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Stevens, L.

Publications and source records attributed to Stevens, L..

At least 19 recordsLinked to original sources

Evolutionary adaptation of helminth immunomodulators to their hosts

Background: Parasitic nematodes have evolved secreted effector proteins which interact with host molecules to modulate the host immune response. These interactions can be highly specific and are under strong selective pressure. Here, we investigate the host-pathogen interaction between Heligmosomoides bakeri and its natural host Mus musculus, and between H. polygyrus and its natural host Apodemus sylvaticus. We focus on the Alarmin Release Inhibitor family (previously called HpARI) produced by heligmosomid parasites, which interact with IL-33 and heparan sulphate. Results: Using comparative genomics, we identified duplications and diversifications of the ARI family including multiple copies of ARI1 and conserved ARI3 homologues in both H. bakeri and H. polygyrus. We identify a new family member, HpolARI4, encoded by H. polygyrus, as well as a more distant homologue, HmixARI, encoded by Heligmosomum mixtum, a parasite of the bank vole (Myodes glareolus). Our functional assays identify that HpolARI4 preferentially blocks A. sylvaticus IL-33 but has little activity against M. musculus IL-33, whereas HbakARI2 is highly specific for M. musculus IL-33. We furthermore show differential interaction with host heparan sulphate, with HbakARI2 and HpolARI4 showing high affinity binding, whereas HbakARI3 shows no binding. We further test this family against non-host human IL-33 and show that functional suppression can be achieved by HbakARI3 in vitro and in vivo. Conclusion: By integrating genomic data, structural insights, and functional assays, we reveal how the expansion and diversification of the ARI family drive host-specific IL-33 modulation, providing a molecular model for nematode-host co-evolution.

immunology↗

Massive programmed DNA elimination during embryogenesis in the trioecious nematode Auanema rhodense

In animals, the germline is usually set aside early in development and its genome is protected to ensure faithful transmission of genetic information to future generations. Genetic alterations in somatic cells are not inherited by progeny, and the somatic genome does not have to be protected from change in the same way. In some species, programmed DNA elimination (PDE) results in the directed loss of genetic material from somatic cells. Here, we report extreme PDE in Auanema rhodense, a free-living nematode with a remarkable, trioecious life history and unusual patterns of sex chromosome inheritance. We find that nearly two thirds of the A. rhodense germline genome is eliminated from somatic cells, with DNA lost from chromosome ends as well as within chromosomes, resulting in fragmentation of the seven germline chromosomes into fourteen somatic chromosomes. Most eliminated DNA comprises multi-megabase tandem repeat blocks. Eliminated DNA on the X chromosome harbours germline-restricted repeats that are distinct from those on the autosomes. The eliminated DNA includes many highly-repeated non-coding RNA loci but few protein-coding genes. Elimination sites are strongly associated with a palindromic sequence motif that likely directs DNA breakage and new telomere repeat array addition. Cytologically, PDE begins at the 12-cell stage of embryogenesis, is synchronous across all chromosomes, and is characterised by the formation of transient micronucleus-like bodies. Together, these findings reveal unusually extensive PDE in a free-living nematode and raise the possibility that germline-restricted repeat architecture may contribute to the atypical sex chromosome inheritance observed in Auanema.

genomics↗

Hidden in the genomic bycatch: insights into genome reorganization and population structure of the parasitic nematode Contortylenchus reversus

Insect-parasitic nematodes are widespread and often significantly reduce host fitness, yet we know surprisingly little about most species. Contortylenchus reversus is a hemocoel-inhabiting parasitic nematode that infects Dendroctonus bark beetles, notably impacting host mobility and fecundity. We first detail a chromosome-scale genome assembly of C. reversus, recovered serendipitously from a sequencing project targeting a host (Dendroctonus ponderosae). We assembled the 79.4 Mb genome into nine linkage groups and, through transcriptome-aided annotation, identified 11,244 protein-coding genes. Synteny comparisons with the only relatives for which there are complete assemblies reveal extensive chromosomal rearrangements and extreme loss of gene collinearity suggesting these insect-parasitic nematodes may have exceptionally malleable genomes. Using this genome assembly and repurposed reduced-representation genomic data from 707 D. ponderosae individuals, we investigated infection frequencies and population structure, identifying infection rates ranging from 0% to 50% across 18 geographically widespread collection sites. Population structure of C. reversus appears broadly concordant with the structure of the host beetle, suggesting a shared evolutionary history, while genetic variation (nucleotide diversity) in the parasitic nematode is highly reduced in comparison to its host. These results offer insights into its population genetics, host associations, and the evolutionary dynamics of a nematode-beetle interaction and highlight how genomic bycatch can reveal previously hidden details about an important species in a complex community.

