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Phylogenetically closely related bacteria can thrive in diverse environmental habitats due to adaptive evolution. Genomic changes resulting from adaptive evolution lead to variations in cellular function, metabolism, and secondary metabolite biosynthesis.
A minority of HIV-1-infected patients produce broadly neutralizing antibodies (bNAbs). Identification of viral and host correlates of bNAb production may help develop vaccines. We aimed to characterize the neutralizing response and viral and host-associated factors in Angola, which has one of the oldest, most dynamic, and most diverse HIV-1 epidemics in the world. Three hundred twenty-two HIV-1-infected adults from Angola were included in this retrospective study. Phylogenetic analysis of C2V3C3 env gene sequences was used for virus subtyping. Env-binding antibody reactivity was tested against polypeptides comprising the C2, V3, and C3 regions. Neutralizing-antibody responses were determined against a reference panel of tier 2 Env pseudoviruses in TZM-bl cells; neutralizing epitope specificities were predicted using ClustVis. All subtypes were found, along with untypeable strains and recombinant forms. Notably, 56% of the patients developed cross neutralizing, broadly neutralizing, or elite neutralizing responses. Broad and elite neutralization was associated with longer infection time, subtype C, lower CD4 + T cell counts, higher age, and higher titer of C2V3C3-specific antibodies relative to failure to develop bNAbs. Neutralizing antibodies targeted the V3-glycan supersite in most patients. V3 and C3 regions were significantly less variable in elite neutralizers than in weak neutralizers and nonneutralizers, suggesting an active role of V3C3-directed bNAbs in controlling HIV-1 replication and diversification. In conclusion, prolonged and low-level envelope V3C3 stimulation by highly diverse and ancestral HIV-1 isolates promotes the frequent elicitation of bNAbs. These results provide important clues for the development of an effective HIV-1 vaccine. Studies on neutralization by antibodies and their determinants in HIV-1-infected individuals have mostly been conducted in relatively recent epidemics caused by subtype B and C viruses. Results have suggested that elicitation of broadly neutralizing antibodies (bNAbs) is uncommon. The mechanisms underlying the elicitation of bNAbs are still largely unknown. We performed the first characterization of the plasma neutralizing response in a cohort of HIV-1-infected patients from Angola. Angola is characterized by an old and dynamic epidemic caused by highly diverse HIV-1 variants. Remarkably, more than half of the patients produced bNAbs, mostly targeting the V3-glycan supersite in HIV-1. This was associated with higher age, longer infection time, lower CD4 + T cell counts, subtype C infection, or higher titer of C2V3C3-specific antibodies relative to patients that did not develop bNAbs. These results may help develop the next generation of vaccine candidates for HIV-1.
The ability to accurately characterize wound pathogens is critical to informing clinical decisions for wound infections with complex treatment requirements. Acinetobacter baumannii is an impactful nosocomial pathogen in combat wounds and civilian hospital-acquired infections. An informed understanding of the phylogenetics and epidemiology of A. baumannii infections in military and civilian environments could guide approaches that improve antibiotic treatment regimens for both military and civilian patients. Whole-genome data for bacterial strains can be difficult to obtain due to challenges in culturing isolates from preserved military specimens. Metagenomic sequencing and assembly create opportunities for genomic analysis of pathogens directly from clinical specimens. The ability to perform comparative analyses between metagenome-derived genomes and culture-derived genomes would support a range of comparative bacterial genomic studies. Wound tissue biopsy and effluent samples from combat injuries were subjected to metagenomic sequencing and assembly. In total, 42 microbial metagenome-assembled genomes (MAGs) were obtained directly from metagenomic sequence data, 36 of which were designated “high” quality. Thirty of these genomes corresponded to Acinetobacter, with 29 mapping specifically to A. baumannii. Other observed genera included Bordetella, Citrobacter, Escherichia, and Pseudomonas. Single-copy and multi-copy orthologs were identified across Acinetobacter MAGs and publicly available isolate genomes derived from military and civilian sources. Both MAG and military isolate genomes were annotated with antimicrobial resistance data, and MAG genomes were statistically comparable to genomes obtained from isolates. Our results highlight the potential of de novo metagenome assembly for enabling high-resolution characterization directly from clinical specimens, thereby improving diagnostic precision, guiding antimicrobial stewardship, and enhancing understanding of pathogen evolution across diverse healthcare and battlefield environments.
