Biology subjects

West, G.

Publications and source records attributed to West, G..

11 recordsLinked to original sources

bioRxiv2025

A database of biological thermal performances

We built a database of thermal performance curves that includes different variables --mostly population growth rates --for species in representative groups across major domains, including viruses, bacteria, archaea, unicellular eukaryotes (such as fungi), and multicellular eukaryotes (including plants and both invertebrates and vertebrates). To build the database, we integrated previous databases and compiled additional data from individual studies, all of which were normalized to the same units when corresponding. Our database contains data for 1300 curves across 1125 different species and 38 variable types. The database consists of four (.csv) tables and an R code that can be explored through an R package or a Shiny app. Applications of our dataset include providing a resource to studies in thermal ecology and integration with other types of data, such as geographic temperatures. This would allow us to make further predictions, such as potential species distributions based on their thermal tolerances and their changes with climate warming.

bioinformatics↗

bioRxiv2025

Scaling laws in biological thermal performances

Understanding the extent to which genetic correlations change in response to environmental factors, such as temperature, is a poorly explored question, despite the importance of understanding how different processes will change with climate warming. Despite correlations between thermal performance traits having been reported in the literature for a few taxa and performance tasks, such as population growth rate, a comprehensive global analysis of the entire tree of life and multiple performance tasks remains an open challenge. To advance in this open question, we compile a database of 1,300 thermal response curves, encompassing 38 variable types related to individuals performance (including per capita population growth rate, photosynthetic rate, among others) and 1,125 different species, ranging from viruses to mammals, encompassing all major lineages of the tree of life. Our analysis reveals that among all possible relationships between traits and optimal performance, four traits form a line with a high goodness-of-fit, while the remaining traits exhibit a polygonal pattern, either a triangle or a tetrahedron. We derive a thermodynamic framework that explains the relationships described by a curve or line (as opposed to a surface or polygon), highlighting the linear relationship between maximum and minimum temperatures, as well as between maximum and optimum temperatures. We also discuss other generic trait evolution models, which could account for the other significant sublinear relationships, as well as the more general model, Pareto optimality theory, which could account for relationships in the form of lines or polygons. Our theoretical framework and empirical evidence suggest that, based on a single data point (e.g., minimum temperature), all critical temperature limits and maximum performance boundaries can be predicted using the estimated parameter from this study. Our results reveal universal scaling relationships in thermal performance, which could be useful for predicting changes in performance under scenarios of climate warming.

biophysics↗

bioRxiv2025

A general model for genomic traits evolution

A large body of data indicates that genomic elements, including gene families and entire genomes, exhibit diverse types of evolutionary dynamics. Several models have been developed to describe the dynamics of, for example, genome size; however, a simple deterministic model with interpretable parameters that could be useful for fitting a variety of data remains an open problem. Here, we show that (a continuous form of) the Breeders equation for the evolution of quantitative traits/characters leads to a general model that explains the dynamics of genomic elements generated by indel mutations (duplications, insertions, and deletions) and selection. Our framework consists of a general exponential-linear model that predicts at least six different types of dynamical behaviors, including exponential growth and decay. The equations fit data, such as evolution experiments across generations, field observational data of genome sizes across time, and data from phylogenetic reconstructions of ancestral states of genome size across millions of years of a variety of taxa, including viruses, bacteria, fungi, unicellular eukaryotes, plants, and animals, at both intra- and interspecific levels. To test the universality of the dynamics, we derived a dimensionless equation that enables the (re)scaling and subsequent collapse of all data for growth or decay onto a single universal curve. Thus, our model provides a general basis not only for explaining the dynamics in the size of gene families or whole genomes of populations across taxonomic and environmental scales, but also other traits, providing a foundation for further theoretical developments.

evolutionary biology↗

bioRxiv2025

Does genetic rescue disrupt local adaptation? An experimental test using thermally adapted Tribolium castaneum lines

Anthropogenic drivers are restricting many species to small, genetically isolated populations. These are prone to inbreeding depression and are at an increased risk of extinction. Genetic rescue, the controlled introduction of genetic variation from another population, can alleviate inbreeding effects. A major conservation concern, restricting the use of this technique, is that such augmented gene flow may disrupt local adaptation crucial to a populations persistence. Using populations of the red flour beetle (Tribolium castaneum) experimentally adapted to reproduce at higher temperatures, we assess whether genetic rescue attempts disrupt thermal adaptation. Rescuers, drawn from populations adapted to either 30{degrees}C or 38{degrees}C, were introduced into populations adapted to 38{degrees}C, which had been inbred for two generations. We recorded population productivity for three generations post-rescue, in the adapted 38{degrees}C environment. Rescuers with and without local adaptation significantly increased the productivity of recipient inbred populations but, importantly, those sharing local adaptation to reproduction at 38{degrees}C provided greater increases in productivity. For the first time, we show that co-adaptation between rescuing individuals and rescuee population maybe an essential aspect of achieving desired conservation outcomes.