genomics↗

Global genomic diversity of the selfing nematode Caenorhabditis tropicalis correlates with geography

Self-fertilization reduces genetic diversity compared to outcrossing and hypothetically decreases the ability to adapt to diverse environments. Among Caenorhabditis nematodes, self-fertilization evolved three times independently in Caenorhabditis elegans, Caenorhabditis briggsae, and the more recently discovered Caenorhabditis tropicalis. To survey C. tropicalis genetic relatedness, the influence of geography and niche on species-wide variation, and the signatures of selection, we collected 785 wild strains, sequenced their genomes, and identified 622 distinct genotypes (isotypes). In contrast to C. elegans and C. briggsae, C. tropicalis relatedness shows substantial association with geography and no transcontinental selective sweeps or broadly sampled isotypes. Populations from the Hawaiian Islands or Taiwan harbor more genetic variation than populations from the Caribbean or Americas, suggesting a Pacific species origin similar to other members of the Elegans subclade. Punctuated genomic regions of extreme genetic variation pervade the genome. These hyper-divergent regions (HDRs) comprise less than 6% of the reference genome in any given strain despite harboring 73% of all variant sites and are enriched for genes likely involved in environmental adaptation. HDRs represent a shared genomic feature of self-fertilizing Caenorhabditis nematodes despite their independent evolutionary origins and suggest a mechanism to explain worldwide distributions despite low species-wide levels of genetic variation.

genomics↗

Chromosome-level genome assembly and annotation of the parthenogenetic nematode Acrobeloides nanus

Acrobeloides nanus is a species of widely distributed bacteria-feeding nematodes belonging to the family Cephalobidae. It reproduces parthenogenetically, making it a valuable system for studying the consequences of obligate asexuality, and exhibits early developmental processes that differ significantly from the model organism Caenorhabditis elegans. Additionally, the species has demonstrated remarkable resistance in extreme conditions, surviving near-complete desiccation through anhydrobiosis. This new chromosome-level genome assembly provides a high-quality reference to study these traits. Combining Nanopore, amplified PacBio HiFi, and Hi-C sequencing, we generated a chromosome-level assembly spanning 188.9 Mb over six chromosomes. The genome features a 48.1% repeat content, dominated by Mutator-like elements, and contains 24,912 predicted genes. Structural analysis reveals the conservation of ancestral nematode linkage groups. This resource significantly improves upon previous fragmented assemblies, offering a new framework for identifying genomic adaptations in the family Cephalobidae.

genomics↗

Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication

Mental illnesses associated with high-risk copy number variations (CNVs) are characterized by incomplete penetrance and variable severity, with their underlying mechanisms remaining inadequately understood. We hypothesized that such phenotypic variability is evident from the neonatal stage and is, at least in part, attributable to individual differences in the expression levels of CNV-encoded genes in the brain. We conducted an analysis of the quantitative and functional structure of neonatal social communication, assessed post-pubertal social interaction, and evaluated the brain expression levels of genes within the same cohort of a mouse model of paternal human 15q11-13 duplication, a high-risk factor variably associated with neurodevelopmental disorders. Subsequently, computational methods were utilized to identify predictive variables for the variability of post-pubertal social interaction. Mice harboring the 15q11-13 duplication exhibited distinctive call sequences characterized by diverse connections, which lacked the incentive value necessary for effective social communication with mother mice. The neonatal call sequences and the expression levels of Magel2, along with, to a lesser extent, Herc2 and Ndn, in the prefrontal cortex of the 15q11-13 duplication model were predictive of post-pubertal social interaction. Our findings demonstrate that variability in post-pubertal social interaction--a dimensional characteristic of neurodevelopmental disorders--can be predicted by the variability of neonatal social communication and is influenced by the expression levels of specific CNV-encoded genes in the prefrontal cortex. This computational approach has the potential to predict the developmental trajectories of various dimensions of mental illness among CNV carriers in humans and to identify CNV-encoded driver genes in preclinical models, thereby providing potential mechanistic bases for the development of gene-based therapeutic strategies.

