Search bioRxiv⌕ Search

Biology subjects

Smith, T. P.

Publications and source records attributed to Smith, T. P..

At least 19 recordsLinked to original sources

Prevalence of electricity production among culturable bacteria

Microbial fuel cells (MFCs) technology offers sustainable electricity production. Current research largely focuses on few select model organisms, therefore the true prevalence of exoelectrogenesis amongst bacteria remaining largely unknown. We present a broad-scale survey of monomicrobial electricity production among environmental bacterial isolates inoculated in MFCs, using model organism Shewanella oneidensis MR-1 as a benchmark. Of the assessed taxa, 11-22% displayed exoelectrogenic activity, exceeding current predictions and identifying a further three novel exoelectrogenic species. Phylogenetic analysis based on the 16S sequences enabled the evolutionary relationship between isolates to be visualised, revealing that exoelectrogenesis is non-randomly distributed and phylogenetically conserved. Polarisation studies were implemented, revealing that numerous electron transfer mechanism were being utilised to perform exoelectrogenesis. The results of this study imply that bacterial electricity production is more widespread amongst culturable bacteria than previously estimated, with implications for bioprospecting novel exoelectrogens and predicting electrogenic activity in diverse microbial communities.

microbiology↗

Acetylation of Axonal G3BP1 through ELP3 Accelerates Axon Regeneration

Nerve injury triggers localized translation of axonal mRNAs to respond to injury and nerve regeneration. The core stress granule protein G3BP1 sequesters axonal mRNAs in granules before and after axotomy. G3BP1 granule disassembly can be regulated by post-translational modifications, including phosphorylation of S149 phosphorylation and acetylation of human K376 (mouse K374). Axonal G3BP1 undergoes phosphorylation after axotomy, but acetylation of G3BP1 in axons was unknown. Here we show that rodent G3BP1 undergoes K374 acetylation after axotomy is ELP3-dependent, which enhances axonal protein synthesis, accelerates nerve regeneration, and supports functional recovery. ELP3-depleted neurons exhibit reduced axon growth and increased axonal G3BP1 granules. The proximal axons degenerate rapidly despite maintaining soma connectivity, an effect prevented by expression of acetylmimetic G3BP1.Together, these findings identify G3BP1 acetylation via ELP3 as a critical regulator of both axonal regeneration and neuronal resilience, revealing a post-translational mechanism that links stress granule regulation to neuronal repair and protection.

neuroscience↗

A General Framework for Predicting the Temperature-Dependence of Microbial Interactions

Despite its global importance, our ability to predict the impacts of temperature change on the community dynamics of heterotrophic microbes remains limited. Here, we develop a metabolic trait-based mathematical framework to predict the temperature dependence of pairwise interactions among heterotrophic microbial consumers, accounting for their resource environment and community composition. Applying this framework leads to two general predictions. First, microbial species interactions are typically more thermally sensitive than the underlying metabolic traits. Second, temperature systematically reshapes intra- and interspecific interactions: their variance peaks at intermediate temperatures, while mean interaction strengths increase with warming more rapidly than interspecific interaction strengths. We show that these features of temperature-dependent interactions have far-reaching implications for the temperature responses of community coexistence, diversity, and stability. Our framework provides a mechanistic foundation for predicting how temperature affects the dynamics of heterotrophic microbial communities across diverse biological and environmental contexts. SignificanceCommunities of heterotrophic microbes, including bacteria, archaea, protists, and fungi, play a fundamental role in human health, bioprocessing, and global biogeochemical cycles. Predicting their responses to environmental change is a major challenge, with a key missing link being the effects of temperature on species interactions that ultimately shape community dynamics. By integrating metabolic constraints into consumer-resource theory, we derive general predictions about how interactions among heterotrophic microbial species respond to temperature changes. We show that interactions are more sensitive to warming than individual metabolic traits and undergo systematic temperature-dependent changes that alter community-level coexistence, diversity, and stability. These results hold across diverse environmental contexts and heterotrophic systems, providing a foundation for predicting how microbial community dynamics respond to environmental temperature, from biotechnological applications to natural ecosystems.

