Biology subjects

Sommer, R. J.

Publications and source records attributed to Sommer, R. J..

At least 19 recordsLinked to original sources

bioRxiv2026

Terminal selector and subtype selector function across 200 million years of nematode evolution

The evolution of brains is subject to investigation in many different animal groups, each offering unique advantages to advance our understanding of the cellular, molecular and regulatory substrates of evolutionary change. Here, we use two nematode species, C. elegans and P. pacificus, separated by more than 200 million years of evolution to explore how neuronal cell types and the regulatory programs instructing the identity of these cell types have evolved over time. Using gene expression pattern analysis, we compare the differentiation programs of over half of all nematode neuron classes. To explore how the gene regulatory architecture of neuronal differentiation programs evolves, we apply our deep understanding of neuronal differentiation programs, controlled by terminal selectors and subtype selectors in C. elegans. Through mutant analysis of orthologous P. pacificus regulatory factors, we elucidate patterns of conservation and novelties over such substantial evolutionary distance. We discovered striking similarities in terminal selector expression and activities throughout the nervous system but also observed that terminal selectors can acquire novel sites of expression and distinct regulatory capabilities, manifested by changes in effector gene expression and, hence, neuronal phenotypes. Our mutant analysis argues for a buffering of terminal selector function and for an evolutionary lability of differences in closely related neuronal subtypes. Taken together, our analysis reveals molecular substrates of evolutionary change in nervous systems.

neuroscience↗

bioRxiv2026

A multifunctional polyketide synthase in nematodes produces divergent families of signaling molecules that control different developmental arrests

To improve their chances of reproductive success, nematodes not only must arrest their development in response to adverse growth conditions but also must quickly recover if conditions improve. A polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) hybrid assembly line that is expressed in the canal-associated neurons (CANs) of Caenorhabditis elegans promotes recovery from starvation-induced larval arrest. Here, we show that in the predatory nematode Pristionchus pacificus this assembly line produces a suite of secondary metabolites, including a family of hybrid polyketide-nonribosomal peptides known as the nemamides, the related nemaketides, and a family of ascarylose-modified polyketides named ascarenes. Depending on the starter unit that is loaded onto the PKS, the assembly line can produce dramatically different downstream products. Whereas the nemamides promote recovery from starvation-induced larval arrest, the ascarenes inhibit development of the dauer larval stage and promote recovery. This dichotomy suggests that the PKS-NRPS megasynthetase serves as a signaling hub in the CANs, controlling multiple developmental events. The PKS-NRPS assembly line is highly conserved across many nematode species, and identification of these chemical signals will help to elucidate the signaling pathways that control development in the worm and lead to novel anthelmintics.

biochemistry↗

bioRxiv2026

Evolutionary landscapes of zygotic genome activation across animals

During early animal embryogenesis, gene expression control shifts from maternally deposited products to newly transcribed RNA through zygotic genome activation (ZGA). Although essential and universal, ZGA remains poorly understood outside a few model species. Here, we generated a transcriptomic atlas of early embryogenesis across 61 animal species from 13 phyla and used a unified computational framework to infer ZGA timing systematically. We find extensive variation in ZGA onset across animals, but show that the ratio between genome size and egg cytoplasmic volume, a proxy for the nuclear-to-cytoplasmic ratio, robustly predicts when genome activation begins. We also reveal that zygotic genes also differ from maternal transcripts in genomic architecture, function and evolutionary conservation, suggesting that ZGA follows a conserved molecular logic despite flexible transcriptomic outputs.

evolutionary biology↗

bioRxiv2026

Evidence of a predator-prey co-evolutionary arms race within a nematode microhabitat