neuroscience↗

Panagrolaimus einhardi sp. nov. and two sisters of fortune

Identifying nematodes to the species level is known to be complicated due to their morphological plasticity and limited number of taxonomically important characters. This is especially apparent in the genus Panagrolaimus, which comprises many cryptic species that are morphologically difficult to distinguish but differ genetically. These roundworms are particularly notable for their adaptation to extreme environments that are inhospitable to many other forms of life. Traditional morphological identification methods often fail at distinguishing genetically divergent populations due to high morphological plasticity in Panagrolaimus, limiting the efficacy of species discovery. High-quality genome assemblies overcome these challenges, offering a comprehensive blueprint of an organisms genetic structure that can be used for species identification. The analysis of ultra-conserved elements across multiple loci harvested from genome assemblies provides robust phylogenetic resolution. In this study, we integrate genome sequencing, ultra-conserved element analysis, and morphological assessment to identify and describe three novel species: Panagrolaimus einhardi sp. nov., formerly Panagrolaimus sp. ES5 from Germany; Panagrolaimus shuimeiren sp. nov. from the Namib Desert; and Panagrolaimus nebliphilus sp. nov. from the Atacama Desert. P. einhardi sp. nov. is named after Prof. Einhard Schierenberg, a renowned expert in roundworm development and cherished member of the nematode community, who isolated this species himself. All three species originate from different geographical locations, and their respective identification are supported by high-quality genome assemblies from either PacBio HiFi or Oxford Nanopore long-read data. The P. einhardi sp. nov. genome was scaffolded using Hi-C technology, which resulted in a 116 Mb collapsed assembly composed of 44 scaffolds (N50: 28 Mb). P. shuimeiren sp. nov. has an assembly size of 69 Mb with 49 scaffolds and a N50 of 13 Mb. P. nebliphilus sp. nov. assembly is 70 Mb with 24 scaffolds (N50: 13 Mb). The capacity of Panagrolaimus to adapt to extreme environments is driving research into their survival mechanisms, requiring comprehensive genomic resources. By combining morphology and genomics, we can gain a more comprehensive understanding of the rich biological diversity in lineages with numerous cryptic species, such as the Panagrolaimidae, thereby clarifying relationships where morphological data alone are ambiguous or confounded.

zoology↗

Natural variation suggests candidate genes underlying Caenorhabditis elegans susceptibility to diverse toxicants

Genetic differences among individuals shape how they respond to environmental toxicants, but the identification and validation of the genes responsible for this variation is difficult, particularly in humans. Consequently, our limited knowledge of the genes that influence susceptibility constrains our ability to accurately predict the risks posed by environmental toxicants. To identify genes underlying natural differences in toxicant susceptibilities, we measured the effects of 23 environmental toxicants on larval development across 195 genetically diverse Caenorhabditis elegans strains using a high-throughput imaging platform. We then combined these response data with whole-genome sequences to perform genome-wide association mappings, identifying 40 genomic regions where genetic variants are correlated with susceptibility differences. Many of these regions are enriched for genes involved in biological processes previously linked with toxicant responses, supporting the potential contributions of these genes to natural variation in susceptibility. Using a set of heuristics, we identified 94 candidate susceptibility genes, offering targets for experimental validation that could ultimately inform toxicant risk prediction and regulatory assessment by linking genetic variation to differences in susceptibility. Impact StatementAnalysis of natural genetic variation among 195 wild C. elegans strains identified 94 candidate genes putatively linked to differences in susceptibility to 23 environmental toxicants. These findings can inform the discovery of conserved susceptibility genes and the development of biomarkers that improve chemical risk assessment by accounting for genetic differences among humans.

pharmacology and toxicology↗

ADAR RNA editing for cardiovascular disease: Targeting B4GALT1 to modulate lipid metabolism through reduced galactosyltransferase activity

