Biology subjects

Schartl, M.

Publications and source records attributed to Schartl, M..

At least 19 recordsLinked to original sources

bioRxiv2026

An ancestral pronephric contribution reveals the multilineage origin of the teleost gonad and revises the evolution of vertebrate gonadogenesis

Challenging the paradigm that pronephric field contribution to gonadal formation would be an amniote innovation, we demonstrate this trait is ancestral to bony vertebrates. Using cell lineage tracing, single-cell and spatial transcriptomics, and functional validation, we show that the teleost gonad arises from three distinct embryonic tissues, the pronephros, the coelomic epithelium, and the lateral plate mesoderm, in contrast to amniotes. This multi-tissue origin generates an unexpected lineage-based cellular diversity. Further cross-species comparisons over medaka, mouse, chicken and turtle unravel how lineage-specific deviations shape early gonadal development. Specifically, we map these variations amongst the different gene regulatory networks, outlining their physiological implications for specialized gonadal functions. Our results support a model in which heterochronic shifts are coupled to regulatory rewiring of conserved gene networks, driving lineage-specific developmental trajectories through a canalized developmental system drift.

developmental biology↗

bioRxiv2026

Achiasmatic meiosis underlies propagation of clonal genome and B chromosomes in hexaploid Carassius gibelio females but not males

Sexual reproduction in eukaryotes relies on meiosis, recombination, and fertilization, yet hybridization can lead to transitions to asexuality. Asexual vertebrate hybrids require modified gametogenesis to produce unreduced gametes, but the underlying mechanisms remain poorly understood in various hybrid complexes. Here, we investigated the Carassius gibelio complex, which combines clonal genome propagation to the offspring along with the transmission of B chromosomes. We analyzed meiotic progression and gametogenesis in sexual tetraploid and asexual hexaploid lineages, focusing on sex-specific differences. Cytological analyses of synaptonemal complexes and diplotene chromosomes revealed that both sexes in hexaploid lineages undergo achiasmatic meiosis, characterized by the absence of homologous pairing, recombination, and chiasmata. Chromosomes persist as univalents throughout meiotic prophase. Despite this shared meiotic program, outcomes differ between sexes: females complete oogenesis and produce unreduced eggs, whereas males exhibit disrupted spermatogenesis and reduced fertility. Females bypass the reductional division, enabling clonal gamete formation, while males fail to segregate univalents properly. Furthermore, B chromosomes were detected in both mitosis and meiosis of hexaploid males and females, but not in sexual lineages. B chromosomes were consistently present and varied in number among individuals. B chromosomes varied in number and consistently formed univalents during meiosis, similar to other chromosomes. Significance statementMeiosis normally depends on chromosome pairing and recombination, yet asexual vertebrates can bypass these processes. We demonstrate that asexual hexaploid Carassius gibelio reproduces through achiasmatic meiosis, in which chromosomes fail to pair and recombine. While females successfully produce unreduced clonal eggs, males display reduced fertility, revealing striking sex-specific differences in the ability to overcome meiotic dysfunction. We further show that B chromosomes persist as meiotic univalents and are stably inherited.

genetics↗

bioRxiv2025

Insertion of an invading retrovirus regulates a novel color trait in swordtail fish

For over a century, evolutionary biologists have been motivated to understand the mechanisms through which organisms adapt to their environments. Coloration and pigmentation are remarkably variable within and between species and can serve as an important window into the mechanisms of adaptation. Here, we map the genetic basis of a newly described iridescence trait in swordtail fish to a single locus. Individuals with this trait appear to sparkle as they move through the water. We find that the trait is driven by the recent endogenization of a retrovirus that inserted near the gene alkal2a. This insertion is associated with changes in the chromatin landscape, upregulation of alkal2a, and accumulation of iridescent cells that adhere to the scales. Rather than causing diseases, our results demonstrate that invading endogenous retroviruses can also regulate novel trait variation in the host. Moreover, we find that this coloration trait may act as an important signal in interactions between fish and their predators in the natural environment.

evolutionary biology↗

bioRxiv2025

Hybridization Reveals Cell Type-Specific Regulatory Variation Driving Brain Transcriptomic Divergence