Predator-prey interactions are key drivers of behavioural and life-history evolution, yet their mechanisms remain difficult to study in natural contexts. The nematode Pristionchus pacificus is a model predator, but most studies exploring its behaviours use Caenorhabditis elegans as prey, a species that it likely only rarely encountered in nature. Here, we examine predation within nematode communities associated with beetle carcasses, the native necromenic habitat of P. pacificus. We identify Oscheius myriophilus as a cohabiting species, likely representing natural prey. Using predatory assays, automated tracking, and machine-learning-based behavioural analysis, we show that P. pacificus actively kills and consumes O. myriophilus. Strikingly, predation rates are lower than those observed for C. elegans, suggesting partial resistance or reciprocal adaptation in O. myriophilus. Consistent with this, O. myriophilus exhibits a mixed reproductive strategy, with early oviposition followed by ovoviviparity and matricide. As later developmental stages are more resistant to predation, internal hatching may protect offspring while providing maternal resources for development. These findings establish these nematodes as a tractable model for investigating predator-prey interactions and their evolutionary consequences, highlighting how behavioural strategies and life-history traits can co-evolve in natural communities.

evolutionary biology↗

bioRxiv2026

Plasticity in nonsense-mediated decay and translation initiation regulate polyphenism

Developmental plasticity is increasingly recognised as facilitator of evolutionary novelty. However, how plasticity itself evolves and how variation in plastic trait expression is structured in populations remain unknown1,2. The predatory nematode Pristionchus pacificus exhibits mouth-form plasticity with underlying molecular mechanisms being increasingly identified3. We investigate the temporal scale of natural variation of mouth-form plasticity. An 11-year survey characterised Adoretus beetle-derived isolates from Colorado, La Reunion Island and revealed a gradual shift in mouth-form preference. Quantitative trait locus mapping of mouth-form preferences identified a single peak harbouring the developmental switch gene eud-1. Through CRISPR-engineering and biochemical assays, we show that plasticity in nonsense-mediated decay coupled with alternative start codon selection resulting in different N-terminal proteoforms of EUD-1 are associated with natural variation of mouth-form preference. This work provides molecular explanations for variation in plastic trait expression and links nonsense variants in the major developmental switch locus to ecological and evolutionary processes.

evolutionary biology↗

bioRxiv2026

A unique Cysteine-type protein domain regulates cuticular extracellular matrix assembly in nematodes

Apical extracellular matrices (aECMs) act as barriers against pathogens and shape tissue organization throughout animals. In nematodes, the cuticle is the aECM performing this function, representing a defining feature of this largest animal phylum. Morphological and molecular evidence supports that worm cuticles extend from the head into the mouth, the latter contributing to the large diversity of nematode feeding structures. However, the biochemical understanding of the compositions of nematode cuticles and head structures is largely limited to collagens. Here, we characterized a recently identified mucin-type protein DPY-6 as a constituent of the cuticle and mouth in the model organisms Pristionchus pacificus and Caenorhabditis elegans. Utilizing bioinformatic tools, we discover a unique cysteine-consisting motif at the N-terminus of DPY-6 with the amino acid sequence CxCxCxC. We demonstrate through in vitro biophysical experiments that this cysteine motif facilitates the intermolecular dimerization of DPY-6 proteins. In vivo studies in both species reveal that this motif is involved in the proper localization of the protein in the cuticle, but functions synergistically with other protein domains in a species-specific manner. Given that dpy-6 transcriptomic expression precedes other cuticle components, we speculate that DPY-6 acts as scaffold molecule for nematode cuticular aECM formation.

biochemistry↗

bioRxiv2026

Lessons learned from manual curation of thousands of gene models in the nematode Pristionchus pacificus

Continuous developments in sequencing technologies have led to the generation of chromosome-scale genome assemblies across the whole tree of life, but our ability to annotate genomes has lacked behind. One major problem consists in the fact that typically not all genes are expressed at detectable levels at any given life stage or environment. Therefore, available transcriptome data needs to be complemented by gene prediction programs and protein homology evidence. However, how to optimally combine these different data types is not well understood. Here, we present a case study, where we community curated gene annotations of the Pristionchus pacificus strain RSC011. By incorporation of new Iso-seq and RNA-seq data and genome-wide screening, we identified and corrected more than 7,500 ([~]24%) gene models. While the improved gene annotation for the RSC011 strain will be useful for the P. pacificus community, our study reveals several gene annotation problems that may affect data from other species. Among these, we identified assembly errors, artificial transcript fusions resulting from overlapping genes and polycistronic RNAs, falsely called open reading frames, and error propagation based on homology data as frequent sources of gene annotation errors. Thus, our findings may be helpful in guiding future efforts to annotate genomes across different taxonomic groups.

