Biology subjects

Freund, F.

Publications and source records attributed to Freund, F..

17 recordsLinked to original sources

bioRxiv2026

Molecular Data From Herbarium Specimens Reveal A Potential Extirpation of Azolla microphylla From California

Previous studies have shown that there may be more species of Azolla in California than currently recognized, including a recent introduction of the non-native Azolla caroliniana. To better assess the status and species diversity of Azolla in California, we sequenced four historical herbarium specimens, some over 100 years old, and increased our sampling of extant populations across seven counties in California. We found that many specimens from California thought to be Azolla microphylla are actually Azolla filiculoides or members of one of two non-native "Azolla caroliniana" clades. We also found that some specimens collected from California from the 1960s through the 1980s fall within an Azolla microphylla-mexicana clade. However, there is no evidence of this species from any recent collections even from counties where it was previously found, which points to a potential extirpation of this species from California.

ecology↗

bioRxiv2026

TMRCA is observable from the branch lengths of a coalescent

The height of ancestral trees, in other words the time to the most recent common ancestor in a genealogical tree, is an informative statistic in population genomics and used in contexts of genealogical dating, demographic history inference, and assessing signals of selection. Exploiting a general pathwise identity between the height of a tree and its branch lengths, we revisit Zeng et al.s mutation rate estimator to develop a model-free estimator for the product of the expected height of genealogical trees with the scaled mutation rate, both for single loci and genomic regions. This estimator is a linear function of the site frequency spectrum of a sample, i.e., of the distribution of allele counts at all segregating sites across the locus or genomic region and thus both observable and computationally cheap. We show that, under the infinite sites model of mutation, our estimator is unbiased and, for two genome-wide models of ancestries (sequential Markovian coalescents and common-pedigree ancestries), consistent. Furthermore, we show via simulation that our estimator performs smaller errors than averaging over reconstructed ancestral tree heights (extracted from reconstructed ancestral recombination graphs) when considering genome properties similar to human genomes across large genomic regions. We then revisit a publicly available genomic dataset of dogs and wolves and compare our method with extracting TMRCAs from ancestral recombination graph reconstructions.

genetics↗

bioRxiv2026

Genomic variation and ancestry of Helicobacter pylori in the admixed population of Cabo Verde reveal host adaptation, limited host-pathogen ancestry concordance, and signatures of trans-Atlantic slave trade migrations

The genomic structure of the stomach-colonising, gastric cancer-associated bacterium Helicobacter pylori mirrors human evolutionary history, making it difficult to disentangle shared ancestry from true host-pathogen interactions driving disease risk. Recently admixed populations offer opportunities for new coevolutionary trajectories between H. pylori and its host that may disrupt parallel evolution. Here, we analyse host H. pylori IgG, blood serum biomarkers, and paired host-bacterial genomic data from the general population (independent of dyspepsia symptoms) of Cabo Verde. Seropositivity is high (82.8%), as in neighbouring African populations. Serum biomarkers indicate that this unique cohort mainly comprises hosts with limited gastric inflammation. Genomic analyses show that Cabo Verdean H. pylori derive European (hspSWeurope) and West African (hspAfrica1WAfrica) ancestry. The delineation of a reference dataset that includes new strains from Ghana and Portugal, uncovered a distinct West-Central African cluster (hspAfrica1WCAfrica). This dataset allowed inference of within-Africa and within-Europe ancestries in Cabo Verdean and American strains that reflect historical migrations linked to European colonisation and the trans-Atlantic Slave Trade. European strains in Cabo Verde show additional population structure, including two low-diversity clusters. Approximate Bayesian Computation (ABC) inference indicates that the most common cluster represents a clonal expansion, likely driven by host adaptation leading to increased transmission within Cabo Verde. Notably, these strains lack known virulence genes and show significant divergence from gastric cancer strains. Finally, host and bacterial ancestry are uncoupled, indicating disruption of ancestral parallel evolution. Cabo Verde, therefore, provides a unique natural model for studying host-pathogen interactions underlying susceptibility to H. pylori.