Gene expression is a molecular trait that can cumulatively contribute to more complex phenotypes. Interspecies hybrids have long been used to study the genetics basis of molecular, morphological and behavioral traits, to dissect interactions between cis- and trans-regulators with parental traits, and to uncover incompatible genetic interactions that drive extreme phenotypes in hybrid progeny. However, it remains unclear how organ functions at molecular level are affected by hybridization. We hypothesize that hybridization incited molecular level changes are cell type specific. To test this, we produced interspecies hybrid progeny from two distantly related fish species, Xiphophorus maculatus and couchianus. They are differing in mating, foraging behavior and likely neural circuits for cognition. We first performed allelic expression and bulk brain transcriptome profiling to identify expression quantitative trait loci (eQTLs) and quantitative transcript traits (QTTs) in order to quantify the scale and identify of loci contributing to gene expression variations in hybrids. It showed that QTT are predominantly influenced by additive eQTLs. Subsequently, we compared QTTs, which exemplify species-specific regulatory effects on gene expression, to cell type markers derived from single-nucleus RNA sequencing (snRNAseq). We identified 14 cell type-specific QTTs with known roles in brain functions. Overall, this study shows that transcriptomic phenotypes under species-specific regulators are associated to specific cell types in hybrids, and indicates the overall organ-level functional change could be driven by particular cell types.

genetics↗

bioRxiv2025

Comparison of Human Melanoma Single Cell Profiles to Evolutionary Medicine Model Xiphophorus Provides Insights In Disease Control

Melanoma remains one of the deadliest forms of cancer. Despite recent therapeutic advances including immune checkpoint inhibitors and small-molecule kinase inhibitors, patients frequently develop treatment resistance. Novel models are needed to devise strategies that overcome resistance and further reduce melanoma-related mortality. Interspecies hybrid fish from the Xiphophorus lineage develop mutant Epidermal Growth Factor Receptor (EGFR)-driven melanomas that display morphology, bulk gene expression, disease initiation and progression processes mimicking those of human melanomas. These similarities have enabled their comparative use in evaluating why human melanomas exhibit cancer cell plasticity, including dynamic transitions between proliferative and invasive states. However, it remains unclear whether Xiphophorus melanomas recapitulate some or all of these features. To address this, we performed single-nucleus RNA sequencing (snRNAseq) analysis of Xiphophorus melanomas. Multiple cancer cell types mirroring the human melanoma cell populations were identified, including proliferative cancer cells, dedifferentiated neural crest-like cells, mesenchymal-like cancer cells in addition to fibroblast, endothelial, and immune cells. Employing comparative analyses with results from human melanoma studies, it is demonstrated that Xiphophorus melanomas faithfully mimic the cellular heterogeneity observed in human melanoma.

genetics↗

bioRxiv2025

A Recessive oca2 Mutation Underlies Albinism in Xiphophorus fish

Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by impaired melanin production, leading to reduced pigmentation in the skin, hair, and eyes. Xiphophorus, a genus of small freshwater fish, has been a pivotal model organism in pigmentation disorder research, providing key findings in the genetic pathways governing physiological and pathological pigment cell biology. Leveraging the well-established research framework provided by Xiphophorus, we have identified a spontaneously occurring albinism phenotype in swordtail fish Xiphophorus hellerii. Genetic mapping of albino fish showed that albinism is associated with a recessive mutation in the oca2 gene. This discovery provides a novel opportunity to explore functions of oca2 gene in pigment cell differentiation, pigment synthesis, melanosome assembly and transportation function and amelanotic melanoma development.

genetics↗

bioRxiv2024

Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between diverged Xiphophorus species showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certain Xiphophorus species do not develop such tumors. Here we report the identification of a locus residing in the genome of one Xiphophorus species that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and molecular mechanism in hybrid incompatibility. SignificanceThe Dobzhansky-Muller model states epistatic interactions occurred between genes in diverged species underlies hybrid incompatibility. There are a few vertebrate interspecies hybrid cases that support the Dobzhansky-Muller model. This study reports a fish hybrid system where incompatible genetic interactions are involved in neuronal regulation of pigment cell biology, and also identified a novel point of regulation for pigment cells.

genetics↗

bioRxiv2024

Complex structural variation and behavioral interactions underpin a balanced sexual mimicry polymorphism