genomics↗

bioRxiv2026

The topology of ecological drift

Ecological drift, the random fluctuation of abundance in communities, can drastically affect the possibility of coexistence. However, ecological drift has mostly been considered at the macro-ecological scale, whereas its potential contribution to short-term ecological dynamics remains underexplored. Here, we propose a stage-structured ecological graph theory (ssEcoGT) to include complex life cycles and multiple ecological interactions to study the topology of ecological drift. ssEcoGT enables rigorous exploration of how topology of a community can affect the possibility of coexistence between two species. Using ssEcoGT, it is possible to compare the behavior of a range of models - e.g., random graphs, random graphs with intraguild predation, and random graphs with rewiring - against a complete graph of the same size. Thus, ssEcoGT provides a new tool to explore the interplay between ecological drift, competition, and stage-specific interactions.

ecology↗

bioRxiv2025

Adaptive consequences of transgenerational inheritance of a predatory mouth-form trait in nematodes

A growing body of evidence suggests that environmentally-induced changes in phenotypes can cross the generation barrier and associated molecular mechanisms are being increasingly identified. Such transgenerational epigenetic inheritance (TEI) is repeatedly considered to be adaptive although experimental support for this claim is often missing. We study the adaptive consequences of TEI in the facultative predatory nematode Pristionchus pacificus, which can form two alternative mouth forms dependent on environmental conditions. The choice of feeding structure in P. pacificus can be manipulated through dietary switching and food reversal. Recent studies showed that certain diets cause the induction of the predatory mouth form, which can result in TEI after food reversal. This memory requires the ubiquitin ligase EBAX-1/ZSWIM8 and the destabilization of clustered microRNAs. To study the adaptive potential of transgenerational memory of the predatory morph, we measured brood size as proxy for fitness. We compared naive worms, with those under dietary induction and food reversal, and found a fitness advantage for animals exhibiting TEI of the predatory morph. Specifically, after food reversal worms had higher lifetime reproductive success for up to three generations when compared to diet-induced or naive worms. These results support the adaptive significance of non-genetic inheritance of the predatory trait.

evolutionary biology↗

bioRxiv2025

Diet-derived vitamin B12 induces transgenerational inheritance of nematode predation through elevated vitellogenin provisioning

Dietary and nutritional effects can alter organismal phenotypes and influence trait inheritance over generations, so-called transgenerational epigenetic inheritance. However, the chemical nature of the stimuli and the downstream events inducing such memory remain largely elusive. The nematode Pristionchus pacificus exhibits mouth-form plasticity including predation and was recently shown to respond to a multigenerational Novosphingobium diet with the induction and subsequent transgenerational inheritance of the predatory morph. Here, we show that bacteria-derived vitamin B12 is both necessary and sufficient for transgenerational memory. Different vitamin B12 concentrations are required for the original induction and the subsequent transgenerational inheritance of the predatory morph. Mutant analysis revealed that vitamin B12 functions through methionine-synthase and involves methionine but not vitamin B9. The inherited effect acts through increased multigenerational vitellogenin transcription indicating elevated nutrient provisioning. Consistently, mutants in the vitellogenin receptor Ppa-rme-2 are memory-defective. Thus, vitamin B12 induces vitellogenin provisioning to control organismal physiology and behavior.

genetics↗

bioRxiv2025

The dynamics of coexistence and succession in a decaying ecosystem

Elucidating the rules that govern community assembly and enable the coexistence of species is central to ecology. Much of the current understanding revolves around the composition of communities at equilibrium. In contrast, transient ecological dynamics, in particular the succession of species following an environmental disturbance, remain largely unexplored. We present Gymnogaster buphthalma beetle carcasses as a model to study species coexistence in disequilibrium. In this community, nematodes appear in succession - with multiple feeding and reproductive strategies, transience, and associated dispersal - creating a perfect model for metacommunity ecology. We computationally reconstructed decaying G. buphthalma beetles sampled from the wild using experimentally-derived life history data, i.e. emergence times, sex ratios, and fecundity measurements. Through agent-based modeling, we show that nematode coexistence is possible over a wide range of scenarios. This work provides a unique experimental and computational framework to synthesize various approaches to metacommunity and species succession theories.

