Biology subjects

Wiehe, T.

Publications and source records attributed to Wiehe, T..

17 recordsLinked to original sources

bioRxiv2025

Interlocus gene conversion causes mosaic divergence in tandem paralogues - simulating HMA4 evolution in Arabidopsis halleri

Following gene duplication, the evolutionary trajectories of gene copies can be shaped by various processes including mutation, selection, recombination and interlocus gene conversion (IGC). To explore their dynamics and consequences, we developed a mathematical model that simulates the early evolution of recently duplicated, tandemly arrayed gene families with positive selection on the new gene copy. We compared the results of our model to sequence variation of the three tandemly arrayed HEAVY METAL ATPase 4 (HMA4) gene copies of Arabidopsis halleri, which are known to undergo IGC. However, rate and efficacy of IGC vary within genes, resulting in a mosaic pattern of divergence. Informed by empirical data, our model captures the impact of IGC and unequal crossing-over on the diversity within each gene copy and the divergence among them. By tailoring the model to the HMA4 gene copies, we demonstrate the models flexibility and its potential to provide insights into the evolutionary dynamics driving the evolution of tandemly arrayed paralogues. This study enhances our understanding of the balance between homogenization and divergence of gene family evolution.

evolutionary biology↗

bioRxiv2025

Inferring the history of gene copy number evolution

Gene duplication plays a crucial role in the adaptive evolution and diversification of organisms by creating extra copies of genes that can evolve new functions while preserving the original. Duplicated genes can become fixed in populations or appear as copy number variants. However, inferring and dating these duplication events from present-day data is challenging, as gene copy count distributions could result from either a few ancient duplication events or many recent ones. Sequence based phylogenetic reconstruction, an often seen practice, does not include the history of individuals and hence may result in inconsistencies, which may lead to misinterpretations. Here, we introduce a novel model for inferring gene copy number evolution, which describes gene duplication and their evolution over time through a random walk on a coalescent duplication network. This approach is solely based on copy number counts and hence independent of the inconsistencies of sequence based inferences. Backward in time we implement structured coalescent simulations, where we re-interprete structure as genealogical distance based on copy number counts. We apply this model to the NB-ARC domain counts of NLR genes in A. thaliana to infer the number and times of duplication events that have led to the present day copy number distribution.

evolutionary biology↗

bioRxiv2025

Copy Number Variation: A Substrate for Plant Adaptation and Stress Response in Arabidopsis

Copy number variation (CNV) is a major source of genomic diversity that shapes gene family evolution and may contribute to ecological differentiation, yet its genome-wide ecological relevance remains poorly understood. Here, we analyzed CNV across four Brassicaceae species (Arabidopsis thaliana, A. lyrata, A. halleri, and Arabis alpina) to identify gene families undergoing rapid expansion or contraction. Using a birth-death model, we identified 231 rapidly evolving gene families spanning diverse functional categories. We then characterized CNV within populations of A. thaliana and A. lyrata using population-scale long-read assemblies. CNV exhibited strong heterogeneity across gene families and species, with contrasting evolutionary outcomes: A. thaliana showed greater retention of duplicated copies, whereas A. lyrata exhibited higher pseudogenization and turnover. CNV profiles were strongly structured geographically, reflecting known demographic and phylogeographic patterns in both species. Environmental association analyses revealed species-specific architectures: CNV in A. thaliana showed a diffuse, polygenic association with climate, whereas in A. lyrata associations were more strongly coupled to population structure. Despite the functional diversity of rapidly evolving families, environmentally associated CNVs were significantly enriched in defense- and stress-related functions. These results demonstrate that CNV-environment relationships emerge at the level of gene family networks and are shaped by genomic architecture and lineage history, highlighting CNV as a context-dependent driver of genome evolution and ecological differentiation. SummaryGene copy number variation--where individuals carry different numbers of copies of the same gene--is a potentially important but poorly understood source of genetic diversity. The authors studied how copy numbers evolve across four mustard family plant species and whether this variation helps plants adapt to different environments. They found that gene families involved in disease resistance and stress responses were especially prone to rapid copy number changes. These changes tracked geography and local climate, but in ways that differed between species depending on their evolutionary history. The findings highlight gene copy number variation as a key, underappreciated contributor to how plants adapt to their environments.