How phenotypic diversity originates and persists within populations are classic puzzles in evolutionary biology. While polymorphisms hypothesized to be under balancing selection segregate within many species, it remains rare for the genetic basis and the selective forces to both be known for the same trait, leading to an incomplete understanding of many classes of polymorphisms. Here, we uncover the genetic architecture of a balanced sexual mimicry polymorphism and identify behavioral mechanisms that may be involved in its maintenance in the swordtail fish Xiphophorus birchmanni. We find that [~]40% of X. birchmanni males develop a "false gravid spot", a melanic pigmentation pattern that mimics the "pregnancy spot" associated with sexual maturity in female live-bearing fish. Using genome-wide association mapping, we detect a single intergenic region associated with variation in the false gravid spot, which is upstream of kitlga, a gene involved in melanophore patterning. By performing long-read sequencing within and across populations, we identify complex structural rearrangements between alternate alleles at this locus. The false gravid spot haplotype drives increased allele-specific expression of kitlga, which provides a mechanistic explanation for the increased melanophore abundance that causes the spot. By studying social interactions in the laboratory and in nature, we find that males with the false gravid spot experience less aggression; however, they also receive increased attention from other males and are disdained by females. These behavioral interactions may play a role in maintaining this phenotypic polymorphism in natural populations. We speculate that structural variants affecting gene regulation may be an underappreciated driver of balanced polymorphisms across diverse species.

evolutionary biology↗

bioRxiv2024

Phylogenomics analyses of all species of Swordtails (Genus Xiphophorus) highlights hybridization precedes speciation

Hybridization has been recognized as an important driving force for evolution, however studies of the genetic consequence and its cause are still lagging behind in vertebrates due to the lack of appropriate experimental systems. Fish of the central American genus Xiphophorus were proposed to have evolved with multiple ancient and ongoing hybridization events, and served as a valuable research model in evolutionary biology and in biomedical research on human disease for more than a century. Here, we provide the complete genome resource and its annotation of all 26 Xiphophorus species. On this dataset we resolved the so far conflicting phylogeny. Through comparative genomic analyses we investigated the molecular evolution of genes related to melanoma, for a main sexually selected trait and for the genetic control of puberty timing, which are predicted to be involved in pre-and postzygotic isolation and thus to influence the probability of interspecific hybridization in Xiphophorus. We demonstrate dramatic size-variation of some gene families across species, despite the reticulate evolution and short divergence time. Finally, we clarify the hybridization history in the genus Xiphophorus genus, settle the long dispute on the hybridization origin of two Southern swordtails, highlight hybridizations precedes speciation, and reveal the distribution of hybridization ancestry remaining in the fused genome.

genomics↗

bioRxiv2023

Genome evolution is surprisingly predictable after initial hybridization

Over the past two decades, evolutionary biologists have come to appreciate that hybridization, or genetic exchange between distinct lineages, is remarkably common - not just in particular lineages but in taxonomic groups across the tree of life. As a result, the genomes of many modern species harbor regions inherited from related species. This observation has raised fundamental questions about the degree to which the genomic outcomes of hybridization are repeatable and the degree to which natural selection drives such repeatability. However, a lack of appropriate systems to answer these questions has limited empirical progress in this area. Here, we leverage independently formed hybrid populations between the swordtail fish Xiphophorus birchmanni and X. cortezi to address this fundamental question. We find that local ancestry in one hybrid population is remarkably predictive of local ancestry in another, demographically independent hybrid population. Applying newly developed methods, we can attribute much of this repeatability to strong selection in the earliest generations after initial hybridization. We complement these analyses with time-series data that demonstrates that ancestry at regions under selection has remained stable over the past [~]40 generations of evolution. Finally, we compare our results to the well-studied X. birchmannixX. malinche hybrid populations and conclude that deeper evolutionary divergence has resulted in stronger selection and higher repeatability in patterns of local ancestry in hybrids between X. birchmanni and X. cortezi.

evolutionary biology↗

bioRxiv2023

ADGRE5 ACTS AS A MELANOMA TUMOR SUPPRESSOR IN NATURALLY HYBRIDIZING XIPHOPHORUS.

