identify genomic signatures of symbionts. Predictions were deposited in a catalog we established called Symbiont Genomes (SymGs). The results indicate that 15-23% of uncultivated microorganisms likely engage in symbiotic relationships with other organisms, categorized as host-associated or obligate intracellular lifestyles, and are present in half of all known bacterial and archaeal phyla. We also identify genomic signatures of symbiotic lifestyles, including the loss of certain metabolic functions and the differential presence of metabolic modules that may enable host-dependent living. The symclatron software and the SymGs catalog represent valuable resources for studying symbioses, potentially facilitating future mechanistic investigations and engineering of host-microorganism associations.

Journal Article↗
PubMed2026

Mechanosensitive channels dominate the minimal ion channel repertoire in prokaryotes.

The eukaryotic genomes encode hundreds of proteins that function as ion channels and transporters. Essential for sustaining life, these proteins mediate the movement of inorganic ions (e.g., K+, Na+, Cl-, and Ca2+) across the plasma membrane according to their electrochemical gradients. In multicellular organisms, a diverse array of ion channels contributes to the maintenance of the resting membrane potential, the regulation of pH, osmolarity, and cell volume, and the control of secretion, electrical excitability, and synaptic activity, among many other fundamental physiological processes. Although independent evolutionary origins have been proposed for several ion channel families, their relative hierarchical importance for cellular viability remains poorly understood. To advance our knowledge of ion channel evolutionary history, we focused on determining the minimal combination of permeabilities that allows cellular viability. To this end, we conducted a survey of representative prokaryotes with small genomes across bacterial and archaeal phyla. By focusing on the smallest genomes, our approach enabled the identification of five ion channel architectures shared among prokaryotes. Among these, non-selective mechanosensitive channels (MscS and MscL) are the most abundant, followed by potassium channels, CLC-type channels and proton channels of the MotA/TolQ/ExbB family. The conservation of the mechanosensitive protein architecture across archaeal and bacterial membranes suggests that the capacity to monitor physical membrane integrity predates the requirements for electrical communication.

Journal Article↗
PubMed2025

PICRUSt2-SC: an update to the reference database used for functional prediction within PICRUSt2.

SUMMARY: PICRUSt2 is a bioinformatic tool that predicts microbial functions in amplicon sequencing data using a database of annotated reference genomes. We have constructed an updated database for PICRUSt2 that has substantially increased the number of bacterial (19,493 to 26,868) and archaeal (406 to 1,002) genomes as well as the number of functional annotations present. The previous PICRUSt2 database relied on many timely and computationally intensive manual processes that made it difficult to update. We constructed a new streamlined process to allow regular upgrades to the PICRUSt2 database on an ongoing basis, and used this process to create a new database, PICRUSt2-SC (Sugar-Coated). Additionally, we have shown that this updated database contains genomes that more closely match study sequences from a range of different environments. The genomes contained in the database therefore better represent these environments and this leads to an improvement in the predicted functional annotations obtained from PICRUSt2. AVAILABILITY AND IMPLEMENTATION: PICRUSt2 source code is freely available at https://github.com/picrust/picrust2 and at https://anaconda.org/bioconda/picrust2. The latest version of PICRUSt2 at the time of writing is also archived: https://doi.org/10.5281/zenodo.15119781. The PICRUSt2-SC database comes pre-installed with PICRUSt2 from version 2.6.0 onwards. Step-by-step instructions for making the updated database are at https://github.com/picrust/picrust2/wiki/Updating-the-PICRUSt2-database. All code used for the analyses and figures in this manuscript is at https://github.com/R-Wright-1/PICRUSt2-SC_application_note and https://doi.org/10.5281/zenodo.15119770.

Software↗
PubMed2025

De novo discovery of conserved gene clusters in microbial genomes with Spacedust.

Metagenomics has revolutionized environmental and human-associated microbiome studies. However, the limited fraction of proteins with known biological processes and molecular functions presents a major bottleneck. In prokaryotes and viruses, evolution favors keeping genes participating in the same biological processes colocalized as conserved gene clusters. Conversely, conservation of gene neighborhood indicates functional association. Here we present Spacedust, a tool for systematic, de novo discovery of conserved gene clusters. To find homologous protein matches, Spacedust uses fast and sensitive structure comparison with Foldseek. Partially conserved clusters are detected using novel clustering and order conservation P values. We demonstrate Spacedust's sensitivity with an all-versus-all analysis of 1,308 bacterial genomes, identifying 72,843 conserved gene clusters containing 58% of the 4.2 million genes. It recovered 95% of antiviral defense system clusters annotated by the specialized tool PADLOC. Spacedust's high sensitivity and speed will facilitate the annotation of large numbers of sequenced bacterial, archaeal and viral genomes.

Metagenomics↗
PubMed2024

Discovery and characterization of complete genomes of 38 head-tailed proviruses in four predominant phyla of archaea.