Cardiovascular disease remains a leading cause of mortality despite current therapies targeting low-density lipoprotein cholesterol (LDL-C). Beta-1,4-galactosyltransferase 1 (B4GALT1), a central glycosyltransferase enzyme that regulates lipoprotein metabolism and hemostasis, is a promising therapeutic target. To evaluate its therapeutic potential as a protective variant, B4galt1 p.Asn352Ser was introduced into the ribonucleic acid (RNA) of healthy wild-type and APOE*3-Leiden.CETP transgenic mice, a well-established model for hyperlipidemia with a humanized lipoprotein metabolism, using editing oligonucleotides and the endogenous adenosine deaminases acting on RNA enzymes. The impact on hepatic glycosylation and systemic lipid homeostasis was investigated using multi-omics profiling. Editing of B4galt1 messenger RNA ([~]9-18%) resulted in substantial reductions in total cholesterol (-61%), apolipoprotein B (-72%), LDL-C (-30%), fibrinogen (-55%) (all p < 0.05), and triglycerides (-28%; p > 0.05), without altering B4galt1 expression. Proteomics of plasma and liver identified early suppression of lipogenesis and lipoprotein assembly, followed by sustained suppression of cholesterol biosynthesis and coagulation pathways. Glycomic analysis revealed remodeling of circulating glycoprotein architecture, consistent with altered B4GALT1 activity. Transcript-protein concordance was strongest in lipid pathways, while glycosylation and coagulation showed domain-specific regulatory patterns. These findings support targeting B4GALT1 using RNA editing to reduce cardiometabolic risk.

genetics↗

Programmed DNA elimination was present in the last common ancestor of Caenorhabditis nematodes

In most organisms, all cells inherit the same genome, and many mechanisms exist to preserve its integrity across cell divisions. Programmed DNA elimination (PDE), the targeted removal of specific genomic regions from somatic cell lineages during early embryogenesis, is a striking exception. Since its discovery in parasitic nematodes over a century ago, PDE has been observed in diverse eukaryotes, including ciliates, arthropods, and vertebrates. However, the mechanisms, functions, and evolutionary origins of PDE remain poorly understood. Here, we describe the discovery of PDE in three species of the free-living nematode genus Caenorhabditis. Multiple genomic regions are precisely eliminated from somatic cells during early embryogenesis, resulting in chromosome fragmentation and the loss of key germline genes. The sites of elimination are strongly associated with conserved sequence motifs that likely direct DNA breakage. Comparative analyses indicate that PDE was present in the last common ancestor of Caenorhabditis and subsequently lost early during the evolution of many species, including C. elegans. The presence of PDE in the ancestors of one of biologys most important model organisms, together with recent discoveries in other eukaryotic lineages, reveals PDE to be a far more widespread and significant feature of evolution and development than previously recognised.

evolutionary biology↗

Comparative transcriptomics reveals an extracellular worm argonaute as an ancestral regulator of LTR retrotransposons.

Safeguarding the genome from non-self elements is essential for reproduction, development, and ageing. One of the major threats to genome integrity is Transposable Elements (TEs), which can be post-transcriptionally silenced through small RNAs (sRNAs) and argonaute proteins. Recent work suggests TE-derived sRNAs may also act as virulence factors in host-pathogen interactions. During infection, the intestinal parasite Heligmosomoides bakeri secretes a single argonaute protein (exWAGO) and a wide variety of TE-derived sRNAs. Although exWAGO is highly expressed, conserved, and secreted by parasitic nematodes, its function and sRNA guide preference remain unclear. Using comparative transcriptomics of the sRNAs bound to exWAGO within parasites of rodents, livestock and humans, and its orthologs in C. elegans, we found that exWAGO is capable of loading sRNAs produced from all classes of TEs in addition to some protein-coding and non-coding transcripts. However, our results suggest that the ancestral endogenous function of exWAGO was likely linked to LTR retrotransposon regulation. To understand how this relates to potential extracellular functions of exWAGO we also examined the sRNAs bound to exWAGO secreted by H. bakeri in both vesicular and non-vesicular forms. Extracellular exWAGO preferentially loads sRNA guides derived from non-autonomous and fragmented LTRs, suggesting the existence of adaptable reservoirs of regulatory sRNAs with potential roles in cross-species RNA communication. Together, our results show that exWAGO is part of an evolutionarily conserved pathway for LTR retrotransposon regulation, while preferentially utilising degenerated elements as sources of secreted sRNAs.

