Biology subjects

Loschko, T.

Publications and source records attributed to Loschko, T..

6 recordsLinked to original sources

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↗

bioRxiv2024

Interspecies systems biology links bacterial metabolic pathways to nematode gene expression, behavior, and survival

All animals live in tight association with complex microbial communities, yet studying the effects of individual bacteria remains challenging. Here, we exploit the system of the bacterial feeding nematode Pristionchus pacificus, where specific interactions can be studied in isolation. We sequenced the genomes of 84 Pristionchus-associated bacteria to investigate how differences in bacterial metabolic potential affect nematode traits. Specifically, we identified the Paerucumarin biosynthesis pathway as a strong candidate for nematode survival. Hypothesizing that bacterial production of coumarin derivatives contributed to increased lethality, we demonstrated nematicidal effects of two related compounds using supplementation assays. To explore metabolic interactions at a broader scale, we generated nematode transcriptomes for 38 bacterial diets and constructed a coexpression network that revealed distinct developmental and environmental signatures. Interspecies association studies resulted in a bipartite network with more than 2,800 interactions which may assist future studies to identify metabolites affecting various biological processes.

microbiology↗

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↗

bioRxiv2023

Halophilic nematodes live in America's Dead Sea

Extremophiles can reveal the origins of life on Earth and the possibility of life elsewhere. Most identified extremophiles are single-cell microbes, leaving gaps in our knowledge concerning the origins and habitable limits of multicellular organisms. Here, we report the recovery of roundworms (Phylum Nematoda) from the Great Salt Lake (GSL), UT, a hypersaline lake referred to as "Americas Dead Sea". Nematodes were found primarily in microbialites, benthic organosedimentary structures once abundant on early Earth. 16S sequencing of individual nematodes revealed a diverse bacterial community distinct from its surrounding habitat. Phylogenetic divergence compared to Owens Lake, another terminal lake in the Great Basin, suggests that GSL nematodes represent multiple previously undescribed species. These findings update our understanding of halophile ecosystems and the habitable limit of animals. One-Sentence SummaryWe report the discovery of novel halophilic nematodes in microbialites of the Great Salt Lake, UT.

ecology↗

bioRxiv2022

Histone 4 lysine 5/12 acetylation provides a plasticity code with epigenetic memory of environmental exposure

Development can be altered to match phenotypes with the environment, and the genetic mechanisms that direct such alternative phenotypes are beginning to be elucidated1,2. Yet, the rules that govern environmental sensitivity vs. invariant development (canalization), and potential epigenetic memory, remain unknown. Here, we show that plasticity of nematode mouth forms is determined by histone 4 lysine 5 and 12 acetylation (H4K5/12ac). Acetylation in early larval stages provides a permissive chromatin state at specific switch genes, which is susceptible to induction during the critical window of environmental sensitivity. As development proceeds deacetylation shuts off switch gene expression to end the critical period. We show that inhibiting deacetylase enzymes leads to long-term epigenetic memory, demonstrating that histone modifications in juveniles can carry environmental information to affect organismal traits in adults. This epigenetic regulation of plasticity appears to be derived from an ancient mechanism of licensing developmental speed that is conserved between flies and nematodes. Thus, H4K5/12ac provides a histone plasticity code with epigenetic potential that can be stored and erased by acetylation and deacetylation, respectively. HighlightsO_LIReciprocal transplant experiments reveal a critical time window of mouth-form plasticity. C_LIO_LIEntry and exit of the critical window is determined by H4K5/12ac at the switch gene eud-1. C_LIO_LIH4K12ac maintains transcriptional competence by supporting elongation. C_LIO_LIInhibition of deacetylation freezes an initial developmental trajectory, resulting in long-term epigenetic memory. C_LIO_LIH4K5/12 acetylation control of plasticity was co-opted from an ancestral role in controlling developmental speed. C_LI

developmental biology↗

bioRxiv2020

Comparative genomics and community curation further improve gene annotations in the nematode Pristionchus pacificus

BackgroundNematode model organisms such as Caenorhabditis elegans and Pristionchus pacificus are powerful systems for studying the evolution of gene function at a mechanistic level. However, the identification of P. pacificus orthologs of candidate genes known from C. elegans is complicated by the discrepancy in the quality of gene annotations, a common problem in nematode and invertebrate genomics. ResultsHere, we combine comparative genomic screens for suspicious gene models with community-based curation to further improve the quality of gene annotations in P. pacificus. We extend previous curations of one-to-one orthologs to larger gene families and also orphan genes. Cross-species comparisons of protein lengths and screens for atypical domain combinations and species-specific orphan genes resulted in 4,221 candidate genes that were subject to community-based curation. Corrections for 2,851 gene models were implemented in a new version of the P. pacificus gene annotations. The new set of gene annotations contains 28,896 genes and has a single copy ortholog completeness level of 97.6%. ConclusionsOur work demonstrates the effectiveness of comparative genomic screens to identify suspicious gene models and the scalability of community-based approaches to improve the quality of thousands of gene models. Similar community-based approaches can help to improve the quality of gene annotations in other invertebrate species, including parasitic nematodes.

genomics↗