evolutionary biology↗

bioRxiv2025

COVID-19 vaccination induces cross-neutralisation of sarbecoviruses related to SARS-CoV-2

Close relatives of SARS-CoV-1 and SARS-CoV-2 continue to circulate in wildlife, posing an ongoing threat of zoonotic spillover. While vaccination played a key role in controlling the COVID-19 pandemic, variants of concern (VOC) with immune evasive substitutions emerged on multiple occasions, causing widespread breakthrough infections. The combined threats of zoonosis and newly emerging VOCs, coupled with the potential for recombination, underscore the need to assess the breadth of existing vaccine-mediated protection. Here, we investigate a cohort of older individuals (median age 68.5 years) for the potential of cross-neutralisation against Omicron lineage VOC and animal sarbecoviruses induced by four COVID-19 vaccine doses. Despite the recent use of a bivalent mRNA vaccine dose (encoding spike from Wu-1 and omicron), we observed that neutralisation of Omicron lineage VOCs such as BA.1 and BA.2 were reduced compared to SARS-CoV-2 Wu-1, suggesting an imprinted immune response from pre-Omicron lineage viruses. Similarly, both SARS-CoV-1 and a SARS-CoV-1-related bat CoV were neutralised less efficiently than SARS-CoV-2 Wu-1. Unexpectedly, however, we observed that two animal SARS-CoV-2-related viruses, BANAL-20-52 (from bats) and a pangolin-CoV, were more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-protection against certain animal sarbecoviruses.

microbiology↗

bioRxiv2024

Sexual selection matters in genetic rescue, but productivity benefits fade over time; a multi-generation experiment to inform conservation.

Globally, many species are threatened by population decline because of anthropogenic changes which leads to population fragmentation, genetic isolation, and inbreeding depression. Genetic rescue, the controlled introduction of genetic variation, is a method used to potentially relieve such effects in small populations. However, without understanding how the characteristics of rescuers impact rescue attempts interventions run the risk of being sub-optimal, or even counterproductive. We use the Red Flour Beetle (Tribolium castaneum) to test the impact of rescuer sex, and sexual selection background, on population productivity. We record the impact of genetic rescue on population productivity in 24/36 replicated populations for ten generations following intervention. We find little or no impact of rescuer sex on the efficacy of rescue but show that a background of elevated sexual selection makes individuals more effective rescuers. In both experiments, rescue effects diminish 6-10 generations after the rescue. Our results confirm that the efficacy of genetic rescue can be influenced by characteristics of the rescuers and that the level of sexual selection in the rescuing population is an important factor. We show that any increase in fitness associated with rescue may last for a limited number of generations, suggesting implications for conservation policy and practice.

evolutionary biology↗

bioRxiv2024

Functionality of BRCA1 supports the survival of prostate cancer cells during the development of castration resistance

Androgen deprivation therapy (ADT; castration) is the main treatment option for metastatic prostate cancer (PCa), but eventually, castration-resistant prostate cancer (CRPC) develops with no curative treatments. In CRPC, more than 20% of men carry mutations in DNA damage response (DDR) genes, including BRCA1/2. In this study, we elucidated the prostate tissue-specific functional role of BRCA1 protein. Our results indicate that DDR is dynamically regulated by androgen receptor (AR) signaling, and AR activation by the natural ligand dihydrotestosterone strongly downregulates the expression of BRCA1 in multiple cell lines. Consistent with these findings, our analyses of patient samples and mouse xenografts showed that DNA damage and BRCA1 expression were sustained after ADT. With unbiased mass spectrometry and bioinformatics approaches as well as experimentally, we found that BRCA1 interacts with Raptor, an mTORC1 component, and regulates the mTOR signaling pathway and PCa growth in vitro. Furthermore, we found that mTOR inhibition reduced the recruitment of DDR proteins, BRCA1 and Rad51, to DNA damage sites, creating a vulnerability towards DNA damage-inducing androgen deprivation. Moreover, we observed that BRCA1 supported ADT-induced activation of the oxidative stress sensor NRF2. Our findings shed further light on the complex DDR-AR interplay in PCa and suggest that, during PCa progression, BRCA1 expression may be retained due to the beneficial modulation of mTORC1 signaling in the AR environment by BRCA1. SignificanceAndrogen receptor activation acts as a strong suppressor of BRCA1. Consequently, androgen deprivation activates BRCA1, which in turn promotes survival in castration resistance by supporting mTOR signaling and NRF2-mediated antioxidant processes.

cancer biology↗

bioRxiv2024

Fluorinated trehalose analogues for cell surface engineering and imaging of Mycobacterium tuberculosis