evolutionary biology↗

bioRxiv2025

Decay of the CTCF paralog BORIS in neognathous birds

BORIS (brother of the regulator of imprinted sites), the paralog of the genome organizer CTCF, originated at least 318 million years ago (Mya), in the ancestor of amniotes (mammals, reptiles, and birds). Based on results from chicken (Gallus gallus), the gene was thought to be absent from birds. Using comparative genomics of 59 bird species, we show that birds possess BORIS, but frequently experience severe degradation of the gene, as observed in Gallus gallus. The degradation events are restricted to neognathous birds, specific for the BORIS coding sequence, and occur multiple times independently on different branches. They comprise a wide range of molecular decay, from individual point mutations to the inactivation and/or loss of particular zinc fingers, to the almost complete disintegration of the gene. The decay is accompanied by relaxed evolutionary constraints on BORIS codons across neognathous birds and coincides with the accumulation of species-specific repetitive elements in degenerate loci. BORIS represents a case of a presently ongoing, convergent, and specific gene loss within a lineage. As possible explanation, we propose a link between the loss of BORIS and a shift in sperm and/or genital morphology during the evolution of Neognathae. Significance StatementThe gene BORIS was believed to be absent from birds. However, genome analysis of 59 bird species reveals its presence, though it often underwent severe degradation in neognathous birds. These independent degradation events affect the BORIS coding sequence and range from point mutations to near complete gene disintegration. This decay correlates with relaxed evolutionary constraints and species-specific accumulation of repetitive elements. A potential link between BORIS loss and changes in sperm or genital morphology during neognathous bird evolution is suggested.

evolutionary biology↗

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↗

bioRxiv2023

Genome-wide SNP data reveal recent population structure of Huidobria fruticosa (Loasaceae), a paleo-endemic lineage from the Atacama Desert

The Atacama Desert is a biodiversity hotspot of neo-endemic radiation, where long-term aridity and complex physiographic processes create a unique environmental setting. Current species assemblages are mainly concentrated in highly patchy loma formations, and plant populations occurring in these are often geographically isolated from each other. Despite a general consensus on long-term aridity in the Atacama, climatological and geological evidence points to repeated climate change, making the Atacama Desert an ideal system for studying population genetic processes in highly unstable habitats. We are analyzing the genetic structure within and between populations of Huidobria fruticosa, a paleo-endemic lineage of the Atacama Desert, to shed new light on its biogeographic history and broaden our understanding of the evolution of life in extreme aridity, as well as plant evolution in response to a changing environment. To do this, we analyzed SNP data from genotyping-by-sequencing of 354 individuals from 21 populations. Our results suggest that, despite being an ancient lineage, the current population structure of Huidobria fruticosa only reflects changing abiotic conditions over the last 2 million years. We therefore conclude that the present distribution, together with the evolutionary processes documented here, is the result of climatic fluctuations and prolonged periods of hyperaridity during the Pleistocene. Building on this understanding, our findings contribute to a global narrative that highlights the complex interplay between climate change and evolutionary dynamics, and emphasize the importance of deserts as living laboratories for deciphering how species have historically adapted to some of the most extreme habitats on Earth.

evolutionary biology↗

bioRxiv2023

Genetic diversity of the Atacama Desert shrub Huidobria chilensis in the context of geography and climate