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids. Melanoma development is due to hybrid inheritance of an oncogene, xmrk, and loss of a co-evolved tumor modifier. It was recently found that adgre5, a G protein-coupled receptor involved in cell adhesion, is a tumor regulator gene in naturally hybridizing Xiphophorus species X. birchmanni and X. malinche. We hypothesized that one of the two parental alleles of adgre5 is involved in regulation of cell proliferation, migration and melanomagenesis. Accordingly, we assessed the function of adgre5 alleles from each parental species of the melanoma-bearing hybrids using in vitro cell proliferation and migration assays. In addition, we expressed each adgre5 allele with the xmrk oncogene in transgenic medaka. We found that cells transfected with the X. birchmanni adgre5 exhibited decreased proliferation and migration compared to those with the X. malinche allele. Moreover, X. birchmanni allele of adgre5 completely inhibited melanoma development in xmrk transgenic medaka, while X. malinche adgre5 expression did not exhibit melanoma suppressive activity in medaka. These findings showed that adgre5 is a natural melanoma suppressor and provide new insight in melanoma etiology.

cancer biology↗

bioRxiv2023

A novel amphibian sex determination candidate gene, evolved by structural variation in the regulatory region between X and Y

Most vertebrates develop distinct females and males, where sex is determined by repeatedly-evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene is known in >8650 species, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW[female]/ZZ[male]). Combining chromosome-scale female and male genomes of a non- model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing revealed a candidate master locus, governing a male-heterogametic system (XX[female]/XY[male]). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5-regulatory region of the gene bod1l, where a Y-specific non-coding RNA, only expressed in males, suggests that this locus may initiate sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant, sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads with coinciding differential H3K4me- methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination.

genomics↗

bioRxiv2022

Transcriptional background effects on a tumor driver gene in a transgenic medaka melanoma model

The Xiphophorus melanoma receptor kinase gene, xmrk, is a bona fide oncogene driving melanocyte tumorigenesis of Xiphophorus fish. When ectopically expressed in medaka, it not only induces development of several pigment cell tumor types in different strains of medaka, but also induces different tumor types within the same animal, suggesting its oncogenic activity has a transcriptomic background effect. Although the central pathways that xmrk utilizes to lead to melanomagenesis are well documented, genes and genetic pathways that modulate the oncogenic effect, and alter the course of disease have not been studied so far. To understand how the genetic networks between different histocytes of xmrk-driven tumors are composed, we isolated two types of tumors, melanoma and xanthoerythrophoroma, from the same xmrk transgenic medaka individuals, established the transcriptional profiles of both xmrk-driven tumors, and compared (1) genes that are co-expressed with xmrk in both tumor types, and (2) differentially expressed genes and their associated molecular functions, between the two tumor types. Transcriptomic comparisons between the two tumor types show melanoma and xanthoerythrophoroma are characterized by transcriptional features representing varied functions, indicating distinct molecular interactions between the driving oncogene and the cell type-specific transcriptomes. Melanoma tumors exhibited gene signatures that are relevant to proliferation and invasion while xanthoerythrophoroma tumors are characterized by expression profiles related metabolism and DNA repair. We conclude the transcriptomic backgrounds, exemplified by cell-type specific genes that are downstream of xmrk effected signaling pathways, contribute the potential to change the course of tumor development and may affect overall tumor outcomes.

genetics↗

bioRxiv2021

A non-functional copy of the salmonid sex determining gene (sdY) is responsible for the "apparent" XY females in Chinook salmon, Oncorhynchus tshawytscha.

Many salmonids have a male heterogametic (XX/XY) sex determination system, and they are supposed to have a conserved master sex determining gene (sdY), that interacts at the protein level with Foxl2 leading to the blockage of the synergistic induction of Foxl2 and Nr5a1 of the cyp19a1a promoter. However, this hypothesis of a conserved master sex determining role of sdY in salmonids is still challenged by a few exceptions, one of them being the presence of some naturally occurring "apparent" XY Chinook salmon females. Here we show that XY Chinook salmon females have a sdY gene (sdY-N183), which has one missense mutation leading to a substitution of a conserved isoleucine to an asparagine (SdY I183N). In contrast, Chinook salmon males have both a non-mutated sdY-I183 gene and the missense mutation sdY-N183 gene. The 3D model of SdY-N183 predicts that the I183N hydrophobic to hydrophilic amino acid change leads to a local modification of the {beta}-sandwich structure of SdY. Using in vitro cell transfection assays we found that SdY-N183, like SdY-I183, is preferentially localized in the cytoplasm. However, compared to SdY-I183, SdY-N183 is more prone to degradation, its nuclear translocation by Foxl2 is reduced and SdY-N183 is unable to significantly repress the synergistic Foxl2/Nr5a1 induction of the cyp19a1a promoter. Altogether our results suggest that the sdY-N183 gene of XY Chinook females is a non-functional gene and that SdY-N183 is no longer able to promote testicular differentiation by impairing the synthesis of estrogens in the early differentiating gonads of wild Chinook salmon XY females.