evolutionary biology↗

bioRxiv2026

How many phage species remain undiscovered? Species sampling approaches to inform phage discovery

The emergence of antimicrobial resistant bacteria has been identified as one of the most serious public health and development threats for the near future. The use of bacteriophages (phages) is a promising solution for the sustainable control of these pathogens. Phages are natural viral predators of bacterial pathogens. However, due to the variability and adaptability of bacteria, developing effective and sustainable phage treatments requires drawing from a wide variety of different phage species. This study applies specialised mathematical and computational estimation approaches to the problem of sampling and discovering species of phages in microbiological communities. Our goal is to predict how many new phage species will be discovered in future samples based on species recorded in a phage sequence database for eight common bacterial hosts. While internal validation shows that current estimators yield low prediction errors for how many new species can be found when sampling more phages, these critically assume that the underlying mechanisms of phage sampling and database inclusion remain similar across time - an assumption put into question by our analysis for all but the host genus Mycobacterium. From this, we discuss how our results can still inform future sampling strategies - both through directly predicting the number of additional species, or by detecting changes in sampling and database inclusion. Our results have the potential to inform and optimise the hunt for and isolation of novel of phages from the the natural environment. HighlightsO_LISpecies abundance distribution of phages infecting seven of eight analysed host bacterial genera collected in phage databases changed significantly over time. C_LIO_LIMaintaining current sampling strategies for phages of host Mycobacteriut may lead to diminishing returns in the number of new phages found in additional samples. C_LIO_LIBoth non-parametric and parametric estimators of the numbers of unseen species show comparable, moderate errors when predicting a random subset from the remainder of hostspecific phage sets from the INPHARED database C_LI

genomics↗

bioRxiv2025

Landscape genomics and demography of California Azolla

Azolla was collected and sequenced across California as a part of the California Conservation Genomics Project. We identify three major populations of Azolla in the state. Out of these groups, we are able to confidently identify one as Azolla filiculoides. The other two taxa are seemingly newly reported to California and are not the same as the taxa currently treated by the Jepson Manual; specifically, they are not members of the A. microphylla/mexicana clade. We infer patterns of Azolla genetic diversity across the state and the demographic histories of these populations. We find evidence that both isolation by distance and isolation by environment contribute to spatial genetic variation. Both of the two newly reported populations have demographic histories consistent with recent invasions of the state. However, we also discuss alternative possibilities and propose a roadmap for resolving the taxonomy of California Azolla.

ecology↗

bioRxiv2024

Muller's Ratchet and Gene Duplication

Copy number of genes in gene families can be highly variable among individuals and may continue to change across generations. Here, we study a model of duplication-selection interaction, which is related to Haighs mutation-selection model of Mullers ratchet. New gene copies are generated by duplication but fitness of individuals decreases as copy number increases. Our model comes in two flavours: duplicates are copied either from a single template or from any existing copy. A duplication-selection equilibrium exists in both cases for infinite size populations and is given by a shifted Poisson or a negative binomial distribution. Unless counteracted by synergistic epistasis, finite populations suffer from loss of low copy-number haplotypes by drift, forcing them into a regime called run-away evolution in which new copies accumulate without bound nor equilibrium. We discuss a few empirical examples and interpret them in the light of our models. Generally, large gene families appear too over-dispersed to fit the single template model suggesting a dynamic, and potentially accelerating, duplication process.