Healing of traumatic wounds is complicated by infecting pathogens, with Pseudomonas aeruginosa and members of the Acinetobacter calcoaceticus-baumannii complex among the most common infectious agents. However, a full understanding of genotypic and phenotypic differences between circulating wound isolates is lacking. To address this, traumatic wounds were sampled at Emory University Hospital, and 24 isolates were characterized; we focused on P. aeruginosa and Acinetobacter due to their prevalence and tendency for antibiotic resistance. Even though these species are renowned for antibiotic resistance, only two of the tested isolates could be classified as multidrug resistant. Whole-genome sequencing and analysis revealed that isolates from different patients were genetically distinct; however, longitudinal isolates from the same patient were closely related and appeared to represent chronic colonization by the same strain. Phylogenetic analysis revealed that laboratory strains (PAO1 and AB5075) that were isolated decades previously and from different locations grouped closely to subsets of the recent wound isolates. Given the importance of biofilm formation in infection, the ability of the isolates to form biofilms was assessed; all isolates formed biofilms but showed temporal and magnitude differences. Analysis of a subset of isolates revealed that planktonic P. aeruginosa was resistant to human serum-mediated killing. While the same was true for the majority of Acinetobacter isolates, one showed planktonic sensitivity that was abrogated when grown in a biofilm. Taken together, these data reveal genotypic and phenotypic differences in circulating isolates of P. aeruginosa and A. baumannii.
Biological nitrogen fixation, the microbial reduction of atmospheric nitrogen to bioavailable ammonia, represents both a major limitation on biological productivity and a highly desirable engineering target for synthetic biology. However, the engineering of nitrogen fixation requires an integrated understanding of how the gene regulatory dynamics of host diazotrophs respond across sequence-function space of its central catalytic metalloenzyme, nitrogenase. Here, we interrogate this relationship by analyzing the transcriptome of Azotobacter vinelandii engineered with a phylogenetically inferred ancestral nitrogenase protein variant. The engineered strain exhibits reduced cellular nitrogenase activity but recovers wild-type growth rates following an extended lag period. We find that expression of genes within the immediate nitrogen fixation network is resilient to the introduced nitrogenase sequence-level perturbations. Rather the sustained physiological compatibility with the ancestral nitrogenase variant is accompanied by reduced expression of genes that support trace metal and electron resource allocation to nitrogenase. Our results spotlight gene expression changes in cellular processes adjacent to nitrogen fixation as productive engineering considerations to improve compatibility between remodeled nitrogenase proteins and engineered host diazotrophs.
Labyrinthulomycetes are a group of ubiquitous and diverse unicellular Stramenopiles and have long been known for their vital role in ocean carbon cycling. However, their ecological function from the perspective of organic matter degradation remains poorly understood. This study reports high-quality genomes of two newly isolated Labyrinthulomycetes strains, namely, Botryochytrium sp. strain S-28 and Oblongichytrium sp. strain S-429, and provides molecular analysis of their ecological functions using comparative genomics and a biochemical assay. Our results suggest that Labyrinthulomycetes may occupy multiple ecological niches in marine ecosystems because of the significant differences in gene function among different genera. Certain strains could degrade wheat bran independently by secreting cellulase. The key glycoside hydrolase families (GH1, GH5, and GH9) related to cellulase and the functional domains of carbohydrate-active enzymes (CAZymes) were more enriched in their genomes. This group can actively participate in marine biochemical cycles as decomposers. In contrast, other strains that could not produce cellulase may thrive as “leftover scavengers” and act as a source of nutrients to the higher-trophic-level plankton. In addition, our findings emphasize the dual roles of endoglucanase, acting as both exo- and endoglucanases, in the process of cellulose degradation. Using genomic, biochemical, and phylogenetic analyses, our study provides a broader insight into the nutritional patterns and ecological functions of Labyrinthulomycetes.
Fossil melanosomes are a major focus of paleobiological research because they can inform on the original coloration, phylogenetic affinities, and internal anatomy of ancient animals. Recent studies of vertebrate melanosomes revealed tissue-specific trends in melanosome-metal associations that can persist in fossils. In some fossil vertebrates, however, melanosomes from all body regions are enriched only in Cu, suggesting diagenetic overprinting of original chemistry. We tested this hypothesis using laboratory experiments on melanosomes from skin and liver of the African clawed frog Xenopus laevis. After maturation in Cu-rich media, the metal chemistry of melanosomes from these tissues converged toward a common composition, and original differences in Cu oxidation state were lost. Elevated Cu concentrations and a pervasive Cu(II) signal are likely indicators of diagenetically altered melanosomes. These results provide a robust experimental basis for interpretating the chemistry of fossil melanosomes.