Archaea play a significant role in natural ecosystems and the human body. Archaeal viruses exert a considerable influence on the structure and composition of archaeal communities and their associated ecological environments. The present study revealed the complete genomes of 38 archaeal head-tailed proviruses through comprehensive data mining. The hosts of these proviruses were identified as belonging to the following four dominant phyla: Halobacteriota, Thermoplasmatota, Thermoproteota, and Nanoarchaeota. In addition to the 14 proviruses of halophilic archaea related to the Graaviviridae family, the remaining proviruses exhibited limited genetic similarities to known (pro)viruses, suggesting the existence of 14 potential novel families. Of the 38 archaeal proviruses, 30 have the potential to lyse host cells. Eleven proviruses contain genes linked to antiviral defense mechanisms, including those involved in restriction modification (RM), clustered regularly interspaced short palindromic repeat (CRISPR)-associated (CRISPR-Cas) nucleases, defense island system associated with restriction-modification (DISARM), and DNA degradation (Dnd). Moreover, auxiliary metabolic genes were identified in the proviruses of Bathyarchaeia and Halobacteriota archaea, including those involved in carbohydrate and amino acid metabolism. Our findings indicate the diversity of archaeal viruses, their interactions with archaeal hosts, and their roles in the adaptation of the host.IMPORTANCEThe field of archaeal virology has seen a rapid expansion through the use of metagenomics, yet the diversity of these viruses remains largely uncharted. In this study, the complete genomes of 38 novel archaeal proviruses were identified for the following four dominant phyla: Halobacteriota, Thermoplasmatota, Thermoproteota, and Nanoarchaeota. Two families and six genera of Archaea were the first to be identified as hosts for viruses. The proviruses were found to contain diverse genes that were involved in distinct adaptation strategies of viruses to hosts. Our findings contribute to the expansion of the lineages of archaeal viruses and highlight their intricate interactions and essential roles in enabling host survival and adaptation to diverse environmental conditions.

Archaea↗
PubMed2025

Microbial genomic database of the Yangtze River, the third-longest river on Earth.

Microbes play an important role in mediating the nutrient cycling in the river ecosystem as a hotspot for biogeochemical processes. Due to scattered sampling efforts, however, there is a lack of a systematic study of the diversity of prokaryotic genomes in the Yangtze River, the third longest river on Earth. Here, we collected 602 metagenomic datasets of water, sediment and riparian soil samples spanning the Upper, Middle, and Lower basins of the Yangtze River over a 6,300 km continuum. We reconstructed 8,110 qualified genomes represented by 927 species-level genomes at the 95% ANI threshold, spanning 31 bacterial and five archaeal phyla. We further showed that more than half of these species (61.3% ~ 82.4%) were novel according to the genomic comparison against the curated databases, greatly expanding the known diversity of river prokaryotes. This dataset depicts an overview of microbial genomic diversity in the Yangtze River and provides a resource for in-depth investigation of metabolic potential, ecology, and evolution of riverine microbiomes.

Rivers↗
PubMed2026

The halophilic archaeon Halogranum roseipondis sp. nov. is susceptible to a virus carrying an exceptionally high number of viral tRNA genes.

UNLABELLED: Archaea constitute a diverse group of organisms, many of which inhabit extreme environments, such as haloarchaea that dominate hypersaline ecosystems, like solar salterns. Sampling of solar salterns and other hypersaline environments has resulted in numerous haloarchaeal isolates, including 3 classified and 27 uncharacterized Halogranum species. However, no complete genome has so far been reported for any member of this genus. Here, we present the first comprehensive study of Halogranum sp. SS5-1 isolated from a solar saltern in Samut Sakhon, Thailand. Hgn. SS5-1 is a pleomorphic, aerobic heterotroph that thrives in high salinity and moderate temperature and is capable of hydrolyzing starch. Its genome consists of a 3.6 Mbp chromosome and seven additional plasmids. Based on our phylogenetic analyses, which establish Hgn. SS5-1 as a distinct species, we propose that it will be classified as the novel species Halogranum roseipondis sp. nov. SS5-1T. Additionally, we report that Hgn. roseipondis sp. nov. SS5-1T is infected by Hagravirus capitaneum (HGTV-1), the only virus known to infect a Halogranum host. HGTV-1 exhibits a unique head-tailed morphology and encodes the largest archaeal virus double-stranded DNA genome known to date, including 34 tRNA-encoding genes. Codon usage analysis of the viral genome suggests partial alignment with host preferences, yet the abundance of viral tRNA genes hints at broader roles, potentially including roles in translation and host regulation. This study establishes Hgn. roseipondis and HGTV-1 as a novel virus-host system, opening avenues to explore infection dynamics and the roles of virus-encoded tRNA in archaea. IMPORTANCE: Archaea that thrive in high-salinity environments are key players in geochemical cycles and important contributors to ecosystem productivity. Despite their ecological significance and importance for the development of novel methodologies in synthetic biology, haloarchaea remain poorly studied. Further exploration of haloarchaea is required to obtain valuable information on the evolution of cellular complexity and the molecular mechanisms that allow cells to thrive in harsh environmental conditions. Here, we present the characterization of a novel archaeon, Halogranum roseipondis sp. SS5-1T, alongside the infection cycle of its associated virus, Hagravirus capitaneum. This tailed myovirus carries an extraordinary set of 34 viral tRNA genes, a feature that opens intriguing questions about virus-host interactions and translational control. Our findings lay the groundwork for future investigations into the expression and function of viral tRNAs in an archaeal model system, thereby opening a new frontier for studying archaeal translation and virus-driven modulation of host cellular processes.