ecology↗

bioRxiv2025

Biosynthesis of modular signaling molecules requires functional diversification of carboxylesterases in Pristionchus pacificus

The model nematode Pristionchus pacificus produces four types of complex ascaroside pheromones named UBAS, DASC, NPAR, and PASC. However, the exact biosynthetic pathways of these modular signaling molecules remain enigmatic. We have previously identified a carboxylesterase Ppa-UAR-1 for the biosynthesis of UBAS, enabling the attachment of ureidoisobutyric acid at the 4-position of simple ascarosides. Here, we report three new carboxylesterases Ppa-UAR-5, Ppa-UAR-6 and Ppa-UAR-12 from P. pacificus. Ppa-UAR-5 functions downstream of Ppa-UAR-1 to furnish the biosynthesis of ubas#1 and ubas#2, whereas Ppa-UAR-12 specifically links two ascr#1 at the 4-position to synthesize dasc#1. Finally, Ppa-UAR-6 is essential for the biosynthesis of npar#1-3 and part#9. The expression patterns of Ppa-uar-6 and Ppa-uar-12 in the intestinal and epidermal cells suggest pheromone biosynthesis to be restricted to specific tissues. These findings indicate that the expansion and functional diversification of carboxylesterases plays a crucial role in the evolution of complex pheromones in nematodes. SIGNIFICANCEOur study identified three new carboxylesterase genes (Ppa-uar-5, Ppa-uar-12 and Ppa-uar-6) from P. pacificus. The encoded enzymes separately regulated the biosynthesis of three types of modular pheromones (UBAS, DASC, and NPAR-types) in worms intestinal cells and exhibited extremely high substrate-specificity. For example, we verified that Ppa-UAR-12 specifically linked one ascr#1 to the 4-position of another ascr#1 to finally furnish the biosynthesis of ascaroside dimer dasc#1. These new discoveries largely clarify the delicate biosynthetic mechanisms of how diversification of carboxylesterases functions in P. pacificus to build up enormous complexity of modular signaling molecules. Such a biosynthetic mechanism of nematode pheromones might be widely conserved in the phylum Nematoda.

biochemistry↗

bioRxiv2024

Developmental transcriptomics in Pristionchus reveals the logic of a plasticity gene regulatory network

Developmental plasticity enables the production of alternative phenotypes in response to different environmental conditions. While significant advances in understanding the ecological and evolutionary implications of plasticity have been made, understanding its genetic basis has lagged. However, a decade of genetic screens in the model nematode Pristionchus pacificus has culminated in 30 genes which affect mouth-form plasticity. We also recently reported the critical window of environmental sensitivity, and therefore have clear expectations for when differential gene expression should matter. Here, we collated previous data into a gene-regulatory network (GRN), and performed developmental transcriptomics across different environmental conditions, genetic backgrounds, and mouth-form mutants to assess the regulatory logic of plasticity. We found that only two genes in the GRN (eud-1 and seud-1/sult-1) are sensitive to the environment during the critical window. Interestingly, the time points of their sensitivity differ, suggesting that they act as sequential checkpoints. We also observed temporal constraint upon the transcriptional effects of mutating the GRN and revealed unexpected feedback between mouth-form genes. Surprisingly, expression of seud-1/sult-1, but not eud-1, correlated with mouth form biases across different strains and species. Finally, a comprehensive analysis of all samples identified metabolism as a shared pathway for regulating mouth-form plasticity. These data are presented in a Shiny app to facilitate gene-expression comparisons across development in up to 14 different conditions. Collectively, our results suggest that mouth-form plasticity evolved a constrained, two-tiered logic to integrate environmental information leading up to the final developmental decision.