evolutionary biology↗

bioRxiv2024

The genome assembly of the duckweed fern, Azolla caroliniana

Azolla is a genus of freshwater ferns that is economically important as a nitrogen-fixing biofertilizer, biofuel, bioremediator, and for potential carbon sequestration, but also contains weedy invasive species. In California, only two species are currently recognized but there may be up to six putative species, with the discrepancy being due to the difficulty in identifying taxa, hybridization, and the introduction of non-native species. Here, we report a new haplotype-resolved, chromosome-level assembly of Azolla caroliniana as part of the California Conservation Genomics Project (CCGP), using a combination of PacBio HiFi and Omni-C sequencing technologies. The assembly is 521 Mb in length, with a contig N50 of 1.6 Mb, and is scaffolded into 22 pseudo-chromosomes. The BUSCO completeness score is 87.5%, making it the most complete and most contiguous Azolla assembly to date. In combination with the previously published A. filiculoides genome, this A. caroliniana genome will be a powerful tool for understanding the population genetics and taxonomy of one of the most cryptic, economically important, and poorly circumscribed fern taxa, and for facilitating land plant genomics more broadly.

genomics↗

bioRxiv2024

Population genomics and molecular epidemiology of wheat powdery mildew in Europe

Agricultural diseases are a major threat to sustainable food production. Yet, for many pathogens we know exceptionally little about their epidemiological and population dynamics, and this knowledge gap is slowing the development of efficient control strategies. Here we study the population genomics and molecular epidemiology of wheat powdery mildew, a disease caused by the biotrophic fungus Blumeria graminis forma specialis tritici (Bgt). We sampled Bgt for two consecutive years, 2022 and 2023, from 22 countries in Europe and surrounding regions, and compiled a genomic dataset of 415 Bgt isolates. We found one single epidemic unit in the north of Europe, consisting of a highly homogeneous population. Conversely, the south of Europe hosts smaller local populations which are less interconnected. In addition, we show that the population structure can be largely predicted by the prevalent wind patterns. We identified several loci that were under selection in the recent past, including fungicide targets and avirulence genes. Some of these loci are common between populations, while others are not, suggesting different local selective pressures. We reconstructed the evolutionary history of one of these loci, AvrPm17, coding for an effector recognized by the wheat receptor Pm17. We found evidence for a soft sweep on standing genetic variation. Multiple AvrPm17 haplotypes, which can partially escape recognition by Pm17, spread rapidly throughout the continent upon its introduction in the early 2000s. We also identified a new virulent variant, which emerged more recently and can evade Pm17 resistance altogether. Overall, we highlight the potential of genomic surveillance in resolving the evolutionary and epidemiological dynamics of agricultural pathogens, as well as in guiding control strategies.

evolutionary biology↗

bioRxiv2024

The nitrogen-fixing fern Azolla has a complex microbiome characterized by multiple modes of transmission

Azolla is a floating fern that has closely evolved with a vertically transmitted obligate cyanobacterium endosymbiont--Anabaena azollae--that performs nitrogen fixation in specialized Azolla leaf pockets. This cyanobac-terium has a greatly reduced genome and appears to be in the "advanced" stages of symbiosis, potentially evolving into a nitrogen-fixing organelle. However, there are also other lesser-known inhabitants of the leaf pocket whose role and mode of transmission are unknown. We sequenced 112 Azolla specimens collected across the state of California and characterized their metagenomes in order to identify the common bacterial endosymbionts of the leaf pocket and assess their patterns of co-diversification. Four taxa were found across all samples, establishing that there are multiple endosymbionts that consistently inhabit the Azolla leaf pocket. We found varying degrees of co-diversification across these taxa as well as varying degrees of isolation by distance and of pseudogenation, which implies that the endosymbiotic community is transmitted by a mix of horizontal and vertical mechanisms, and that some members of the microbiome are more facultative symbionts than others. These results show that the Azolla symbiotic community is complex, featuring members at potentially different stages of symbiosis evolution, further supporting the utility of the Azolla microcosm as a system for studying the evolution of symbioses.

ecology↗

bioRxiv2023

Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations

Evaluation of the apportionment of genetic diversity of bacterial commensals within and between populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oronasopharingeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher historical population effective size (Ne) in S. mitis, whose genomic variation been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral population and has been subjected to adaptive selection. Strikingly, both species show limited differentiation among populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.

evolutionary biology↗

bioRxiv2022

Simultaneous Inference of Past Demography and Selection from the Ancestral Recombination Graph under the Beta Coalescent