ecology↗

Phylogenetic clustering of microbial communities as a biomarker for chemical pollution

Microbial communities play a critical role in ecosystem functioning and offer promising potential as bioindicators of chemical pollution in aquatic environments. Here we examine the responses of both bacterial isolates and microbial communities to a range of pollutants, focusing on the phylogenetic predictability of their responses. We found that bacterial isolates exhibited a strong phylogenetic signal in their growth responses, with closely related taxa responding similarly to chemical stress. In microbial communities, pollutants that significantly impacted isolates also reduced community diversity and growth, causing shifts in community structure toward increased phylogenetic clustering, suggesting environmental filtering. The net relatedness index (NRI) effectively captured these shifts, indicating its potential as a simple metric for monitoring pollution. Our findings highlight the predictability of microbial responses to pollution and suggest that microbial-based bioindicators, coupled with rapid sequencing technologies, could transform environmental monitoring.

microbiology↗

The Role of Metabolic Strategies in Determining Microbial Community Diversity along Temperature Gradients

By conservative estimates, microbes make up about 17% of the worlds biomass and are essential for most ecosystem functions. However, the mechanisms driving the variation in microbial species diversity in response to both natural and anthropogenic temperature gradients remain unclear. In this study, we integrate ecological metabolic theory with a community assembly model to predict that microbial community diversity generally follows a unimodal pattern with temperature. The position and magnitude of peak diversity are determined by interaction-driven species sorting acting on variations in the temperature dependence of carbon use efficiency (CUE) and generalist-specialist tradeoff. Specifically, trait sorting across temperatures favours communities with high mean and low variance in species-level CUEs. We provide empirical evidence supporting our qualitative predictions of the unimodal temperature-diversity pattern along the global geological temperature gradient, which peaks at about 10-15 {degrees}C. Our findings indicate that the response of diversity as well as CUE to temperature of microbial communities can be predicted from relatively feasible life-history trait measurements, paving the way for interlinking microbial community diversity and carbon cycling along spatial and temporal thermal gradients.

ecology↗

Disruption of Core Stress Granule Protein Aggregates Promotes CNS Axon Regeneration

Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in C. elegans, increases axon regeneration in injured neurons, showing spontaneous regeneration. Inhibition of G3BP1 by expression of its acidic or B-domain accelerates axon regeneration after nerve injury, bringing a potential therapeutic intervention to promote neural repair in the peripheral nervous system. Here, we asked if G3BP1 inhibition is a viable strategy to promote regeneration in injured mammalian central nervous system where axons do not regenerate spontaneously. G3BP1 B-domain expression was found to promote axon regeneration in the transected spinal cord provided with a permissive peripheral nerve graft (PNG) as well as in crushed optic nerve. Moreover, a cell-permeable peptide (CPP) to a subregion of B-domain (rodent G3BP1 amino acids 190-208) accelerated axon regeneration after peripheral nerve injury and promoted regrowth of reticulospinal axons into the distal transected spinal cord through a bridging PNG. G3BP1 CPP promoted axon growth from rodent and human neurons cultured on permissive substrates, and this function required alternating Glu/Asp-Pro repeats that impart a unique predicted tertiary structure. The G3BP1 CPP disassembles axonal G3BP1, G3BP2, and FMRP, but not FXR1, granules and selectively increases axonal protein synthesis in cortical neurons. These studies identify G3BP1 granules as a key regulator of axon growth in CNS neurons and demonstrate that disassembly of these granules promotes retinal axon regeneration in injured optic nerve and reticulospinal axon elongation into permissive environments after CNS injury. This work highlights G3BP1 granule disassembly as a potential therapeutic strategy for enhancing axon growth and neural repair. SIGNIFICANCE STATEMENTThe central nervous system (CNS) axon does not have the capacity for spontaneous axon regeneration, as seen in the peripheral nervous system (PNS). We previously showed that stress granule-like aggregates of G3BP1 are present in uninjured PNS axons, and these slow nerve regeneration. We now report that CNS axons contain G3BP1 granules, and G3BP1 granule disassembling strategies promote axon regeneration in the injured sciatic nerve, transected spinal cord with a peripheral nerve graft, and injured optic nerve. Thus, G3BP1 granules are a barrier to axon regeneration and can be targeted for stimulating neural repair following traumatic injury, including in the regeneration refractory CNS.

