PLoS Biology最新文献

The ecological impacts of biological invasions vary widely in type, scale, and severity, highlighting the need for consistent assessment tools. The Environmental Impact Classification for Alien Taxa (EICAT) provides a standardized framework for assessing their effects, but focuses mainly on population-level impacts. We introduce the Extended EICAT (EEICAT), which incorporates impacts across three ecological dimensions, from individuals to ecosystems, with an impact-based approach. EEICAT enables classification of 19 impact types at the invasion-event level, making it suitable for primary research, synthesis, and management. This framework aims to improve the detection, comparison, and communication of complex ecological impacts caused by biological invasions.

The genetic structure of bacterial species is most often interpreted in terms of demographic processes such as clonal descent, but can also reflect natural selection and hence give functional and ecological insight. Klebsiella pneumoniae (KP) disperses effectively around the world and has high recombination rates, which should result in the species having a well-mixed gene pool. Nevertheless, phylogenies based on diverse KP strains contain a "backbone." This structure reflects a component of variation where the first component in Principal Components Analysis (PCA), PC1, explains 16.8% of the total variation. We propose that the component reflects a "bacterial ecocline" generated by diversifying selection on a quantitative genetic trait. We simulated the evolution of a bacterial population with a polygenic quantitative trait, where strains with the most extreme trait values have a small advantage. These simulations can recapitulate our KP PCA results and other features of its genetic diversity. As well as providing an explanation for the phylogenetic backbone, our results provide insight into how species such as KP can speciate, via stronger selection on the trait or a reduction in gene flow. Our hypothesis that there is a bacterial ecocline in KP raises two questions, namely what the trait is underlying it and why is the trait under diversifying selection? The genes that are most strongly associated with PC1 provide some hints, with the top locus encoding Kpa fimbriae. Identification of the trait, if it exists, should facilitate insight into selection on quantitative genetic traits in natural bacterial populations, which have largely been unstudied in microbiology, except in the atypical context of antibiotic resistance.

Recessive lethal mutations are widespread across studied species, with estimates suggesting that each individual carries at least one. Numerous lethal alleles persist in wild populations at higher frequencies than expected given their extreme deleterious nature. Though these findings spurred historical debate whether classical balancing selection maintains some lethal alleles at elevated frequencies (versus mutation-selection balance acting alone), we propose the question remained unanswered, especially given that the genetic basis of most naturally occurring lethal effects is still unknown. Given current genome-wide point mutation rate estimates, mutation-selection balance alone cannot explain some of this lethal variation in nature. However, evolutionary biologists have historically studied genetic variation through a lens of single-nucleotide variants, when in fact the spectrum of mutational changes is far broader than point mutations alone, including indels, structural variants, short tandem repeats, and transposable element insertions. We uncover the genetic basis of lethality in nature and provide insight on the possible evolutionary forces allowing some to persist at higher frequencies. By locating hundreds of recessive lethal mutations in Drosophila melanogaster via complementation testing, fine-mapping, and sequencing a subset, we determine candidate lethal mutations in specific genes. We discover that many lethal disruptions are likely caused by transposable element insertions. The most common transposable elements in our data, Transib1 and Kuruka, are both estimated to have recently invaded D. melanogaster, each from a different Drosophila species (between 2013-2016 and 2017-2021, respectively). This finding demonstrates that the many lethal alleles studied in D. melanogaster in the last century had a distinct genetic basis. Hence, we propose a model that could explain lethal variation in natural populations of D. melanogaster: lethal mutation frequencies are driven by invasions of new transposable elements and as time passes after each invasion, those frequencies decline as D. melanogaster evolves suppression mechanisms, allowing for natural selection to more efficiently remove lethal insertions. Upon the invasion of a new TE, the cycle repeats. The ubiquity of lethal alleles in natural populations is a classic conundrum for evolutionary geneticists for over a century, and this study utilized modern tools and sequencing technology to provide novel insight into this age-old mystery.

Motor learning induces alterations in neural activity that can persist long after the effects of such learning have faded. These persistent neural alterations are thought to manifest behaviorally as "savings," or faster relearning, via access to a latent motor memory. How the human brain forms and retrieves these latent memories, and the specific neural systems involved, remains unresolved. Here, using human functional MRI and a two-day sensorimotor adaptation paradigm, we show that savings are associated with the reinstatement of a large-scale cortical manifold structure formed during initial learning. Notably, this neural reinstatement effect was not observed across sensorimotor systems but was localized to regions of the default mode network (DMN). Moreover, the specific dynamics of DMN activity were linked to inter-subject differences in patterns of learning and relearning across days. These results suggest that motor savings arises from the re-expression of DMN activity patterns associated with initial learning, establishing a key role for this network in motor memory formation and retrieval. This finding, paralleling reinstatement principles from other memory domains (episodic memory, fear conditioning) and anticipated by recent computational models of motor learning, suggests a common mechanism for the flexible recall and reuse of stored memories across diverse behavioral contexts.

