Biology subjects

Berger, D.

Publications and source records attributed to Berger, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Cellular context restricts a promiscuous m6A reader IDR to a single functional effector interface for mRNA decay

N6-methyladenosine (m6A) is a conserved mRNA modification that regulates transcript stability, yet how m6A readers engage effectors remains unknown. We show that during yeast meiosis, the YTH-domain protein Pho92 promotes the decay of m6A-modified transcripts through an uncharacterised, promiscuous intrinsically disordered region (IDR). In vitro, the Pho92 IDR makes multiple contacts with the Ccr4-NOT deadenylase complex and drives tethered reporter decay in the absence of any single subunit. Yet in meiosis, turnover of endogenous m6A-modified transcripts strictly depends on a single interface: direct binding of the Pho92 IDR to Caf40. A single hydrophobic residue substitution is sufficient to abolish Caf40 binding and halt transcript decay. Human YTHDF proteins can functionally substitute for Pho92, but require multiple hydrophobic patches within the IDR for decay activity. Thus, on endogenous m6A-modified transcripts during meiosis, the promiscuous Pho92 IDR is restricted to a single functional interface, revealing unappreciated specificity in m6A-directed mRNA decay.

molecular biology↗

bioRxiv2026

The mode and repeatability of thermal adaptation in gene expression in the seed beetle Callosobruchus maculatus

Transcriptional plasticity can maintain organismal homeostasis but its potential to buffer negative effects from climate change remains contentious and may rely on genetic adaptation. Theory predicts two general outcomes: genetic reinforcement, where adaptive plasticity is enhanced by genetic adaptation; or genetic compensation, where genetic adaptation reverses maladaptive plasticity. Here, we explored the prevalence, repeatability, and molecular basis of compensation and reinforcement of gene expression responses to temperature using experimental evolution in the beetle pest, Callosobruchus maculatus. We evolved lines from three genetic backgrounds under hot or cold conditions and compared them to ancestral lines after 80-135 generations. Cold adaptation was dominated by genetic compensation, revealing a highly repeatable mode of adaptation across backgrounds, however, the underlying genes and their biological functions were largely idiosyncratic. In contrast, heat adaptation showed a less consistent mode, combining compensation and reinforcement, but greater repeatability at the level of genes and their functions. Network analysis identified many heat reinforcement genes as hubs and strongly temperature dependent, suggestive of roles in orchestrated adaptive thermal plasticity, potentially explaining their high repeatability. Genomic analyses identified repeatable allele frequency changes at both hot and cold compensation and reinforcement genes during experimental evolution. However, these were not causally linked to changes in expression levels, suggesting trans-regulation. There was also no broader correspondence between the level of repeatability of sequence and expression evolution across gene categories. Our findings suggest that the predictability of evolution under climate change might critically depend on the thermal range and the level of the genotype-phenotype map that is studied.

evolutionary biology↗

bioRxiv2026

Pest evolution amplifies projected crop losses under climate change

Climate change influences the physiology and population dynamics of ectothermic pests, with major repercussions for global crop production. Yet, how evolution modulates these outcomes remains unclear. We exposed the widespread beetle pest Callosobruchus maculatus to 10 years of experimental evolution at different temperatures and quantified thermal responses of life-history traits. Hot- and cold-adapted populations evolved differences in thermal sensitivity, but these were modest relative to evolved differences in trait averages. By leveraging high-resolution temperature time-series we show that the observed evolution translates into cold-adapted genotypes having highest fitness in cold climates and hot-adapted genotypes in warm climates. Hot-adapted beetles maximize fitness in warm climates by increased larval growth, resulting in larger body sizes and higher fecundity. This evolutionary strategy compounds projected crop losses under warming by increasing both intrinsic population growth and per-capita host consumption rates. By year 2100 under intermediate-to-high warming (SSP3-7.0), pest evolution is projected to increase global crop damage potential by +113% from present--twice that expected from warming alone (not accounting for evolution). In major crop-producing areas, where temperatures and the beetles host consumption rates are already high, warming increases average crop damage potential by +29%, but evolution amplifies this three-fold to +87%. Evolution also expands C. maculatus projected colonizable range and in some regions even flips forecasted crop damage reductions into increases. These results identify climate-driven evolution of pest life-histories as an amplifier of agricultural losses and suggest that current projections may significantly understate the threat warming poses to future food security.