Survival in hyperarid deserts is a major challenge for plant life, requiring the development of evolutionary strategies. The Atacama Desert presents harsh conditions such as limited rainfall, crusted soils, high soil salinity, high altitude, and intense solar radiation. These conditions, together with paleoclimatic variability since the past millions of years, have influenced the genetic structure and connectivity of plant populations, resulting in a diverse flora with high endemism. However, the diversification of most lineages appears to be relatively recent, in contrast to proposed age of the Atacama Desert and the onset, evolution and expansion of hyperarid conditions since the Late Oligocene and Early Miocene. A prominent exception is the Atacama paleoendemic Huidobria chilensis (Loasaceae), which is thought to be adapted to such conditions since the Eocene. Still, the environmental limits and thresholds for life in the Atacama remain poorly understood. To investigate the genetic structure in relation to the history of the Atacama Desert, we studied 186 individuals from 11 populations using genotyping-by-sequencing (GBS). Genome-wide single nucleotide polymorphisms (SNPs) were analyzed for population structure and genetic diversity. We identified three genetic clusters corresponding to geographic regions: the coastal region south of Tocopilla, the Coastal Cordillera around Chanaral, and the Copiapo watershed in the south. These clusters as well as genetic diversity were analyzed alongside rainfall, altitude, and landscape data. Although the genetic data generally supports isolation by distance as a major factor for genetic variation between populations, the study also reveals the influence of the topography on the distribution of H. chilensis and highlights the role of hydrologically connected watersheds and rivers in plant migration and colonization. This shapes the species evolutionary trajectory and genetic diversity. Understanding these patterns provides insights into the adaptation and survival strategies of plants in extreme desert environments such as the Atacama.

genetics↗

bioRxiv2023

Copy number variation and population-specific immune genes in the model vertebrate zebrafish

Many species have hundreds of immune genes from the NLR family (Nucleotide-binding domain Leucine-rich Repeat containing). In plants they have a considerable amount of within-species variation, but not much is known about their variability in fishes. Here we captured and analysed the diversity of NLRs in zebrafish (Danio rerio) by sequencing 93 individuals from four wild and two laboratory strains. We found 1,560 unique NLR genes, and theoretical modelling revealed each wild population to have around 2,000. Only 100-550 were detected in each individual fish, and the observed variance of copy numbers differed among populations. Laboratory strains were found to have three times less NLRs than wild populations, and their genetic diversity was lower in general. Many NLRs showed no single nucleotide variation, but those that did showed evidence of purifying selection. Our study lays the groundwork for unraveling mechanisms driving the evolution of this large gene family in vertebrates. Significance statementWe show here that the gene repertoires of vertebrates can be extremely variable, with different individuals having different genes. By sequencing one large family of immune receptors from 93 wild and laboratory zebrafish we found hundreds of novel gene copies, each only present in specific strains or specific individuals. Our observations can be explained by a combination of complex patterns of inheritance and a high rate of gene birth and death.

genetics↗

bioRxiv2023

Distinguishing the roles of adaptation and demography in gene copy number changes in human populations

Genes with multiple copies are likely to be maintained by stabilizing selection that puts a bound to unlimited expansion of copy number. We designed a model where copy number variation is generated by unequal recombination, which fits well to a number of genes, surveyed in three human populations. Based on this theoretical model and on computer simulations, we were interested in answering the question whether gene copy number distribution in the derived European and Asian populations can be explained by a purely demographic scenario or whether shifts in the distribution are signatures of adaptation. Although copy number distribution in most of the analyzed gene clusters can be explained by a bottleneck as in the out of Africa expansion of homo sapiens 60-10kyrs ago, we identified several candidate genes, for instance AMY1A and PGA3, whose copy numbers are likely to be selected differently among African, Asian and European populations.

evolutionary biology↗

bioRxiv2022

Parthenogenetic Panagrolaimus species evolve at lower mutation rates, but show increased nucleotide diversity

Asexual reproduction is assumed to lead to the accumulation of deleterious mutations, and reduced heterozygosity due to the absence of recombination. Panagrolaimid nematode species display different modes of reproduction. Sexual reproduction with distinct males and females, asexual reproduction through parthenogenesis in the genus Panagrolaimus, and hermaphroditism in Propanagrolaimus. Here, we compared genomic features of free-living nematode populations in populations and species isolated from geographically distant regions to study diversity, and genome-wide differentiation under different modes of reproduction. We firstly estimated genome-wide spontaneous mutation rates in a triploid parthenogenetic Panagrolaimus population, and a diploid hermaphroditic Propanagrolaimus species via long-term mutation-accumulation-lines. Secondly, we calculated population genetic parameters including nucleotide diversity, and fixation index (FST) between populations of asexually and sexually reproducing nematodes. Thirdly, we used phylogenetic network methods on sexually and asexually reproducing Panagrolaimus populations to understand evolutionary relationships between them. The estimated mutation rate was slightly lower for the asexual population, as expected for taxa with this reproductive mode. Natural polyploid asexual populations revealed higher nucleotide diversity. Despite their common ancestor, a gene network revealed a high level of genetic differentiation among asexual populations. The elevated heterozygosity found in the triploid parthenogens could be explained by the third genome copy. Given their tendentially lower mutation rates it can be hypothesized that this is part of the mechanism to evade Mullers ratchet. Our findings in parthenogenetic triploid nematode populations seem to challenge common expectations of evolution under asexuality.