The central circadian clock of the suprachiasmatic nucleus (SCN) consists of a network of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the precise role of GABAergic transmission in the SCN remains unclear. In this study, we investigated the GABAergic regulation from arginine vasopressin (AVP)-producing neurons in the SCN shell to vasoactive intestinal polypeptide (VIP)-producing neurons in the SCN core. Blocking GABA release from AVP neurons via deletion of the vesicular GABA transporter (Vgat) gene lengthened the activity time (the interval between the onset and offset of locomotor activity) and shortened the duration of high Ca2+ activity in VIP neurons to correspond to the behavioral rest time. Conversely, eliminating functional GABAA receptors (GABAAR) in VIP neurons by in vivo genome editing reduced morning locomotor activity level and shortened the activity time, while lengthening the high Ca2+ duration in VIP neurons. Optogenetic activation of AVP neurons in vivo increased Ca2+ levels in VIP neurons during the night; this effect was significantly reduced in AVP neuron-specific Vgat-deficient mice. A similar Ca2+ response in VIP neurons following AVP neuronal activation was observed in SCN slices and was inhibited by the GABAAR antagonist gabazine. Importantly, gabazine application alone elevated baseline Ca2+ levels in VIP neurons, suggesting tonic GABA-mediated inhibition of these neurons. Moreover, AVP neuronal activation decreased Ca2+ levels in non-AVP neurons located between AVP- and VIP-rich regions of the SCN. These results suggest that GABA released from AVP neurons indirectly disinhibits VIP neurons by suppressing intermediate non-AVP neurons, thereby precisely setting behavioral activity/rest time.

Ocean microbes contribute to biogeochemical cycles and ecosystem function, but they do so under top-down pressure imposed by viruses. While viruses are increasingly understood spatially and beginning to be incorporated into predictive modeling, high-frequency ocean virus dynamics remain understudied due to methodological challenges. Here we sampled stratified Bermuda Atlantic Time Series (BATS) waters for 112 hours at sub-daily 4- (surface) or 12- (deep chlorophyll maximum) hour intervals, purified viral particles from these samples, sequenced their metagenomes, and used the resulting data to characterize high-frequency virus community dynamics. Aggregated community diversity metrics changed with depth, but were not statistically significant temporally at a fixed location. However, finer-scale population-level analyses revealed both depth and temporal change, including physicochemical depth-driven differences and, in surface waters, thousands of viral populations that exhibited statistically significant diel rhythms. Statistical analyses revealed three main archetypes of temporal dynamics that themselves differed in abundance patterns, host predictions, viral taxonomy, and gene functions. Among these, highlights include viruses resembling an archetype with a night peaking pattern in activity that include an over-representation of viruses that putatively infect Prochlorococcus, a phototrophic cyanobacteria. Together, these efforts provide baseline community- and population-scale short-time-frame observations relevant to future climate state modeling.

The autoimmune disease systemic lupus erythematosus (SLE) is associated with genetic variants in the X-linked gene CXORF21, which encodes the protein TASL. TASL acts as an adaptor in the IRF5 pathway and is necessary for the phosphorylation of IRF5 in response to TLR7 or TLR9 stimulation. Here, we investigate the role of TASL in the humoral immune response, and in the development of lupus in the B6.MRLlpr murine model of SLE. We find that while TASL is dispensable for their development, it is required for the full activation of B cells via TLR9 stimulation, and consequent interferon signaling and inflammatory cytokine expression. Additionally, TASL is crucial for the emergence of age-associated B cells (ABCs), a B cell population derived from the extrafollicular response that increases with age and is expanded in autoimmune disease, and the production of IgG2c antibodies. We also find that deletion of TASL prevents the onset of autoimmunity in the genetically-determined B6.MRLlpr model of lupus.

Subcutaneous and visceral adipose depots employ distinct expansion strategies in response to dietary cues, yet the molecular regulators underlying these depot-specific adaptations remain poorly understood. Through integrated proteomic profiling of human subcutaneous and visceral adipose tissues from paired obese/non-obese donors and temporal transcriptomic analysis of mouse adipose stem and progenitor cells (ASPCs) during dietary transitions, we identified Glypican 3 (Gpc3) as an obesity-responsive gene exhibiting reciprocal expression patterns between depots. ASPC-specific Gpc3 deletion in mice amplified high-fat diet-induced weight and fat mass gain, with a selective enhancement of expansion in inguinal white adipose tissue (WAT) without affecting epididymal WAT. Mechanistically, Gpc3 loss biased ASPC fate toward adipogenesis over proliferation through depot-specific modulation of canonical Wnt signaling. These findings establish Gpc3 as a regulator for regional adipose plasticity, offering a molecular target for reprogramming pathological fat distribution in obesity and related metabolic disorders.

Monoclonal antibody therapies are being developed to treat measles in response to its recent resurgence. These therapies risk driving measles virus evolution in ways that might undermine the protection offered by vaccination, outweighing potential benefits.

Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. Previous studies have shown that Mg2+ depletion enables Pseudomonas aeruginosa to become resistant to colistin. Here, we show that magnesium sequestration by Candida albicans also enables P. aeruginosa to evolve a nearly hundredfold higher level of colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway involves early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced colistin binding to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity triggers novel evolutionary trajectories, leading to extremely high colistin resistance in P. aeruginosa.