Biology subjects

Santer, M.

Publications and source records attributed to Santer, M..

6 recordsLinked to original sources

bioRxiv2026

Horizontal transfer promotes allele segregation in multicopy plasmids

Plasmids reside within prokaryotic cells in multiple copies and can spread horizontally between hosts. Their multicopy nature enables intracellular allele diversity (heteroplasmy), and their segregation depends on the modes of plasmid replication and partition. Horizontal plasmid transfer has the potential to alter plasmid allele composition, however its impact on plasmid allele dynamics remains poorly understood. Here, we show that conjugative plasmid transfer accelerates the segregation of plasmid heteroplasmy by promoting the emergence of homoplasmic hosts. Using a quantitative experimental system to track plasmid allele dynamics in Acinetobacter baylyi under non-selective conditions, we followed the fate of a novel antibiotic resistance allele introduced into an ancestral donor population. While alleles in heteroplasmic donors segregated over time, conjugation produced almost only homoplasmic recipients whose allele composition closely mirrored that of the donor pool. Heteroplasmic recipients were rare and arose primarily from multiple plasmid transfer events prior to plasmid establishment. A mathematical model calibrated to the experimental setup predicts that conjugation accelerates plasmid allele segregation, with effects scaling with plasmid copy number and conjugation frequency. Our findings identify horizontal transfer as a previously unrecognized segregation pathway shaping the evolution of mobile genetic elements.

evolutionary biology↗

bioRxiv2025

Persistence of large conjugative plasmids relies on the combination of active partitioning and addiction mechanisms

Extrachromosomal and mobile genetic elements, including transposable elements, plasmids, and accessory chromosomes, are found across all domains of life. The replication and segregation of elements integrated into the host chromosome are ensured by the host life cycle. In contrast, the persistence of autonomously replicating elements relies on their ability to remain within the host population. Here, we compare the evolutionary advantage of different persistence strategies found in prokaryotic plasmids. Through intracellular competitions between plasmid genotypes, we find that the combination of active partitioning during cell division with a toxin-antitoxin (TA) system for post-segregational killing increases plasmid fitness more than either strategy alone. Mathematical modeling of long-term plasmid evolution, calibrated with empirical plasmid loss dynamics, further supports these findings. A survey of enterobacterial genomes indicates that partitioning and TA systems are core features of large conjugative plasmids. Indeed, we confirm the presence of a previously unrecognized type I TA system in IncX3 plasmids, which serve as important vectors of antibiotic resistance in human pathogens. These findings suggest that large conjugative plasmids encode TA systems, including those yet to be identified. The combination of TA and partitioning systems emerges as the most effective strategy for the evolutionary success of low-copy extrachromosomal elements.

microbiology↗

bioRxiv2023

Heteroplasmy is rare in plant mitochondria compared to plastids despite similar mutation rates

Plant cells harbor two membrane-bound organelles containing their own genetic material - plastids and mitochondria. Although the two organelles co-exist and co-evolve within the same plant cells, they differ in genome copy number, intracellular organization, and mode of inheritance. How these attributes determine the time to fixation, or conversely, loss of neutral alleles is currently unresolved. Here we show that mitochondria and plastids share the same mutation rate yet plastid alleles remain in a heteroplasmic state significantly longer compared to mitochondrial alleles. By analysing genetic variants across populations of the marine flowering plant Zostera marina and simulating organelle allele dynamics, we examine the determinants of allele segregation and fixation time. Our results suggest that bottleneck on the cell population, e.g., during branching and seeding, and stratification of the meristematic tissue, are important determinants of mitochondrial allele dynamics. Furthermore, we suggest that the prolonged plastid allele dynamics are due to a yet unknown active plastid partition mechanism. The dissimilarity between plastid and mitochondrial novel allele fixation at different levels of organization may figure into differences in adaptation processes. Our study uncovers fundamental principles of organelle population genetics that are essential for further investigations of long-term evolution and molecular dating of divergence events.

bioinformatics↗

bioRxiv2023

Segregational drift hinders the evolution of antibiotic resistance on polyploid replicons

The emergence of antibiotic resistance under treatment depends on the availability of resistance alleles and their establishment in the population. Novel resistance alleles are encoded either in chromosomal or extrachromosomal genetic elements; both types may be present in multiple copies within the cell. However, the effect of polyploidy on the emergence of antibiotic resistance remains understudied. Here we show that the establishment of resistance alleles in microbial populations depends on the ploidy level. Evolving bacterial populations under selection for antibiotic resistance, we demonstrate that resistance alleles in polyploid elements are lost frequently in comparison to alleles in monoploid elements due to segregational drift. Integrating the experiments with a mathematical model, we find an agreement between the theoretical and empirical allele dynamics, confirming our understanding of the allele segregation process. Using the mathematical model, we further show that the effect of polyploidy on the establishment probability of beneficial alleles is strongest for low replicon copy numbers and plateaus for high replicon copy numbers. Our results suggest that the distribution of fitness effects for mutations that get fixed in a population depends on the replicon ploidy level. Our study indicates that strategies for drug treatment of bacterial infections should take into consideration the pathogen ploidy level.

microbiology↗

bioRxiv2022

Fixation dynamics of beneficial alleles in prokaryotic polyploid chromosomes and plasmids

Theoretical population genetics has been mostly developed for sexually reproducing diploid and for monoploid (haploid) organisms, focusing on eukaryotes. The evolution of bacteria and archaea is often studied by models for the allele dynamics in monoploid populations. However, many prokaryotic organisms harbor multicopy replicons - chromosomes and plasmids - and theory for the allele dynamics in populations of polyploid prokaryotes remains lacking. Here we present a population genetics model for replicons with multiple copies in the cell. Using this model, we characterize the fixation process of a dominant beneficial mutation at two levels: the phenotype and the genotype. Our results show that, depending on the mode of replication and segregation, the fixation time of mutant phenotypes may precede the genotypic fixation time by many generations; we term this time interval the heterozygosity window. We furthermore derive concise analytical expressions for the occurrence and length of the heterozygosity window, showing that it emerges if the copy number is high and selection strong. Replicon ploidy thus allows for the maintenance of genetic variation following phenotypic adaptation and consequently for reversibility in adaptation to fluctuating environmental conditions.

evolutionary biology↗

bioRxiv2019

Evolutionary rescue and drug resistance on multicopy plasmids

Bacteria often carry "extra DNA" in form of plasmids in addition to their chromosome. Many plasmids have a copy number greater than one such that the genes encoded on these plasmids are present in multiple copies per cell. This has evolutionary consequences by increasing the mutational target size, by prompting the (transitory) co-occurrence of mutant and wild-type alleles within the same cell, and by allowing for gene dosage effects. We develop and analyze a mathematical model for bacterial adaptation to harsh environmental change if adaptation is driven by beneficial alleles on multicopy plasmids. Successful adaptation depends on the availability of advantageous alleles and on their establishment probability. The establishment process involves the segregation of mutant and wild-type plasmids to the two daughter cells, allowing for the emergence of mutant-homozygous cells over the course of several generations. To model this process, we use the theory of multi-type branching processes, where a type is defined by the genetic composition of the cell. Both factors - the number of adaptive alleles and their establishment probability - depend on the plasmid copy number, and they often do so antagonistically. We find that in the interplay of various effects, a lower or higher copy number may maximize the probability of evolutionary rescue. The decisive factor is the dominance relationship between mutant and wild-type plasmids and potential gene dosage effects. Results from a simple model of antibiotic degradation indicate that the optimal plasmid copy number may depend on the specific environment encountered by the population.

evolutionary biology↗