Hot Lake is a small heliothermal and hypersaline lake in far north–central Washington State (USA) and is limnologically unusual because MgSO 4 rather than NaCl is the dominant salt. In late summer, the Hot Lake metalimnion becomes distinctly green from blooms of planktonic phototrophs. In a study undertaken over 60 years ago, these blooms were predicted to include green sulfur bacteria, but no cultures were obtained. We sampled Hot Lake and established enrichment cultures for phototrophic sulfur bacteria in MgSO 4 -rich sulfidic media. Most enrichments turned green or red within 2 weeks, and from green-colored enrichments, pure cultures of a lobed green sulfur bacterium (phylum Chlorobi) were isolated. Phylogenetic analyses showed the organism to be a species of the prosthecate green sulfur bacterium Prosthecochloris. Cultures of this Hot Lake phototroph were halophilic and tolerated high levels of sulfide and MgSO 4 . In addition, unlike all recognized species of Prosthecochloris, the Hot Lake isolates grew at temperatures up to 45°C, indicating an adaptation to the warm summer temperatures of the lake. Photoautotrophy by Hot Lake green sulfur bacteria may contribute dissolved organic matter to anoxic zones of the lake, and their diazotrophic capacity may provide a key source of bioavailable nitrogen, as well.
This software builds on PHAME developed at LANL to generate phylogenetic trees of bacterial whole genome sequences. Where PHAME uses whole genome alignments to generate informative sites to base tress on, PHAME-OuS annotates bacterial genes, identifies orthologous sequences, aligns related proteins, uses those alignments to inform transcript alignments, then builds trees with several methods. The first is a conventional gene concatenation and ML tree estemation method. The second attempts to reconcile gene tree with a unified species tree using quartets (ASTRAL). Both methods allow filtering of gene lists on number of species represented, length, and gappiness in order to tune noise-to-signal for tree estimation
Speciose populations of small xanthoid crabs on offshore banks and reefs of the northern Gulf of Mexico include a new species that is not assignable to presently named genera. Morphological diagnoses of the new genus and species are underpinned by previously published gene sequence analyses, originally misattributed to another species but now known to apply to this taxon. Herein named Guinope tiara n. gen., n. sp., the species shows molecular phylogenetic affinities with the family Linnaeoxanthidae Stevcic, 2005, an ally of panopeid and pseudorhombilid crabs. Specimens from Occulina banks off the Florida Atlantic coast, previously regarded to represent Garthiope barbadensis (Rathbun, 1921), are not that species but instead morphologically assignable to Guinope n. gen. Whether they represent variants of Guinope tiara n. gen, n. sp. or a second species of the genus awaits the collection of fresh materials for DNA analyses.
Several specimens of a small panopeid crab from coastal waters of the western Gulf of Mexico were long suspected to represent an undescribed species and are herein designated as representatives of a new genus. While the originally collected specimens from over four decades ago were not of gene-sequence quality, later collections from the same locality produced materials that yielded sequence data for inclusion in molecular phylogenetic studies. Building on results of those analyses, the present taxonomic description draws upon morphology to support the description of a unique species in which especially the male first gonopods differ from those of all other described panopeid genera. To date, the species remains known from only two western Gulf of Mexico sites, both of which are wave-washed intertidal rocky habitats where substrates are heavily burrowed by boring bivalves and sipunculans. While we cannot exclude the possibility that the species was introduced, recurrent collections show its populations to be at very least persistent, the species most likely being a long-overlooked among a confusing hard-substrate assemblage of small panopeid crabs.
A new species of axiid was discovered during sampling offshore deep banks on the middle continental shelf off Louisiana. Paraxiopsis kensleyi n. sp. appears to inhabit interstices and cavities of coralline algal rubble, rhodoliths, coral rubble, and other eroded calcareous substrates. Weakly separated from Eutrichocheles Wood-Mason, 1876 on the basis of morphology, present assignments of western Atlantic species to Paraxiopsis de Man, 1905 are regarded as provisional. The new species is described morphologically, and the coloration of freshly captured specimens is documented and compared to related species where possible. Coloration readily distinguishes mature specimens of the new species from Paraxiopsis spinipleura Kensley, 1996, with which it was initially confused. The diagnosis includes GenBank accession numbers for COI sequences to allow future molecular phylogenetic comparisons. Compared to regional species that share a similar dentation or spination on the submedian carina, the pleon of the new species is distinctive in the truncate ventral margin on pleura 2–4, as opposed to being broadly rounded or directed ventrally in an acutely triangular tip. The new species is the eighteenth species of Paraxiopsis worldwide and the ninth from western Atlantic waters, seven of which are now known to range into the Gulf of Mexico. An updated key to western Atlantic members of the genus is provided.