neuroscience↗

Bacterial responses to complex mixtures of chemical pollutants

Our understanding of how microbes respond to pollutants is almost wholly based on single-species responses to individual chemicals. However, in natural environments, microbes experience the effects of multiple pollutants simultaneously, and their responses to these mixtures of chemicals may not be readily predictable based on their responses to each pollutant in isolation. Here we extended the scope and complexity of previous multi-stressor experiments by assaying the growth of model and non-model strains of bacteria in all 255 combinations of 8 chemical stressors. This approach allowed us to identify fitness effects arising from potential high-order interactions among stressor responses. We found that the bacterial strains responded in different ways to stressor mixtures, which could not be predicted simply from their phylogenetic relatedness. Responses to increasingly complex chemical mixtures were more likely to show a significant deviation from a null model based on the responses to each chemical alone. However, these net responses were mainly driven by lower-order interactions among a small number of chemicals, suggesting a limited role for complex high-order interactions. These results simplify the predictability of microbial populations and communities responding to multiple stressors, paving the way for the development of efficient next-generation eco-toxicological assays.

microbiology↗

AREAdata: a worldwide climate dataset averaged across spatial units at different scales through time

In an era of increasingly cross-discipline collaborative science, it is imperative to produce data resources which can be quickly and easily utilised by non-specialists. In particular, climate data often require heavy processing before they can be used for analyses. Here we describe AREAdata, a free-to-use online global climate dataset, pre-processed to provide the averages of various climate variables across differing administrative units (e.g., countries, states). These are daily estimates, based on the Copernicus Climate Data Stores ERA-5 data, regularly updated to the near-present and provided as direct downloads from our website (https://pearselab.github.io/areadata/). The daily climate estimates from AREAdata are consistent with other openly available data, but at much finer-grained spatial and temporal scales than available elsewhere. AREAdata complements the existing suite of climate resources by providing these data in a form more readily usable by researchers unfamiliar with GIS data-processing methods, and we anticipate these resources being of particular use to environmental and epidemiological researchers.

ecology↗

Generation of lineage-resolved complete metagenome-assembled genomes by precision phasing

Microbial communities in many environments include distinct lineages of closely related organisms which have proved challenging to separate in metagenomic assembly, preventing generation of complete metagenome-assembled genomes (MAGs). The advent of long and accurate HiFi reads presents a possible means to address this challenge by generating complete MAGs for nearly all sufficiently abundant bacterial genomes in a microbial community. We present a metagenomic HiFi assembly of a complex microbial community from sheep fecal material that resulted in 428 high-quality MAGs from a single sample, the highest resolution achieved with metagenomic deconvolution to date. We applied a computational approach to separate distinct haplotype lineages and identified haplotypes of hundreds of variants across hundreds of kilobases of genomic sequence. Analysis of these haplotypes revealed 220 lineage-resolved complete MAGs, including 44 in single circular contigs, and demonstrated improvement in overall assembly compared to error-prone long reads. We report the characterization of multiple, closely-related microbes within a sample with potential to improve precision in assigning mobile genetic elements to host genomes within complex microbial communities.

