Biology subjects

Lang, P.

Publications and source records attributed to Lang, P..

8 recordsLinked to original sources

bioRxiv2025

Rapid adaptation and extinction across climates in synchronized outdoor evolution experiments of Arabidopsis thaliana

Climate change is threatening species with extinction, and rapid evolutionary adaptation may be their only option for population rescue over short ecological timescales. However, direct observations of rapid genetic adaptation and population dynamics across climates are rare across species. To fill this gap, we conducted a replicated, globally synchronized evolution experiment with the plant Arabidopsis thaliana for 5 years in over 30 outdoor experimental gardens with distinct climates across Europe, the Levant, and North America. We performed whole-genome sequencing on [~]70,000 surviving reproductive individuals and directly observed rapid and repeatable adaptation across climates. Allele frequency changes over time were parallel in experimental evolution replicates within the same climates, while they diverged across contrasting climates--with some allele frequency shifts best explained by strong selection between -46% to +60%. Screening the genome for signals of rapid climate adaptation identified a polygenic architecture with both known and novel adaptive genetic variants connected to important ecological phenotypes including environmental stress responses, CAM5 and HEAT SHOCK FACTORs, and germination and spring flowering timing, CYTOCHROME P450s and TSF. We found evolutionary adaptation trends were often predictable, but variable across environments. In warm climates, high evolutionary predictability was associated with population survival up to 5 years, while erratic trends were an early warning for population extinction. Together, these results show rapid climate adaptation may be possible, but understanding its limits across species will be key for biodiversity forecasting.

evolutionary biology↗

bioRxiv2021

Standing genetic variation fuels rapid evolution of herbicide resistance in blackgrass

Repeated herbicide applications exert enormous selection on blackgrass (Alopecurus myosuroides), a major weed in cereal crops of the temperate climate zone including Europe. This inadvertent large-scale experiment gives us the opportunity to look into the underlying genetic mechanisms and evolutionary processes of rapid adaptation, which can occur both through mutations in the direct targets of herbicides and through changes in other, often metabolic, pathways, known as non-target-site resistance. How much either type of adaptation relies on de novo mutations versus pre-existing standing variation is important for developing strategies to manage herbicide resistance. We generated a chromosome-level reference genome for A. myosuroides for population genomic studies of herbicide resistance and genome-wide diversity across Europe in this species. Bulked-segregant analysis evidenced that non-target-site resistance has a complex genetic architecture. Through empirical data and simulations, we showed that, despite its simple genetics, target-site resistance mainly results from standing genetic variation, with only a minor role for de novo mutations.

evolutionary biology↗

bioRxiv2021

Quantifying the scale of genetic diversity extinction in the Anthropocene

More species than ever before are at risk of extinction due to anthropogenic habitat loss and climate change. But even species that are not threatened have seen reductions in their populations and geographic ranges, likely impacting their genetic diversity. Although preserving genetic diversity is key to maintaining adaptability of species, we lack predictive tools and global estimates of genetic diversity loss across ecosystems. By bridging theories of biodiversity and population genetics, we introduce a mathematical framework to understand the loss of naturally occurring DNA mutations within decreasing habitat within a species. Analysing genome-wide variation data of 10,095 geo-referenced individuals from 20 plant and animal species, we show that genome-wide diversity follows a power law with geographic area (the mutations-area relationship), which can predict genetic diversity loss in spatial computer simulations of local population extinctions. Given pre-21st century values of ecosystem transformations, we estimate that over 10% of genetic diversity may already be lost, surpassing the United Nations targets for genetic preservation. These estimated losses could rapidly accelerate with advancing climate change and habitat destruction, highlighting the need for forecasting tools that facilitate implementation of policies to protect genetic resources globally.

ecology↗

bioRxiv2020

Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2

The ongoing coronavirus disease 2019 (COVID-19) pandemic has raised an urgent need to develop effective therapeutics against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a potential antiviral drug target, the nucleocapsid (N) protein of SARS-CoV-2 functions as a viral RNA chaperone and plays vital and multifunctional roles during the life cycle of coronavirus1-3. In this study, we discovered that the N protein of SARS-CoV-2 undergoes liquid-liquid phase separation (LLPS) both in vitro and in vivo, which is further modulated by viral RNA. In addition, we found that, the core component of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, nsp12, preferentially partitions into the N protein condensates. Moreover, we revealed that, two small molecules, i.e., CVL218 and PJ34, can be used to intervene the N protein driven phase separation and loosen the compact structures of the condensates of the N-RNA-nsp12 complex of SARS-CoV-2. The discovery of the LLPS-mediated interplay between N protein and nsp12 and the corresponding modulating compounds illuminates a feasible way to improve the accessibility of antiviral drugs (e.g., remdesivir) to their targets (e.g., nsp12/RdRp), and thus may provide useful hints for further development of effective therapeutic strategies against SARS-CoV-2.

biophysics↗

bioRxiv2019

Viral infection overcomes ineffectiveness of anti-tumoral CD8+ T cell mediated cytotoxicity