The sensitive, rapid and accurate diagnosis of Mycobacterium tuberculosis (Mtb) infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year. To overcome these limitations there is an urgent need for next-generation TB diagnostic technologies. Here we report the use of a discrete panel of native 19F-trehalose (F-Tre) analogues to label and directly visualise Mtb by exploiting the uptake of fluorine-modified trehalose analogues via the mycobacterial trehalose LpqY-SugABC ATP-binding cassette (ABC) importer. We discovered the extent of modified F-Tre uptake correlates with LpqY substrate recognition and characterisation of the interacting sites by saturation transfer difference NMR coupled with molecular dynamics provides a unique glimpse into the molecular basis of fluorine-modified trehalose import in Mtb. Lipid profiling demonstrated that F-Tre analogues modified at positions 2, 3 and 6 are incorporated into mycobacterial cell-surface trehalose-containing glycolipids. This rapid one-step labelling approach facilitates the direct visualisation of F-Tre-labelled Mtb by focused ion beam (FIB) secondary ion mass spectrometry (SIMS), enabling pathogen specific detection. Collectively, our findings highlight that F-Tre analogues have potential as tools to probe and unravel Mtb biology and can be exploited to detect and image TB.

microbiology↗

bioRxiv2024

Clonal Parabacteroides from Gut Microfistulous Tracts as Transmissible Cytotoxic Succinate-Commensal Model of Crohn's Disease Complications

Crohns disease (CD) has been traditionally viewed as a chronic inflammatory disease that cause gut wall thickening and complications, including fistulas, by mechanisms not understood. By focusing on Parabacteroides distasonis (presumed modern succinate-producing commensal probiotic), recovered from intestinal microfistulous tracts (cavernous fistulous micropathologies CavFT proposed as intermediate between mucosal fissures and fistulas) in two patients that required surgery to remove CD-damaged ilea, we demonstrate that such isolates exert pathogenic/pathobiont roles in mouse models of CD. Our isolates are clonally-related; potentially emerging as transmissible in the community and mice; proinflammatory and adapted to the ileum of germ-free mice prone to CD-like ileitis (SAMP1/YitFc) but not healthy mice (C57BL/6J), and cytotoxic/ATP-depleting to HoxB8-immortalized bone marrow derived myeloid cells from SAMP1/YitFc mice when concurrently exposed to succinate and extracts from CavFT-derived E. coli, but not to cells from healthy mice. With unique genomic features supporting recent genetic exchange with Bacteroides fragilis-BGF539, evidence of international presence in primarily human metagenome databases, these CavFT Pdis isolates could represent to a new opportunistic Parabacteroides species, or subspecies ( cavitamuralis) adapted to microfistulous niches in CD.

genomics↗

bioRxiv2022

Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress

The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by LMNA gene, has been shown to contribute towards altered gene expression during heat shock, but the underlying mechanisms are poorly understood. Here we show that reversible lamin A/C phosphorylation at Ser22 upon HS is an evolutionary conserved stress response that is triggered in concert with HSF1 activation in human and mouse cells and can also be observed in D. melanogaster in vivo. Consequently, the phosphorylation increase facilitated nucleoplasmic localization of lamin A/C and nuclear rounding in response to HS. The importance of lamin phosphorylation equilibria in HS was confirmed by lamin A/C knock-out (KO) cells that showed deformed nuclei after HS and were rescued by ectopic expression of wild-type, but not by a phosphomimetic (S22D) lamin A mutant. Furthermore, HS triggered release of lamina-associated protein 2 (Lap2) from its association with lamin A/C and concurrently its downregulation, a response that was perturbed in lamin A/C KO cells and in LMNA mutant patient fibroblasts. The abrogated Lap2 response resulted in impaired cell cycle arrest under HS and compromised survival at the recovery. Taken together, our results suggest that the altered phosphorylation stoichiometry of lamin A/C provides an evolutionary conserved mechanism to regulate lamin structure and serve nuclear adaptation and cell survival during HS.

molecular biology↗

bioRxiv2021

A general model for temperature-dependence in biology

At present, there is no simple, complete, and first principles-based model for quantitatively describing the full range of observed biological temperature responses. Here, we derive a theory exhibiting these features based on the Eyring-Evans-Polanyi theory governing chemical reaction rates, and which is applicable across all scales from the micro to the macro. Assuming only that the conformational entropy of molecules changes with temperature, we derive a theory for the temperature dependence which takes the form of an exponential function modified by a power-law. Our framework leads to six deductions applicable to any biological trait that depends on temperature, and elucidates novel aspects of universal temperature responses across the tree of life, from quantum to classical scales. All predictions are well supported by data for a wide variety of biological rates and steady states, from molecular to ecological scales and across multiple taxonomic groups. In addition, we provide novel explanations of several empirical relationships including optimal values in temperature response curves. One-Sentence SummaryWe derive a simple and universal formulae to characterize temperature responses of biological processes across the tree of life.

ecology↗