microbiology↗

The role of competition versus cooperation in microbial community coalescence

New microbial communities often arise through the mixing of two or more separately assembled parent communities, a phenomenon that has been termed "community coalescence". Understanding how the interaction structures of complex parent communities determine the outcomes of coalescence events is an important challenge. While recent work has begun to elucidate the role of competition in coalescence, that of cooperation, a key interaction type commonly seen in microbial communities, is still largely unknown. Here, using a general consumer-resource model, we study the combined effects of competitive and cooperative interactions on the outcomes of coalescence events. In order to do so, we simulate coalescence events between pairs of communities with different degrees of competition for shared carbon resources and cooperation through cross-feeding on leaked metabolic by-products (facilitation). We also study how structural and functional properties of post-coalescence communities evolve when they are subjected to repeated coalescence events. We find that in coalescence events, the less competitive and more cooperative parent communities contribute a higher proportion of species to the new community, because this endows superior ability to deplete resources and resist invasions. Consequently, when a community is subjected to repeated coalescence events, it gradually evolves towards being less competitive and more cooperative, as well as more species rich, robust and efficient in resource use. Encounters between microbial communities are becoming increasingly frequent as a result of anthropogenic environmental change, and there is great interest in how the coalescence of microbial communities affects environmental and human health. Our study provides new insights into the mechanisms behind microbial community coalescence, and a framework to predict outcomes based on the interaction structures of parent communities. Author summaryIn nature, new microbial communities often arise from the fusion of whole, previously separate communities (community coalescence). Despite the crucial role that interactions among microbes play in the dynamics of complex communities, our ability to predict how these affect the outcomes of coalescence events remains limited. Here, using a general mathematical model, we study how the structure of species interactions confers an advantage upon a microbial community when it encounters another, and how communities evolve after undergoing repeated coalescence events. We find that competitive interactions between species preclude their survival upon a coalescence event, while cooperative interactions are advantageous for post-coalescence survival. Furthermore, after a community is exposed to many coalescence events, the remaining species become less competitive and more cooperative. Ultimately, this drives the community evolution, yielding post-coalescence communities that are more species-rich, productive, and resistant to invasions. There are many potential environmental and health implications of microbial community coalescence, which will benefit from the theoretical insights that we offer here about the fundamental mechanisms underlying this phenomenon.

ecology↗

Latent functional diversity may accelerate microbial community responses to environmental fluctuations

How complex microbial communities respond to climatic fluctuations remains an open question. Due to their relatively short generation times and high functional diversity, microbial populations harbor great potential to respond as a community through a combination of strain-level phenotypic plasticity, adaptation, and species sorting. However, the relative importance of these mechanisms remains unclear. We conducted a laboratory experiment to investigate the degree to which bacterial communities can respond to changes in environmental temperature through a combination of phenotypic plasticity and species sorting alone. We grew replicate soil communities from a single location at six temperatures between 4{degrees}C and 50{degrees}C. We found that phylogenetically- and functionally-distinct communities emerge at each of these temperatures, with K-strategist taxa favoured under cooler conditions, and r-strategist taxa under warmer conditions. We show that this dynamic emergence of distinct communities across a wide range of temperatures (in essence, community-level adaptation), is driven by the resuscitation of latent functional diversity: the parent community harbors multiple strains pre-adapted to different temperatures that are able to "switch on" at their preferred temperature without immigration or adaptation. Our findings suggest that microbial community function in nature is likely to respond rapidly to climatic temperature fluctuations through shifts in species composition by resuscitation of latent functional diversity.

ecology↗

Desert Dingo (Canis lupus dingo) genome provides insights into their role in the Australian ecosystem.

The dingo is Australias iconic top-order predator and arrived on the continent between 5,000-8,000 years ago. To provide an unbiased insight into its evolutionary affiliations and biological interactions, we coupled long-read DNA sequencing with a multiplatform scaffolding approach to produce an ab initio genome assembly of the desert dingo (85X coverage) we call CanLup_DDS. We compared this genome to the Boxer (CanFam3.1) and German Shepherd dog (CanFam_GSD) assemblies and characterized lineage-specific and shared genetic variation ranging from single- to megabase pair-sized variants. We identified 21,483 dingo-specific and 16,595 domestic dog-specific homozygous structural variants mediating genic and putative regulatory changes. Comparisons between the dingo and domestic dog builds detected unique inversions on Chromosome 16, structural variations in genes linked with starch metabolism, and seven differentially methylated genes. To experimentally assess genomic differences 17 dingoes and 15 German Shepherd dogs were fed parallel diets for 14 days. In dingoes, low AMY2B copy number and serum amylase levels are linked with high cholesterol and LDL levels. Gut microbiome analyses revealed enrichment of the family Clostridiaceae, which can utilize complex resistant starch, while scat metabolome studies identified high phenylethyl alcohol concentrations that we posit are linked with territory marking. Our study provides compelling genomic, microbiome, and metabolomic links showing the dingo has distinct physiology from domestic breed dogs with a unique role in the ecosystem.