evolutionary biology↗

bioRxiv2022

Recombination, selection and the evolution of tandem gene arrays

Multi-gene families - immunity genes or sensory receptors, for instance - are often subject to diversifying selection. Allelic diversity may be favoured not only through balancing or frequency dependent selection at individual loci, but also by associating different alleles in multi copy gene families. Using a combination of analytical calculations and simulations, we explored a population genetic model of epistatic selection and unequal recombination, where a trade-off exists between the benefit of allelic diversity and the cost of copy abundance. Starting from the neutral case, where we showed that gene copy number is Gamma-distributed at equilibrium, we derived also mean and shape of the limiting distribution under selection. Considering a more general model which includes variable population size and population substructure, we explored by simulations mean fitness and some summary statistics of the copy number distribution. We determined the relative effects of selection, recombination and demographic parameters in maintaining allelic diversity and shaping mean fitness of a population. One way to control the variance of copy number is by lowering the rate of unequal recombination. Indeed, when encoding recombination by a rate modifier locus, we observe exactly this prediction. Finally, we analyzed the empirical copy number distribution of three genes in human and estimated recombination and selection parameters of our model.

evolutionary biology↗

bioRxiv2019

A discrete approach to the external branches of a Kingman coalescent tree. Theoretical results and practical applications

The Kingman coalescent process is a classical model of gene genealogies in population genetics. It generates Yule-distributed, binary ranked tree topologies--also called histories--with a finite number of n leaves, together with n -1 exponentially distributed time lengths: one for each each layer of the history. Using a discrete approach, we study the lengths of the external branches of Yule distributed histories, where the length of an external branch is defined as the rank of its parent node. We study the multiplicity of external branches of given length in a random history of n leaves. A correspondence between the external branches of the ordered histories of size n and the non-peak entries of the permutations of size n -1 provides easy access to the length distributions of the first and second longest external branch in a random Yule history and coalescent tree of size n. The length of the longest external branch is also studied in dependence of root balance of a random tree. As a practical application, we compare the observed and expected number of mutations on the longest external branches in samples from natural populations.

evolutionary biology↗

bioRxiv2019

The laboratory domestication of zebrafish: from diverse populations to inbred substrains

The zebrafish (Danio rerio) is a model vertebrate widely used to study disease, development and other aspects of vertebrate biology. Most of the research is performed on laboratory strains, one of which has been fully sequenced in order to derive a reference genome. It is known that the laboratory strains differ genetically from each other, but so far no genome-scale survey of variation between the laboratory and wild zebrafish populations exists.\n\nHere we use Restriction-Associated DNA sequencing (RAD-seq) to characterize three different wild zebrafish lineages from a population genetic viewpoint, and to compare them to four common laboratory strains. For this purpose we combine new genome-wide sequence data obtained from natural samples in India, Nepal and Bangladesh with a previously published dataset. We measured nucleotide diversity, heterozygosity, allele frequency spectra and patterns of gene conversion, and find that wild fish are much more diverse than laboratory strains. Further, in wild zebrafish there is a clear signal of GC-biased gene conversion that is missing in laboratory strains. We also find that zebrafish populations in Nepal and Bangladesh are distinct from all the other strains studied, making them an attractive subject for future studies of zebrafish population genetics and molecular ecology. Finally, isolates of the same strains kept in different laboratories show a clear pattern of ongoing differentiation into genetically distinct substrains. Together, our findings broaden the basis for future genetic and evolutionary studies in Danio rerio.