The reproductive mechanism of a species is a key driver of genome evolution. The standard Wright-Fisher model for the reproduction of individuals in a population assumes that each individual produces a number of offspring negligible compared to the total population size. Yet many species of plants, invertebrates, prokaryotes or fish exhibit neutrally skewed offspring distribution or strong selection events yielding few individuals to produce a number of offspring of up to the same magnitude as the population size. As a result, the genealogy of a sample is characterized by multiple individuals (more than two) coalescing simultaneously to the same common ancestor. The current methods developed to detect such multiple merger events do not account for complex demographic scenarios or recombination, and require large sample sizes. We tackle these limitations by developing two novel and different approaches to infer multiple merger events from sequence data or the ancestral recombination graph (ARG): a sequentially Markovian coalescent (SM{beta}C) and a graph neural network (GNNcoal). We first give proof of the accuracy of our methods to estimate the multiple merger parameter and past demographic history using simulated data under the {beta}-coalescent model. Secondly, we show that our approaches can also recover the effect of positive selective sweeps along the genome. Finally, we are able to distinguish skewed offspring distribution from selection while simultaneously inferring the past variation of population size. Our findings stress the aptitude of neural networks to leverage information from the ARG for inference but also the urgent need for more accurate ARG inference approaches.

genetics↗

bioRxiv2022

Interpreting the pervasive observation of U-shaped Site Frequency Spectra

The standard neutral model of molecular evolution has traditionally been used as the null model for population genomics. We gathered a collection of 45 genome-wide site frequency spectra from a diverse set of species, most of which display an excess of low and high frequency variants compared to the expectation of the standard neutral model, resulting in U-shaped spectra. We show that multiple merger coalescent models often provide a better fit to these observations than the standard Kingman coalescent. Hence, in many circumstances these under-utilized models may serve as the more appropriate reference for genomic analyses. We further discuss the underlying evolutionary processes that may result in the widespread U-shape of frequency spectra.

evolutionary biology↗

bioRxiv2020

Population history of the Northern corn leaf blight fungal pathogen Setosphaeria turcica in Europe

Modern agricultural practices and the climate change foster the rapid spread of plant pathogens like the maize fungal pathogen Setosphaeria turcica, which causes Northern corn leaf blight and expanded into Central Europe since the 1980s. To investigate the rapid expansion of S. turcica we sequenced 121 isolates from Europe and Kenya. Population genomic inference revealed a single genetically diverse cluster in Kenya and three clonal lineages with low diversity and one cluster of multiple clonal sublineages in Europe. Phylogenetic dating suggests that all European lineages originated by sexual reproduction outside Europe and subsequently were subsequently introgressed multiple times. In contrast to Kenyan isolates, European isolates did not show sexual recombination despite the presence of both MAT1-1 and MAT1-2 mating types. Coalescent analysis of the geographically most widespread European lineage supported a neutral, strongly exponential population growth model over models with natural selection caused by host defence resistance or environmental adaptation. Within clonal lineages, we observed phenotypic variation in virulence to different monogenic resistances that may originate from repeated mutations in virulence genes. Association mapping between genetic clusters did not identify genomic regions associated with pathogen races but uncovered strongly differentiated genomic regions between clonal lineages that harbor putative effector genes. In conclusion, the expansion and population growth of S. turcica in Europe was mainly driven by the expansion of maize cultivation area and not by rapid adaptation. Significance statementThe geographic expansion and plant pathogens caused by modern agricultural practices and climate change is a major problem in modern agriculture. We investigated the rapid spread of the maize fungal pathogen Setosphaeria turcica by whole genome sequencing of isolates from Kenya and Europe and demonstrated that the rapid expansion in Central Europe since the 1980s mainly reflects the rapid growth of the maize cultivation area in this region and not a rapid adaptation to resistant maize varieties. Our analyses show that by monitoring whole genome sequence diversity of plant pathogens and their invasion history, agricultural management and breeding strategies can be developed to control the evolution and future spread of plant pathogens.