genomics↗

Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs

Proteins generated by localized mRNA translation in axons support nerve regeneration through retrograde injury signaling and localized axon growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional control of localized mRNAs, but only a limited number of axonal RBPs have been reported. We used a targeted mass spectrometry approach to profile the axonal RBPs in naive, injured and regenerating PNS axons. We detected 76 axonal proteins that are reported to have RNA binding activity, with the levels of several of these axonal RBPs changing with axonal injury and regeneration. These axonal RBPs with altered axoplasm levels include KHSRP that we previously reported decreases neurite outgrowth in developing CNS neurons. We show that KHSRP levels rapidly increase in sciatic nerve axons after crush injury and remain elevated increasing in levels out to 28 days post-sciatic nerve crush injury. Khsrp mRNA localizes into axons and the rapid increase in axonal KHSRP after axotomy is mediated by the local translation of its mRNA. KHSRP binds to mRNAs with a 3UTR AU-rich element and targets those mRNAs to the cytoplasmic exosome for degradation. KHSRP knockout mice show increased axonal levels of defined KHSRP target mRNAs, Gap43 and Snap25 mRNAs, following sciatic nerve injury and accelerated nerve regeneration in vivo. These data indicate that axonal translation of Khsrp mRNA following nerve injury serves to destabilize other axonal mRNAs and slow axon regeneration.

neuroscience↗

Systematic variation in the temperature dependence of bacterial carbon use efficiency

Understanding the temperature dependence of carbon use efficiency (CUE) is critical for understanding microbial physiology, population dynamics, and community-level responses to changing environmental temperatures 1,2. Currently, microbial CUE is widely assumed to decrease with temperature 3,4. However, this assumption is based largely on community-level data, which are influenced by many confounding factors 5, with little empirical evidence at the level of individual strains. Here, we experimentally characterise the CUE thermal response for a diverse set of environmental bacterial isolates. We find that contrary to current thinking, bacterial CUE typically responds either positively to temperature, or has no discernible temperature response, within biologically meaningful temperature ranges. Using a global data-synthesis, we show that our empirical results are generalisable across a much wider diversity of bacteria than have previously been tested. This systematic variation in the thermal responses of bacterial CUE stems from the fact that relative to respiration rates, bacterial population growth rates typically respond more strongly to temperature, and are also subject to weaker evolutionary constraints. Our results provide fundamental new insights into microbial physiology, and a basis for more accurately modelling the effects of shorter-term thermal fluctuations as well as longer-term climatic warming on microbial communities.

microbiology↗

Haplotype-Resolved Cattle Genomes Provide Insights Into Structural Variation and Adaptation

We present high quality, phased genome assemblies representative of taurine and indicine cattle, subspecies that differ markedly in productivity-related traits and environmental adaptation. We report a new haplotype-aware scaffolding and polishing pipeline using contigs generated by the trio binning method to produce haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle breeds. These assemblies were used to identify structural and copy number variants that differentiate the subspecies and we found variant detection was sensitive to the specific reference genome chosen. Six gene families with immune related functions are expanded in the indicine lineage. Assembly of the genomes of both subspecies from a single individual enabled transcripts to be phased to detect allele-specific expression, and to study genome-wide selective sweeps. An indicus-specific extra copy of fatty acid desaturase is under positive selection and may contribute to indicine adaptation to heat and drought.

genomics↗

Adaptive evolution explains the present-day distribution of the thermal sensitivity of population growth rate