genetics↗

bioRxiv2021

A Lethal Genetic Incompatibility between Naturally Hybridizing Species in Mitochondrial Complex I

The evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of "hybrid incompatibilities," where alleles derived from two different species no longer interact properly in hybrids. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes and that incompatibilities involving multiple genes should be common, but there has been sparse empirical data to evaluate these predictions. Here, we describe a mitonuclear incompatibility involving three genes in physical contact within respiratory Complex I in naturally hybridizing swordtail fish species. Individuals homozygous for specific mismatched protein combinations fail to complete embryonic development or die as juveniles, while those heterozygous for the incompatibility have reduced function of Complex I and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the impacts of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. We document the evolutionary history of the genes involved, showing for the first time that an incompatibility has been transferred between species via hybridization. This work thus provides the first glimpse into the genetic architecture, physiological impacts, and evolutionary origin of a complex incompatibility impacting naturally hybridizing species.

evolutionary biology↗

bioRxiv2020

A 180 My-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes

Several hypotheses explain the prevalence of undifferentiated sex chromosomes in poikilothermic vertebrates. Turnovers change the master sex determination gene, the sex chromosome or the sex determination system (e.g. XY to WZ). Jumping master genes stay main triggers but translocate to other chromosomes. Occasional recombination (e.g. in sex-reversed females) prevents sex chromosome degeneration. Recent research has uncovered conserved heteromorphic or even homomorphic sex chromosomes in several clades of non-avian and non-mammalian vertebrates. Sex determination in sturgeons (Acipenseridae) has been a long-standing basic biological question, linked to economical demands by the caviar-producing aquaculture. Here, we report the discovery of a sex-specific sequence from sterlet (Acipenser ruthenus). Using chromosome-scale assemblies and pool-sequencing, we first identified a ~16 kb female-specific region. We developed a PCR-genotyping test, yielding female-specific products in six species, spanning the entire phylogeny with the most divergent extant lineages (A. sturio, A. oxyrinchus vs. A. ruthenus, Huso huso), stemming from an ancient tetraploidization. Similar results were obtained in two octoploid species (A. gueldenstaedtii, A. baerii). Conservation of a female-specific sequence for a long period, representing 180 My of sturgeon evolution, and across at least one polyploidization event, raises many interesting biological questions. We discuss a conserved undifferentiated sex chromosome system with a ZZ/ZW-mode of sex determination and potential alternatives.

evolutionary biology↗

bioRxiv2020

Evolution of the canonical sex chromosomes of the guppy and its relatives

The sex chromosomes of the guppy, Poecilia reticulata, and its close relatives are of particular interest: they are much younger than the highly degenerate sex chromosomes of model systems such as mammals and Drosophila melanogaster, and they carry many of the genes responsible for the males dramatic coloration. Over the last decade, several studies have analyzed these sex chromosomes using a variety of approaches including sequencing genomes and transcriptomes, cytology, and linkage mapping. Conflicting conclusions have emerged, in particular concerning the history of the sex chromosomes and the evolution of suppressed recombination between the X and Y. Here we address these controversies by reviewing the evidence and reanalyzing data. We find no support for a nonrecombining sex determining region (SDR) or evolutionary strata in P. reticulata. Further, we find that the evidence most strongly support the hypothesis that the SDRs of P. picta and P. wingei evolved independently after those lineages diverged. We identify possible causes of conflicting results in previous studies and suggest best practices going forward.

genomics↗

bioRxiv2020

Decontextualized learning for interpretable hierarchical representations of visual patterns

SO_SCPLOWUMMARYC_SCPLOWApart from discriminative models for classification and object detection tasks, the application of deep convolutional neural networks to basic research utilizing natural imaging data has been somewhat limited; particularly in cases where a set of interpretable features for downstream analysis is needed, a key requirement for many scientific investigations. We present an algorithm and training paradigm designed specifically to address this: decontextualized hierarchical representation learning (DHRL). By combining a generative model chaining procedure with a ladder network architecture and latent space regularization for inference, DHRL address the limitations of small datasets and encourages a disentangled set of hierarchically organized features. In addition to providing a tractable path for analyzing complex hierarchal patterns using variation inference, this approach is generative and can be directly combined with empirical and theoretical approaches. To highlight the extensibility and usefulness of DHRL, we demonstrate this method in application to a question from evolutionary biology.

evolutionary biology↗