genetics↗

bioRxiv2018

Interdependence of linkage disequilibrium, chromatin architecture and compositional genome organization of mammals

Recent investigation established a link between DNA sequences and chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse the relationship between chromatin architecture and recombination landscapes of human and mouse. The results revealed that: (1) Blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhood; (2) double strand break (DSB) and recombination frequencies increase in GC-rich TADs, whereas recombination cold spots are typical of LADs; (3) binding and loading of proteins which are critical for DSB and meiotic recombination (Spo11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated to compositional and epigenetic features (genomic code) that are similar to those guiding the architecture of chromosomes in the interphase nucleus of pre-leptotene spermatocytes.

genomics↗

bioRxiv2018

Topological linkage disequilibrium calculated from coalescent genealogies

We revisit the classical concept of two-locus linkage disequilibrium (LD) and introduce a novel way of looking at haplotypes. In contrast to defining haplotypes as allele combinations at two marker loci, we concentrate on the clustering of sampled chromosomes induced by their coalescent genealogy. The root of a binary coalescent trees defines two clusters of chromosomes. At two different loci this assignment may be different as a result of recombination. We show that the amount of shared chromosomes among clusters at two different loci, measured by the squared correlation, constitutes a natural measure of LD. We call this topological LD (tLD) since it is induced by the topology of the coalescent tree. We find that its rate of decay decreases more slowly with distance between loci than that of conventional LD. Furthermore, tLD has a smaller coefficient of variation, which should render it more accurate for any kind of mapping purposes than conventional LD. We conclude with a practical application to the LCT region in human populations.

evolutionary biology↗

bioRxiv2017

Signatures of the evolution of parthenogenesis and cryptobiosis in the genomes of panagrolaimid nematodes

Most animal species reproduce sexually, but parthenogenesis, asexual reproduction of various forms, has arisen repeatedly. Parthenogenetic lineages are usually short lived in evolution; though in some environments parthenogenesis may be advantageous, avoiding the cost of sex. Panagrolaimus nematodes have colonised environments ranging from arid deserts to arctic and antarctic biomes. Many are parthenogenetic, and most have cryptobiotic abilities, being able to survive repeated complete desiccation and freezing. It is not clear which genomic and molecular mechanisms led to the successful establishment of parthenogenesis and the evolution of cryptobiosis in animals in general. At the same time, model systems to study these traits in the laboratory are missing.\n\nWe compared the genomes and transcriptomes of parthenogenetic and sexual Panagrolaimus able to survive crybtobiosis, as well as a non-cryptobiotic Propanogrolaimus species, to identify systems that contribute to these striking abilities. The parthenogens are most probably tripoids originating from hybridisation (allopolyploids). We identified genomic singularities like expansion of gene families, and selection on genes that could be linked to the adaptation to cryptobiosis. All Panagrolaimus have acquired genes through horizontal transfer, some of which are likely to contribute to cryptobiosis. Many genes acting in C. elegans reproduction and development were absent in distant nematode species (including the Panagrolaimids), suggesting molecular pathways cannot directly be transferred from the model system.\n\nThe easily cultured Panagrolaimus nematodes offer a system to study developmental diversity in Nematoda, the molecular evolution of parthenogens, the effects of triploidy on genomes stability, and the origin and biology of cryptobiosis.

evolutionary biology↗

bioRxiv2017

The expected neutral frequency spectrum of linked sites

We introduce the conditional Site Frequency Spectrum (SFS) for a genomic region linked to a focal mutation of known frequency. An exact expression for its expected value is provided for the neutral model without recombination. Its relation with the expected SFS for two sites, 2-SFS, is discussed. These spectra derive from the coalescent approach of Fu (1995) for finite samples, which is reviewed. Remarkably simple expressions are obtained for the linked SFS of a large population, which are also solutions of the multiallelic Kolmogorov equations. These formulae are the immediate extensions of the well known single site{theta} /f neutral SFS. Besides the general interest in these spectra, they relate to relevant biological cases, such as structural variants and introgressions. As an application, a recipe to adapt Tajimas D and other SFS-based neutrality tests to a non-recombining region containing a neutral marker is presented.

genetics↗