Biology subjects

Rathmann, I.

Publications and source records attributed to Rathmann, I..

4 recordsLinked to original sources

bioRxiv2025

Additive effects of environmental and demographic variation shape the repeatability of evolution across replicated experiments

The repeatability of evolution is fundamentally important for understanding the origin and diversification of life as well as for developing evolutionary forecasting tools. Repeatability is limited by stochasticity, here defined as changes that are independent of genotypic fitness effects. Over short timescales, the two main sources of stochasticity of evolutionary change are environmental stochasticity and demographic (life-history) stochasticity. Quantifying the relative importance of these two sources of stochasticity in driving fitness outcomes is crucially important for predicting evolutionary responses. To gain insights in the effects of stochasticity, five institutes replicated an evolutionary experiment exposing Caenorhabditis elegans to novel rearing conditions. Replication across the institutes led to variation in selective environments, e.g. through divergent microbiomes among institutes. Replication within institutes was done across demographic treatments that influence the potential for population-size dependent fluctuations in allele frequencies (drift) and genetic hitchhiking (draft). We found high among-institute variation in fitness outcomes, which was partially explained by variation in microbiota. Whereas lab-specific effects explained most of the variance in mean fitness, the repeatability of fitness outcomes depended more on demographic heterogeneity. Specifically, population bottlenecks resulted in high among-replicate variation in fitness. When combined, environmental and demographic stochasticity additively reduced repeatability, underlining their additive importance in developing evolutionary forecasting tools. These results further highlight the importance of statistically integrating heterogeneity in experimental evolution to identify factors constraining outcome repeatability and study replicability.

evolutionary biology↗

bioRxiv2025

Gonococcal aggregation causes upregulation of genes involved in antibiotic tolerance

Aggregation and biofilm formation can increase the tolerance of bacteria to external stressors, including antibiotic treatment. While resistant bacteria grow at an elevated drug dose, tolerant bacteria survive longer-term treatment. The mechanisms by which aggregation confers tolerance are insufficiently characterized for most organisms, including the human pathogen Neisseria gonorrhoeae. We hypothesize that bacterial aggregation causes upregulation of genes involved in tolerance and that deletion of these genes increases killing rates during antibiotic treatment. To test this hypothesis and identify genes involved in gonococcal tolerance, we compared the transcriptome of aggregating and planktonic N. gonorrhoeae strains. In general, the transcriptome analysis shows that aggregation causes a strong upregulation of prophage-related genes and a shift towards anaerobic respiration. We generated deletion strains for the twenty most upregulated genes and measured their killing kinetics during treatment with the clinically relevant antibiotics ceftriaxone or ciprofloxacin. We identified five genes and one multigene segment that are involved in gonococcal antibiotic tolerance. These include prophage genes whose deletion affects tolerance differently in aggregating and planktonic strains. Furthermore, deletion of genes encoding a putative multi-drug efflux pump, an alcohol dehydrogenase, and a DNA repair protein reduces tolerance. In summary, we have identified multiple genes that affect antibiotic tolerance and are upregulated in response to aggregation. Author summaryOften bacterial infections recur after antibiotic treatment because not all of the bacteria were killed. The ability to survive treatment by bactericidal drugs is termed tolerance. It is well established that aggregation can increase tolerance by reducing growth and metabolism. However, the genes involved in tolerance are not well characterized, especially in the human pathogen Neisseria gonorrhoeae. Here, we aim to identify such genes by following the hypothesis that aggregation upregulates genes that cross-protect N. gonorrhoeae from antibiotic treatment. We show that prophage-associated genes are strongly upregulated in aggregates and that deletion of various phage genes affects tolerance to the currently administered drug, ceftriaxone. We identify three additional genes belonging to different functional classes whose deletion reduces tolerance to ciprofloxacin. Our study is an important step towards understanding the molecular mechanisms of gonococcal antibiotic tolerance. In particular, we propose that prophages could serve as a target for the treatment of tolerant gonococcal infections.

microbiology↗

bioRxiv2023

Genome-wide transformation reveals extensive exchange across closely related Bacillus species

Bacterial transformation is an important mode of horizontal gene transfer that helps spread genetic material across species boundaries. Yet, the factors that pose barriers to genome-wide cross-species gene transfer are poorly characterized. Here, we develop a replacement accumulation assay to study the effects of genomic distance on transfer dynamics. Using Bacillus subtilis as recipient and various species of the genus Bacillus as donors, we find that the rate of orthologous replacement decreases exponentially with the divergence of their core genomes. We reveal that at least 96 % of the B. subtilis core genes are accessible to replacement by alleles from Bacillus spizizenii. For the more distantly related Bacillus atrophaeus, gene replacement events cluster at genomic locations with high sequence identity and preferentially replace ribosomal genes. Orthologous replacement also creates mosaic patterns between donor and recipient genomes, rearranges the genome architecture, and governs gain and loss of accessory genes. We conclude that cross-species gene transfer is dominated by orthologous replacement of core genes which occurs nearly unrestricted between closely related species. At a lower rate, the interplay between the core and accessory genomes gives rise to more complex genome dynamics.

genomics↗

bioRxiv2020

Adaptive evolution of hybrid bacteria by horizontal gene transfer

Horizontal gene transfer is an important factor in bacterial evolution that can act across species boundaries. Yet, we know little about rate and genomic targets of cross-lineage gene transfer, and about its effects on the recipient organisms physiology and fitness. Here, we address these questions in a parallel evolution experiment with two Bacillus subtilis lineages of 7% sequence divergence. We observe rapid evolution of hybrid organisms: gene transfer swaps ~12% of the core genome in just 200 generations, and 60% of core genes are replaced in at least one population. By genomics, transcriptomics, fitness assays, and statistical modeling, we show that transfer generates adaptive evolution and functional alterations in hybrids. Specifically, our experiments reveal a strong, repeatable fitness increase of evolved populations in the stationary growth phase. By genomic analysis of the transfer statistics across replicate populations, we infer that selection on HGT has a broad genetic basis: 40% of the observed transfers are adaptive. At the level of functional gene networks, we find signatures of negative and positive selection, consistent with hybrid incompatibilities and adaptive evolution of network functions. Our results suggest that gene transfer navigates a complex cross-lineage fitness landscape, bridging epistatic barriers along multiple high-fitness paths. Significance statementIn a parallel evolution experiment, we probe lateral gene transfer between two Bacillus subtilis lineages close to the species boundary. We show that laboratory evolution by horizontal gene transfer can rapidly generate hybrid organisms with broad genomic and functional alterations. By combining genomics, transcriptomics, fitness assays and statistical modeling, we map the selective effects underlying gene transfer. We show that transfer takes place under genome-wide positive and negative selection, generating a net fitness increase in hybrids. The evolutionary dynamics efficiently navigates this fitness landscape, finding viable paths with increasing fraction of transferred genes.

evolutionary biology↗