ecology↗

bioRxiv2026

RAEM: random-access electron microscopy for revisitable 3D imaging

Volume electron microscopy is essential for understanding cells, tissues, and neural circuits in their native 3D context, but many biological specimens are too large to image exhaustively at nanometer resolution. Researchers therefore must choose between broad anatomical context and ultrastructural detail. We introduce random-access electron microscopy (RAEM), a framework for studying fixed tissue repeatedly across scales rather than imaging it once at a single resolution. RAEM first builds a lower resolution 3D survey of the specimen, then uses accumulated human or AI-derived knowledge of that volume to guide the microscope back to selected physical sites for high resolution imaging. By linking reconstructed 3D coordinates to precise electron-beam positions on the original sections, RAEM enables targeted imaging of membranes, vesicles, and other nanoscale structures within specimens that would be impractical to image exhaustively. We demonstrate RAEM with vesicle-resolved imaging of synaptic boutons in human cortex, targeted imaging of more than one million human cortical mitochondria, hierarchical imaging of a nematode nervous system, and retrospective targeting of a previously published petabyte-scale human cortical volume. RAEM turns serial-section EM into a query-driven, multi-resolution approach for scalable biomedical discovery.

neuroscience↗

bioRxiv2026

The flaws of fitness functions in changing environments

When predicting species responses to changing environments, one can use mathematical functions that describe how individual fitness components depend on the environment, or a single "composite" function that directly links fitness to the environmental state. The former approach is a cornerstone of process-based modelling, but the latter remains standard for developing fundamental theory and making ecological predictions. Yet, fitness is not a single instantaneous trait, but an integrated outcome of multiple underlying processes accruing throughout an organisms life. We show that by ignoring the distinct environmental dependence of the underlying processes, predictions from composite fitness functions become inherently flawed in variable environments. We explore the magnitude of this error by leveraging empirical thermal reaction norms for four important life-history processes in an insect pest, the seed beetle Callosobruchus maculatus. We parameterize two fitness functions: one explicitly modelling the temperature-dependence of the four life-history traits independently (the "ground truth") and one composite function, which treats fitness as a single, instantaneous outcome of the environment. By combining these two functions with hourly temperature data, we projected demographic responses under different warming scenarios across 300 sites over three beetle population origins (California, USA; Yemen; Brazil). We show that the composite function over- or underestimates fitness depending on subtle climatic differences and whether fitness is assumed to accumulate additively or multiplicatively, highlighting the problems of applying composite fitness functions to variable conditions. We conclude that explicitly modeling trait-specific processes will become increasingly important for accurate eco-evolutionary forecasting under future environmental change.

ecology↗

bioRxiv2026

Are Synaptic Clefts Directionally Oriented?

Synapses are fundamental building blocks of cortical circuits, yet their geometry is typically regarded as a local property, independent of mesoscale architecture. The prevailing assumption is that synaptic clefts are isotropically oriented in space. Here, we test this assumption by analyzing approximately 117 million synaptic clefts from two independent 1 mm3 electron microscopy datasets: the human H01 middle temporal gyrus and the mouse MICrONS primary visual cortex, using three independent cleft-extraction methods. Across both volumes, we observe that synaptic cleft orientations are not randomly distributed, but instead show statistically significant and spatially coherent directional biases across cortical layers. This mesoscale anisotropy is conserved across species, yet is stronger and more consistent in human association cortex than in mouse sensory cortex, a difference that may reflect the expanded dendritic arbors and greater integrative demands of human pyramidal neurons. We propose that cleft orientation bias is a geometric consequence of the axonal and dendritic architecture that shapes synapse formation, representing a new candidate organizational feature of cortical microarchitecture with potential implications for circuit computation and neuromodulation. These findings motivate targeted physiological studies to determine whether synaptic orientation contributes causally to cortical function.