evolutionary biology↗

bioRxiv2019

Multiple merger genealogies in outbreaks of Mycobacterium tuberculosis

The Kingman coalescent and its developments are often considered among the most important advances in population genetics of the last decades. Demographic inference based on coalescent theory has been used to reconstruct the population dynamics and evolutionary history of several species, including Mycobacterium tuberculosis (MTB), an important human pathogen causing tuberculosis. One key assumption of the Kingman coalescent is that the number of descendants of different individuals does not vary strongly, and violating this assumption could lead to severe biases caused by model misspecification. Individual lineages of MTB are expected to vary strongly in reproductive success because 1) MTB is potentially under constant selection due to the pressure of the host immune system and of antibiotic treatment, 2) MTB undergoes repeated population bottlenecks when it transmits from one host to the next, and 3) some hosts show much higher transmission rates compared to the average ("super-spreaders"). Here we used an Approximate Bayesian Computation approach to test whether multiple merger coalescents (MMC), a class of models that allow for large variation in reproductive success among lineages, are more appropriate models to study MTB populations. We considered eleven publicly available whole genome sequence data sets sampled from local MTB populations and outbreaks, and found that MMC had a better fit compared to the Kingman coalescent for ten of the eleven data sets. These results indicate that the null model for analyzing MTB outbreaks should be reassessed, and that past findings based on the Kingman coalescent need to be revisited.

evolutionary biology↗

bioRxiv2019

Distinguishing coalescent models - which statistics matter most?

Modelling genetic diversity needs an underlying genealogy model. To choose a fitting model based on genetic data, one can perform model selection between classes of genealogical trees, e.g. Kingmans coalescent with exponential growth or multiple merger coalescents. Such selection can be based on many different statistics measuring genetic diversity. A random forest based Approximate Bayesian Computation is used to disentangle the effects of different statistics on distinguishing between various classes of genealogy models. For the specific question of inferring whether genealogies feature multiple mergers, a new statistic, the minimal observable clade size, is introduced. When combined with classical site frequency based statistics, it reduces classification errors considerably.

evolutionary biology↗

bioRxiv2017

Inferring the evolutionary reduction of corm lobation in Isoëtes using Bayesian model-averaged ancestral state reconstruction

Inferring the evolution of characters in Isoetes has been problematic, as these plants are morphologically conservative and yet highly variable and homoplasious within that conserved base morphology. However, molecular phylogenies have given us a valuable tool to test hypothesis of character evolution within the genus. One such hypothesis is that extant Isoetes have undergone a morphological reduction from larger arborescent lycophyte ancestors. In this work we examine the reduction in lobe numbers on the underground trunk, or corm, over evolutionary time. Using reversible-jump MCMC and Bayesian inference, our results support the hypothesis of a directional reduction in lobe number in Isoetes, with the best-supported model of character evolution being one of irreversible reduction. Furthermore, the most probable ancestral corm lobe number of extant Isoetes is three, and a reduction to two lobes has occurred at least six times. From our results, we can infer that corm lobation, like many other traits in Isoetes, shows a degree of homoplasy, yet also shows ongoing evolutionary reduction.

evolutionary biology↗

bioRxiv2017

Genealogical properties of subsamples in highly fecund populations

We consider some genealogical properties of nested samples. The complete sample is assumed to have been drawn from a natural population characterised by high fecundity and sweepstakes reproduction (abbreviated HFSR). The random gene genealogies of the samples are -- due to our assumption of HFSR -- modelled by coalescent processes which admit multiple mergers of ancestral lineages looking back in time. Among the genealogical properties we consider are the probability that the most recent common ancestor is shared between the complete sample and the subsample nested within the complete sample; we also compare the lengths of internal branches of nested genealogies between different coalescent processes. The results indicate how informative a subsample is about the properties of the larger complete sample, how much information is gained by increasing the sample size, and how the informativeness of the subsample varies between different coalescent processes.

evolutionary biology↗