genetics↗

bioRxiv2024

EBAX-1/ZSWIM8 destabilizes miRNAs resulting in transgenerational memory of a predatory trait

Environmental influences on traits and associated transgenerational epigenetic inheritance have widespread implications, but remain controversial and underlying mechanisms poorly understood. We introduce long-term environmental induction experiments on alternative diets in Pristionchus pacificus, a nematode exhibiting mouth-form plasticity including predation, by propagating 110 isogenic lines for 101 generations with associated food-reversal experiments. We found dietary induction and subsequent transgenerational memory of the predatory morph and identified a role of ubiquitin ligase EBAX-1/ZSWIM8 in this process. Ppa-ebax-1 mutants have no memory and Ppa-EBAX-1 destabilizes the clustered microRNA family miR-2235a/miR-35. Deletions of a cluster of 44 identical miR-2235a copies resulted in precocious and extended transgenerational inheritance of the predatory morph. These findings indicate that EBAX-1/ZSWIM8 destabilizes miRNAs resulting in transgenerational memory, suggesting a role for target-directed miRNA degradation.

genetics↗

bioRxiv2024

Functional divergence of conserved developmental plasticity genes between two distantly related nematodes

Genes diverge in form and function in multiple ways over time; they can be conserved, acquire new roles, or eventually be lost. However, the way genes diverge at the functional level is little understood, particularly in plastic systems. We investigated this process using two distantly related nematode species, Allodiplogaster sudhausi and Pristionchus pacificus. Both these nematodes display environmentally-influenced developmental plasticity of mouth-form feeding structures. This phenotype can be manipulated by growth on particular diets, making them ideal traits to investigate functional divergence of developmental plasticity genes between organisms. Using CRISPR-engineered mutations in A. sudhausi mouth-form genes, we demonstrate examples of the various ways ancestral genes regulate developmental plasticity and how these roles can progressively diverge. We examined four ancestral genes, revealing distinct differences in their conservation and functional divergence in regulating the mouth phenotype in both species. Specifically, certain genes retain the same characteristics, while others have acquired a new function. Additionally, two ancestral genes retain their functions as switch genes, which completely prevent a phenotype, and the other two display quantitative effects, with knockouts in these genes displaying intermediate phenotypes. Remarkably, despite the evolutionary distance, all genes examined were involved in mouth-form regulation. Finally, multiple gene knock-out mutants were engineered, with key sulfatase-encoding genes acting downstream of all others, suggesting they play a major role in mouth-form plasticity. Together, this study represents the first mutant-based functional analysis of the evolution of developmental plasticity between two highly diverged species, offering new insights into the genetic mechanisms underlying phenotypic evolution. Article SummaryWhile evolutionary divergence of genes is well-studied at the sequence level, the resulting functional and phenotypic consequences are less known, particularly in plastic systems. Here, we examined functional divergence of a set of genes involved in developmental plasticity of mouth-form between two highly diverged nematode species. We found that all studied genes control mouth-form plasticity in both species; however, with strong functional divergence and gene-specific quantitative effects or even novel functions. Thus, there is a spectrum from full conservation, partial conservation to the gain of a new function; with genes involved in sulfation showing the strongest conservation during evolution.

evolutionary biology↗

bioRxiv2024

High nutritional conditions influence feeding plasticity in Pristionchus pacificus and render worms non-predatory