genomics↗

A Design-of-Experiments Strategy for Engineering 3D Topographical Features in Osteosarcoma Modelling

Osteosarcoma is a highly aggressive bone cancer with poor patient outcomes, partly due to the limited predictive power of current preclinical models. Conventional two-dimensional (2D) cultures fail to recapitulate physiologically relevant cell-matrix interactions, while animal models suffer from inter-species variability. To investigate how extracellular matrix (ECM) topographical features influence osteosarcoma behaviour, polylactic acid-based microparticles were engineered with bone-mimetic stiffness and defined surface topographies, guided by a Design-of-Experiments (DoE) approach. This enabled systematic variation of microparticle architecture (8-63 {micro}m diameter; 2-13 {micro}m dimple size) for studying the impact of surface topography on osteosarcoma cell behaviour in 3D culture, with doxorubicin treatment as a functional test to evaluate the effect of 3D topographical cues on chemotherapy sensitivity. Topography modulated cell-microparticle aggregation dynamics. At 96 hours post-seeding, MG-63 cells displayed significantly reduced metabolic activity on all 3D microparticle designs, with heterogeneously dimpled-topography cultures displaying significantly lower DNA content than conventional 2D cultures. In U2OS cells, metabolic activity was significantly lower on smooth microparticles compared to dimpled designs, with all 3D cultures showing significantly lower DNA content versus 2D. Response to doxorubicin was more strongly influenced by culture dimensionality than surface topography, underscoring the importance of 3D context. Significant metabolic differences between 3D and 2D cultures were observed, including the enrichment of amino acid related pathways and downregulation of ferroptosis signatures in 3D microparticle cultures. Topography displayed subtler effects on lipid and nucleotide metabolism. This study highlights how topographically-patterned 3D substrates can shape osteosarcoma cell behaviour and drug response for disease modelling applications. Our DoE-guided platform enables systematic investigation for dissecting how ECM-inspired physical cues influence osteosarcoma progression and therapeutic resistance. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/674028v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@42352aorg.highwire.dtl.DTLVardef@b066e4org.highwire.dtl.DTLVardef@13322e3org.highwire.dtl.DTLVardef@377d4a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Emergence and stabilisation of a neo-Y chromosome in nematode species with rare males

How do sex chromosomes evolve in the transition to asexuality? So far, species that depart from canonical sexual reproduction - for example, parthenogens with rare sex, or species where the paternal genome is set aside - have been found to carry either no sex chromosomes, or sex chromosomes but no male-specific sex chromosome (i. e., no Y). Here we reveal that, in Mesorhabditis nematodes, a new Y chromosome emerged once, from sexual ancestors, in species that have transitioned into an unconventional mode of reproduction called autopseudogamy. In this reproductive system, females produce clonal females plus rare ([~]10%) males that are needed for fertilisation, but that do not contribute to the female genome. Analysing the Y chromosomes of two autopseudogamous species, we found high levels of degeneration, most likely due to loss of recombination, and two additional conserved features: i) they accumulated male-beneficial genes, and ii) they display a strong fertilisation drive, in that mainly Y-bearing sperm fertilise female oocytes. Both features are likely evolutionarily favourable in the context of autopseudogamy. Our results suggest that male-specific chromosomes can still be maintained in systems with rare, and possibly genetically useless, males.

evolutionary biology↗

PhyloControl: a phylogeny visualisation platform for risk analysis in weed biological control

O_LIPhylogenetic distance is a key measure used to develop species lists for host specificity tests that delimit the fundamental and realised host range of candidate weed biocontrol agents to meet the assumptions of the centrifugal phylogenetic method. Plant pathogens and insects, even those with broad host ranges, exhibit some degree of phylogenetic conservatism in their host plant associations. Thorough host-specificity testing is crucial to minimise the risk of off-target damage by biocontrol agents to native and economically important plant species. To facilitate this, host test lists need to be developed from an understanding of evolutionary relationships, usually visualised as a phylogenetic tree generated from genetic data, together with plant functional traits and geospatial information. Currently, the process of obtaining a host test list is not standardised, and the manual steps are time-consuming and challenging. C_LIO_LIWe introduce a user-friendly visualisation tool called PhyloControl to aid researchers in their decision-making during biocontrol risk analysis. PhyloControl integrates taxonomic data, molecular data, spatial data, and plant traits in an intuitive interactive interface, empowering biocontrol practitioners to summarise, visualise and analyse data efficiently. C_LIO_LIComprehensively sampled phylogenetic trees are often unavailable, and older published phylogenies often lack branch resolution and support, which increases uncertainty. PhyloControl includes a workflow implemented through Quarto notebooks in R that allows users to download publicly available DNA sequences and perform phylogenetic analyses. The modular workflow also incorporates species distribution modelling to predict the current and potential extent of target weed species. C_LIO_LIPhyloControl will streamline the development of biocontrol host tests lists to support risk analysis and decision making in classical weed biological control. C_LI