A new species of panopeid crab from shallow coastal waters of Belize is formally described and named based upon comparative study of three small specimens obtained in the course of a regional biodiversity survey of decapod crustaceans. The herein designated holotype of Hexapanopeus klausruetzleri n. sp. is a specimen previously included in a comparative molecular phylogenetic analysis that showed it to be closely related to, but genetically distinct from, the western Atlantic species Hexapanopeus angustifrons (Benedict & Rathbun, 1891). Hexapanopeus klausruetzleri n. sp. differs from this widely reported warm-temperate species in both its smoother carapace and pereopod surfaces and its generally more lobiform anterolateral teeth. The unique male first gonopod of the new species also strongly supports its morphological separation from all known congeners and other superficially similar western Atlantic panopeids with which it might be confused. To date, mature females have not been found, and the limited available collections are restricted to the vicinity of Carrie Bow Cay and nearby waters. Fourteen additional species of small panopeid and pseudorhombilid crabs, similar to Hexapanopeus klausruetzleri n. sp. in size and general habitus, were taken in the course of our studies in Belize. Most have not been previously reported from these waters, and several warrant further study to confirm their identifications.
A recent molecular phylogenetic analysis that focused on selected species of western Atlantic Paguristes Dana, 1851, Areopaguristes Rahayu & McLaughlin, 2010, and Pseudopaguristes McLaughlin, 2002 was somewhat inconclusive regarding relationships among those genera, but it revealed two new unrecognized species genetically related to members of the Paguristes tortugae complex. One of the new species is sister to A. hummi (Wass, 1955), which is readily separated from Wass’ taxon by significant differences in coloration. However, no definitive characters have been found for its identification on the basis of structural morphology. A second new species is genetically sister to P. tortugae Schmitt, 1933, even though it was regarded in earlier literature as no more than an ecomorphic variant expressing protective coloration related to habitat substrate color. In addition to its unique coloration, subtle distinctions are evident in structural morphology. Both species are formally named with accompanying morphological and color descriptions.
The colonization of land and the diversification of terrestrial plants is intimately linked to the evolutionary history of their symbiotic fungal partners. Extant representatives of these fungal lineages include mutualistic plant symbionts, the arbuscular mycorrhizal (AM) fungi in Glomeromycota and fine root endophytes in Endogonales (Mucoromycota), as well as fungi with saprotrophic, pathogenic and endophytic lifestyles. These fungal groups separate into three monophyletic lineages but their evolutionary relationships remain enigmatic confounding ancestral reconstructions. Their taxonomic ranks are currently fluid. In this study, we recognize these three monophyletic linages as phyla, and use a balanced taxon sampling and broad taxonomic representation for phylogenomic analysis that rejects a hard polytomy and resolves Glomeromycota as sister to a clade composed of Mucoromycota and Mortierellomycota. Low copy numbers of genes associated with plant cell wall degradation could not be assigned to the transition to a plant symbiotic lifestyle but appears to be an ancestral phylogenetic signal. Both plant symbiotic lineages, Glomeromycota and Endogonales, lack numerous thiamine metabolism genes but the lack of fatty acid synthesis genes is specific to AM fungi. Many genes previously thought to be missing specifically in Glomeromycota are either missing in all analyzed phyla, or in some cases, are actually present in some of the analyzed AM fungal lineages, e.g. the high affinity phosphorus transporter Pho89. Based on a broad taxon sampling of fungal genomes we present a well-supported phylogeny for AM fungi and their sister lineages. We show that among these lineages, two independent evolutionary transitions to mutualistic plant symbiosis happened in a genomic background profoundly different from that known from the emergence of ectomycorrhizal fungi in Dikarya. These results call for further reevaluation of genomic signatures associated with plant symbiosis.
Background Protein language models (PLMs) have revolutionized protein fitness prediction, yet their application to rapidly evolving viral pathogens is often confounded by extreme sequence homology. This homology leads to “data leakage” in standard random validation splits, yielding inflated performance metrics that fail to translate into real-world biosurveillance utility. Results We present Protein Representation Inference for Mutation Evaluation (PRIME), a framework that integrates domain-specific fine-tuning with a rigorous position-stratified validation protocol to evaluate viral threats. Using a dataset of 347,432 SARS-CoV-2 receptor binding domain (RBD) sequences, we demonstrate that while random training data split yields deceptive R 2 values (> 0.90), they fail to generalize to novel mutational sites. By benchmarking models up to 650 M parameters, we show that domain-specific fine-tuning of the ESM-C 600 M model with correctly stratified data provides an initial demonstration of predictive signal for binding affinity and expression at unseen mutational sites of binding affinity and expression on unseen sites (R 2 ~0.23), a significant advancement over base foundation models which exhibit no predictive power (R 2 <0). PRIME’s embedding-based clustering identified 3.03% of bat coronavirus sequences as candidates for further experimental prioritization based on their functional similarity to human-infective strains in embedding space, offering a perspective complementary to traditional phylogenetic methods. Conclusion PRIME establishes a new benchmark for the application of PLMs in pathogen surveillance. Our findings demonstrate that state-of-the-art models and fine-tuning, when paired with stratified validation, provide biologically meaningful insights into pathogen evolution and zoonotic risk.
Background: Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Results: Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. Conclusions: These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.