With the integration of PD-1 and CTLA-4 targeting immune checkpoint blockade into cancer treatment regimes, the anti-tumoral cytotoxicity of tumor-specific CD8+ T cells is well established. However, while the unresponsiveness of CD8+ T cells against big tumors is mainly explained by T cell exhaustion, other factors contributing to CD8+ T cell failure remain not well studied. Here we used a mouse melanoma model to study the interaction of growing tumor cells, innate immunity and CD8+ T cell responses induced by viral replication. Mouse model of melanoma (B16F10-OVA) and infections with arenaviruses. Growing B16F10-OVA cells did not induce systemic ablation of tumor specific CD8+ T cells. However, despite the presence of tumor-infiltrating CD8+ T cells, the anti-tumoral immune response was very limited. T cell anergy against the tumor was accompanied with a strong down-regulation of MHC-I on advanced tumors. LCMV infection restored the MHC class I expression, enhanced T cell function and lead to tumor regression. This study shows that tumor progression does not necessary lead to systemic exhaustion of the anti-tumoral CD8+ T cell response. Lack of innate signals is an additional reason for limited CD8+ T cell mediated cytotoxicity against the tumor.

immunology↗

bioRxiv2017

Exploring variation in human papillomavirus vaccination uptake: multi-level spatial analysis

BackgroundUnderstanding the factors that influence human papillomavirus (HPV) vaccination uptake is critically important to design effective vaccination programmes. In Switzerland, completed HPV vaccination by age 16 years among women ranges from 30 to 79% across 26 cantons (states). Our objective was to identify factors that are associated with the spatial variation in HPV vaccination uptake.\n\nMethods and findingsWe used data from the Swiss National Vaccination Coverage Survey 2009-2016 on HPV vaccination status ([≥]1 dose) of 14-17 year old girls, their municipality of residence and their nationality for 21 of 26 cantons (N=8,965). We examined covariates at municipality level: language, degree of urbanisation, socio-economic position, religious denomination, results of a vote about vaccination laws; and, at cantonal level, availability of school-based vaccination and survey period. We used a series of conditional auto regressive (CAR) models to assess the effects of covariates while accounting for variability between cantons and municipal-level spatial autocorrelation. In the best-fit model, school-based vaccination (adjusted odds ratio, OR: 2.51, 95% credible interval, CI: 1.77-3.56) was associated with increased uptake, while lower acceptance of vaccination laws was associated with lower HPV vaccination uptake (OR 0.61, 95% CI: 0.50-0.73). Overall, the covariates explained 88% of the municipal-level variation in uptake.\n\nConclusionsIn Switzerland, cantons play a prominent role in the variation in HPV vaccination uptake, especially through the provision of school-based vaccination delivery. HPV vaccination uptake is also strongly associated with inhabitants attitudes towards vaccination. To increase uptake, efforts should be made both to mitigate vaccination scepticism and to encourage school-based vaccination.

epidemiology↗

bioRxiv2017

A rainfall-manipulation experiment with 517 Arabidopsis thaliana accessions

The gold standard for studying natural selection and adaptation in the wild is to quantify lifetime fitness of individuals from natural populations that have been grown together in a common garden, or that have been reciprocally transplanted. By combining fitness values with species traits and genome sequences, one can infer selection coefficients at the genetic level. Here we present a rainfall-manipulation experiment with 517 whole-genome sequenced natural accessions of the plant Arabidopsis thaliana spanning the global distribution of the species. The experiments were conducted in two field stations in contrasting climates, in the Mediterranean and in Central Europe, where we built rainout shelters and simulated high and low rainfall. Using custom image analysis we quantified fitness- and phenology-related traits for 23,154 pots, which contained about 14,500 plants growing independently, and over 310,000 plants growing in small populations (max. 30 plants). This large field experiment dataset, which associates fitness and ecologically-relevant traits with genomes, will provide an important resource to test eco-evolutionary genetic theories and to understand the potential evolutionary impacts of future climates on an important plant model species.

evolutionary biology↗

bioRxiv2017

A Role For The F-Box Protein HAWAIIAN SKIRT In Plant miRNA Function

As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. While a plethora of factors involved in their biogenesis and action in Arabidopsis thaliana have been described, these processes and their fine-tuning are not fully understood in plants. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156 activity. We identified a new mutant allele of the F-box protein HAWAIIAN SKIRT (HWS; At3G61590), hws-5, as a suppressor of the MIM156-induced developmental and molecular phenotypes. In hws plants, levels of endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS - but not a truncated version lacking the F-box domain - display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants, hws loses its delayed floral organ abscission ( skirt) phenotype, suggesting epistasis. Also, the overall hws transcriptome profile partially resembles well-known miRNA mutants hyl1-2 and se-3, indicating action in a common pathway. We thus propose HWS as a novel, F-box dependent regulator of miRNA biogenesis.\n\nSummary statementHAWAIIAN SKIRT is a regulator of Arabidopsis thaliana microRNA biogenesis and acts in an F-box-dependent manner.

plant biology↗