Halobacteriaceae↗
PubMed2026

Taxonomic revision of the genus Methanobrevibacter, description of Methanomonile shimae gen. nov. sp. nov., and proposal of Methanobrevibacteraceae fam. nov.

Recent phylogenomic analyses revealed that the genus Methanobrevibacter, which consists almost exclusively of representatives from the intestinal tract of animals, is severely underclassified. Based on the large relative evolutionary divergence between individual subclades, members of the genus Methanobrevibacter have been reclassified into eight novel genera as new combinations proposed under the rules of the Code of Nomenclature of Prokaryotes Described from Sequence Data. Here, we validly publish the new names for all taxa with type strains also under the rules of the International Code of Nomenclature of Prokaryotes. This includes members of the genera Methanacia, Methanobaculum, Methanobinarius, Methanocatella and Methanoflexus. Moreover, we propose to place Methanobrevibacter acididurans, whose genome was only recently sequenced, in the new genus Methanobotrus and describe a new isolate from the gut of a cockroach as Methanomonile shimae gen. nov. sp. nov. Based on the large evolutionary distance from the remaining members of Methanobacteriaceae, we propose to reclassify all genera within the radiation of Methanobrevibacter sensu lato into their own family, Methanobrevibacteraceae fam. nov. In addition, we reclassify Methanothermobacter tenebrarum as Methanothermobaculum tenebrarum gen. nov. comb. nov. into a new family, Methanothermobaculaceae (Methanobacteriales) and provide emended descriptions for the phylum Methanobacteriota and the classes Methanobacteria and Methanococci.

Phylogeny↗
PubMed2024

Regulation of DNA Topology in Archaea: State of the Art and Perspectives.

DNA topology is a direct consequence of the double helical nature of DNA and is defined by how the two complementary DNA strands are intertwined. Virtually every reaction involving DNA is influenced by DNA topology or has topological effects. It is therefore of fundamental importance to understand how this phenomenon is controlled in living cells. DNA topoisomerases are the key actors dedicated to the regulation of DNA topology in cells from all domains of life. While significant progress has been made in the last two decades in understanding how these enzymes operate in vivo in Bacteria and Eukaryotes, studies in Archaea have been lagging behind. This review article aims to summarize what is currently known about DNA topology regulation by DNA topoisomerases in main archaeal model organisms. These model archaea exhibit markedly different lifestyles, genome organization and topoisomerase content, thus highlighting the diversity and the complexity of DNA topology regulation mechanisms and their evolution in this domain of life. The recent development of functional genomic assays supported by next-generation sequencing now allows to delve deeper into this timely and exciting, yet still understudied topic.

Archaea↗
PubMed2024

The Lrs14 family of DNA-binding proteins as nucleoid-associated proteins in the Crenarchaeal order Sulfolobales.

Organization of archaeal chromatin combines bacterial, eukaryotic, and unique characteristics. Many archaeal lineages harbor a wide diversity of small and highly expressed nucleoid-associated proteins, which are involved in DNA structuring. In Sulfolobales, representing model organisms within the Crenarchaeota, Sul7d, Cren7, Sul10a, and Sul12a are well-characterized nucleoid-associated proteins. Here, we combine evidence that the Lrs14 family of DNA binders is part of the repertoire of nucleoid-associated proteins in Sulfolobales. Lrs14-encoding genes are widespread within genomes of different members of the Sulfolobales, typically encoded as four to nine homologs per genome. The Lrs14 proteins harbor a winged helix-turn-helix DNA-binding domain and are typified by a coiled-coil dimerization. They are characterized by distinct sequence- and structure-based features, including redox-sensitive motifs and residues targeted for posttranslational modification, allowing a further classification of the family into five conserved clusters. Lrs14-like proteins have unique DNA-organizing properties. By binding to the DNA nonsequence specifically and in a highly cooperative manner, with a slight preference for AT-rich promoter regions, they introduce DNA kinks and are able to affect transcription of adjacent transcription units either positively or negatively. Genes encoding Lrs14-type proteins display considerable differential expression themselves in response to various stress conditions, with certain homologs being specific to a particular stressor. Taken together, we postulate that members of the Lrs14 family can be considered nucleoid-associated proteins in Sulfolobales, combining a DNA-structuring role with a global gene expression role in response to stress conditions.

DNA-Binding Proteins↗