Developing a thorough understanding of how ectotherm physiology adapts to different thermal environments is of crucial importance, especially in the face of global climate change. A key aspect of an organisms thermal performance curve--the relationship between fitness-related trait performance and temperature--is its thermal sensitivity, i.e., the rate at which trait values increase with temperature within its typically-experienced thermal range. For a given trait, the distribution of thermal sensitivities across species, often quantified as "activation energy" values, is typically right-skewed. Currently, the mechanisms that generate this distribution are unclear, with considerable debate about the role of thermodynamic constraints vs adaptive evolution. Here, using a phylogenetic comparative approach, we study the evolution of the thermal sensitivity of population growth rate across phytoplankton (Cyanobacteria and eukaryotic microalgae) and prokaryotes (bacteria and archaea), two microbial groups that play a major role in the global carbon cycle. We find that thermal sensitivity across these groups is moderately phylogenetically heritable, and that its distribution is shaped by repeated evolutionary convergence throughout its parameter space. More precisely, we detect bursts of adaptive evolution in thermal sensitivity, increasing the amount of overlap among its distributions in different clades. We obtain qualitatively similar results from evolutionary analyses of the thermal sensitivities of two physiological rates underlying growth rate: net photosynthesis and respiration of plants. Furthermore, we find that these episodes of evolutionary convergence are consistent with two opposing forces: decrease in thermal sensitivity due to environmental fluctuations and increase due to adaptation to stable environments. Overall, our results indicate that adaptation can lead to large and relatively rapid shifts in thermal sensitivity, especially in microbes where rapid evolution can occur at short time scales. Thus, more attention needs to be paid to elucidating the implications of rapid evolution in organismal thermal sensitivity for ecosystem functioning. Author summaryChanges in environmental temperature influence the performance of biological traits (e.g., respiration rate) in ectotherms, with the relationship between trait performance and temperature (the "thermal performance curve") being single-peaked. Understanding how thermal performance curves adapt to different environments is important for predicting how organisms will be impacted by climate change. One key aspect of the shape of these curves is the thermal sensitivity near temperatures typically experienced by the species. Whether and how thermal sensitivity responds to different environments is a topic of active debate. To shed light on this, here we perform an evolutionary analysis of the thermal sensitivity of three key traits of prokaryotes, phytoplankton, and plants. We show that thermal sensitivity does not evolve in a gradual manner, but can differ considerably even between closely related species. This suggests that thermal sensitivity undergoes rapid adaptive evolution, which is further supported by our finding that thermal sensitivity varies weakly with latitude. We conclude that variation in thermal sensitivity arises partly from adaptation to environmental factors and that this may need to be accounted for in ecophysiological models.

evolutionary biology↗

An improved pig reference genome sequence to enable pig genetics and genomics research

The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete and unresolved redundancies, short range order and orientation errors and associated misassembled genes limited its utility. We present two annotated highly contiguous chromosome-level genome assemblies created with more recent long read technologies and a whole genome shotgun strategy, one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. These highly contiguous assemblies plus annotation of a further 11 short read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.

genomics↗

Metabolic rates of prokaryotic microbes may inevitably rise with global warming

Understanding how the metabolic rates of prokaryotes respond to temperature is fun-damental to our understanding of how ecosystem functioning will be altered by climate change, as these micro-organisms are major contributors to global carbon efflux. Ecological metabolic theory suggests that species living at higher temperatures evolve higher growth rates than those in cooler niches due to thermodynamic constraints. Here, using a global prokaryotic dataset, we find that maximal growth rate at thermal optimum increases with temperature for mesophiles (temperature optima [lsim] 45{degrees}C), but not thermophiles ({gtrsim} 45{degrees}C). Furthermore, short-term (within-day) thermal responses of prokaryotic metabolic rates are typically more sensitive to warming than those of eukaryotes. Given that climatic warming will mostly impact ecosystems in the mesophilic temperature range, we conclude that as microbial communities adapt to higher temperatures, their metabolic rates and therefore, carbon efflux, will inevitably rise. Using a mathematical model, we illustrate the potential global impacts of these findings.

ecology↗