plant biology↗

Genome evolution in parthenogenetic nematodes shaped by chromosome rearrangements and rare sex

In contrast to their dioecious relatives, members of the parthenogenetic Diploscapter nematode genus harbour their entire genome within a single pair of highly heterozygous chromosomes. To examine how this unusual karyotype relates to the evolution of parthenogenesis, we generated chromosome-level assemblies for two species in this clade: Diploscapter pachys and Diploscapter coronatus. Sequence comparisons revealed that the two genomes are colinear across their entirety, and that multiple ancestral chromosome fusions and extensive genomic rearrangements preceded the divergence of these two species. The presence of shortened telomeres and extended subtelomeric repeats suggests that the fusions arose from defects in telomere function in the lineage. Our analysis also identified an introgression event after divergence of the two species, suggesting that their parthenogenetic lifestyle may have been punctuated by rare sexual reproduction. These findings shed new light on how telomere loss, chromatin architecture, and reproductive strategies interconnect in shaping chromosome evolution.

genomics↗

Evolution of developmental bias explains divergent patterns of phenotypic evolution

Rates of phenotypic evolution vary across traits, and these evolutionary patterns themselves evolve. Understanding how development contributes--or biases--such patterns remains a challenge because it requires large-scale measurement of phenotypic variation resulting from random mutations across multiple species. Using the experimentally tractable system of nematode vulval development, we quantified the mutational sensitivity of six cell fates across two nematode clades. The results show that within each clade, mutational sensitivity is sufficient to explain the observed phenotypic evolution. The difference between clades can be explained by a simple spatial shift across cells of the sensitive region of a Wnt signaling dose-response curve. These findings underscore the importance of integrating the evolving genotype-phenotype map into the understanding of phenotypic change at both micro- and macroevolutionary scales.

evolutionary biology↗

Teaching transposon classification as a means to crowd source the curation of repeat annotation - a tardigrade perspective

The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. However, manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd sourcing efforts could offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Here, we present an example of such crowd sourcing effort developed through both in-person and online courses built around a collaborative peer-reviewed teaching process that can be used as teaching reference guide for similar projects. The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs: A hidden treasure awaits discovery within non-model organisms.

evolutionary biology↗

Revisiting Hox gene evolution and Hox clusterlinkage across Nematoda

Hox genes are central to metazoan body plan formation, patterning and evolution, playing a critical role in cell fate decisions early in embryonic development in invertebrates and vertebrates. While the archetypical Hox gene cluster consists of members of nine ortholog groups (HOX1-HOX9), arrayed in close linkage in the order in which they have their anterior-posterior patterning effects, nematode Hox gene sets do not fit this model. The Caenorhabditis elegans Hox gene set is not clustered and contains only six Hox genes from four of the ancestral groups. The pattern observed in C. elegans is not typical of the phylum, and variation in orthologue set presence and absence and in genomic organisation has been reported. Recent advances in genome sequencing have resulted in the availability of many novel genome assemblies in Nematoda, especially from taxonomic groups that had not been analysed previously. Here, we explored Hox gene complements in high-quality genomes of 80 species from all major clades of Nematoda to understand the evolution of this key set of body pattern genes and especially to probe the origins of the "dispersed" cluster observed in C. elegans. We also included the recently available high-quality genomes of some Nematomorpha as an outgroup. We find that nematodes can have Hox genes from up to six orthology groups. While nematode Hox "clusters" are often interrupted by unrelated genes we identify species in which the cluster is intact and not dispersed.

developmental biology↗