Developmental plasticity, the ability of a genotype to produce different phenotypes in response to environmental conditions, has been subject to intense studies in the last four decades. The self-fertilizing nematode Pristionchus pacificus has been developed as a genetic model system for studying developmental plasticity due to its mouth-form polyphenism that results in alternative feeding strategies with a facultative predatory and a non-predatory mouth form. Many studies linked molecular aspects of the regulation of mouth-form polyphenism with investigations of its evolutionary and ecological significance. Also, several environmental factors influencing P. pacificus feeding structure expression were identified including temperature, culture condition and population density. However, the nutritional plasticity of the mouth form has never been properly investigated although polyphenisms are known to be influenced by changes in nutritional conditions. For instance, studies in eusocial insects and scarab beetles have provided significant mechanistic insights into the nutritional regulation of polyphenisms but also other forms of plasticity. Here, we study the influence of nutrition on mouth-form polyphenism in P. pacificus through experiments with monosaccharide and fatty acid supplementation. We show that in particular glucose supplementation renders worms non-predatory. Subsequent transcriptomic and mutant analyses indicate that de novo fatty acid synthesis and peroxisomal beta-oxidation pathways play an important role in the mediation of this plastic response. Finally, the analysis of fitness consequences through fecundity counts suggests that non-predatory animals have an advantage over predatory animals grown in the glucose-supplemented condition. Research highlightsThis study represents the first systematic attempt to investigate the influence of nutrition on mouth-form polyphenism in the genetic model organism Pristionchus pacificus. Through glucose and oleic acid supplementation we show that high nutritional conditions influence feeding plasticity and render worms non-predatory. Mutant analysis indicates a role of de novo fatty acid synthesis and peroxisomal beta-oxidation pathways for these responses.

evolutionary biology↗

bioRxiv2024

The genome assembly of Rhabditoides inermis from a complex microbial community reveals further evidence for parallel gene family expansions across multiple nematodes

BackgroundFree-living nematodes such as Caenorhabditis elegans and Pristionchus pacificus are powerful model systems for linking specific traits to their underlying genetic basis. To trace the evolutionary history of a candidate gene, a robust phylogenomic framework is indispensable. ResultsIn this work, we generated a near chromosome-scale genome assembly of the nematode Rhabditoides inermis which had previously been proposed as the sister group of the family Diplogastridae to which P. pacificus belongs. The genome was assembled from a complex microbial community that consists of multiple bacteria and a fungus of the genus Vanrija. The R. inermis genome has five chromosomes that likely arose from recent fusions of different Nigon elements. Phylogenomic analysis grouped R. inermis within a clade including C. elegans, Mesorhabditis belari and other rhabditids and thus, did not support a sister group relationship between R. inermis and the family Diplogastridae. Comparative genomic analyses identified abundant lineage-specific orthogroups which reveal evidence for parallel expansions of environmentally responsive gene families. ConclusionsOur work demonstrates the value of the R. inermis genome as a resource for future phylogenomic analysis and for studying gene family evolution.

genomics↗

bioRxiv2024

Developmental small RNA transcriptomics reveals divergent evolution of the conserved microRNA miR-100 and the let-7-complex in nematodes

BackgroundOver the last three decades, small RNAs have emerged as one of the key post-transcriptional regulators, and are categorised into microRNAs (miRNAs), small interfering RNAs (siRNAs), and PIWI-interacting RNAs (piRNAs). Since their discovery as regulators of developmental timing in the nematode Caenorhabditis elegans, some miRNAs have been found to be highly conserved throughout animal evolution. miR-100 is one such highly conserved miRNA, possibly predating the origin of bilaterians. Furthermore, mir-100 is a member of the conserved let-7-complex, a locus containing three conserved miRNA-coding genes (mir-100, let-7, and mir-125/lin-4) that does not exist in the same arrangement in C. elegans. ResultsWe performed small RNA sequencing across four developmental time-points in the satellite nematode Pristionchus pacificus, identifying 64 novel and ontogenically specifically expressed miRNAs. We also identified miR-100 as the most abundant miRNA in post-embryonic juvenile stages. Additionally, P. pacificus exhibited a novel constellation of the let-7-complex, wherein mir-100 is closely linked to let-7, but without mir-125/lin-4 in the same locus. Mutants of mir-100 and let-7, individually as well as simultaneously, resulted in viable but developmentally defective worms, showing misregulation in collagen and astacin gene families. Interestingly, lin-4 mutants showed a delayed but otherwise normal development. ConclusionThis study provides the first developmental small RNA transcriptome of P. pacificus, providing a community resource for future evo-devo studies. Furthermore, we identify miR-100 as the most abundant ontogenically-specific miRNA, which, along with let-7, regulates normal development in P. pacificus. Lastly, we observe two alternative arrangements of the highly conserved miRNA locus let-7-complex.

evolutionary biology↗