neuroscience↗

bioRxiv2025

The aging transcriptome: a condition-dependent response to a deteriorating soma

Organismal function requires precise gene expression, as deviations reduce fitness and can cause disease. The widespread expression changes characteristic of old age therefore suggests that aging itself may partly stem from gene dysregulation. Alternatively, many of these changes may represent a plastic response to somatic decline, tuning the organism to an altered physiological state. We tested the latter hypothesis by experimentally reducing the condition of Drosophila melanogaster females independently of age and comparing the resulting expression changes with those occurring naturally during aging. Consistent with the plasticity hypothesis, we find substantial overlap between genes responding to reduced condition and old age. Downregulated genes are enriched for metabolic functions, with a consistent, albeit weaker, association with mitochondrial function and cytoplasmic translation, while upregulated genes relate to genome maintenance. Both old age and reduced condition also cause downregulation of tissue-specific and female-biased genes, as expected when energy is reallocated to core cellular processes. In line with a coordinated transcriptional response to old age, both down- and upregulated genes within enriched functional categories show reduced expression variability and experience strong purifying selection. Collectively, our results support that the aging soma elicits a plastic transcriptional program that adjusts the organism to a declining physiological condition, implying that many age-related expression changes mitigate rather than accelerate somatic aging. These findings call for a more nuanced view of the causes and consequences of age-related transcriptional change, with implications for both theoretical and applied research on aging and disease.

genetics↗

bioRxiv2025

Environmental predictability favours adaptive behavioural plasticity and relaxes selection against deleterious alleles

Behavioural plasticity can play a key role in evolution by either facilitating or impeding genetic adaptation. The latter occurs when behaviours mitigate selection pressures that otherwise would target associated traits. Therefore, environments that facilitate adaptive behavioural plasticity could relax the strength of natural selection, but experimental evidence for this prediction remains scarce. Here, we first demonstrate that maternal care in the beetle Callosobruchus maculatus is dependent on environmental cues that allow females to reduce larval competition via learning and informed oviposition choices. We show that this facilitation of maternal care relaxes selection against deleterious alleles in offspring. We further find that mothers of low genetic quality generally provide poorer care. However, when receiving environmental cues providing accurate information about future host-quality, the increased opportunity for adaptive behavioural plasticity reduced genetic differences in maternal care, further relaxing selection against deleterious alleles. We use our data to illustrate how the identified link between adaptive behavioural plasticity in maternal care and the strength of natural selection can impact indirect genetic effects between mothers and offspring and the accumulation of cryptic genetic loads in populations inhabiting environments that differ in their predictability.

animal behavior and cognition↗

bioRxiv2025

Life history evolution of insects in response to climate variation: seasonal timing versus thermal physiology

Climate adaptation in insects can proceed via responses in life history traits and their thermal plasticity, and through phenological shifts mediated by responses to photoperiodic cues ("photoperiodism"). While, experimental studies demonstrate evolutionary potential for both modes of adaptation, it remains unclear how evolution will unfold in natural populations, limiting our ability to predict how insects will respond to climate change. Here we review the literature and perform an analysis of published studies revealing that photoperiodism for diapause induction evolves predictably along latitude, with high-latitude populations entering diapause earlier. In contrast, although a few species showed clinal variation in life history and thermal plasticity, the direction of these clines were not consistent across taxa. This suggests that while insect life history and physiological adaptation to temperature can evolve, phenological shifts via evolution of photoperiodism is likely to be a more common and predictable response to future climate change.

ecology↗

bioRxiv2024

Strong Selection, but low repeatability: Temperature-specific effects on genomic predictions of adaptation

Climate warming is threatening biodiversity by increasing temperatures beyond the optima of many ectotherms. Due to the inherent non-linear relationship between temperature and the rate of cellular processes, such shifts towards hot temperature are predicted to impose stronger selection compared to corresponding shifts toward cold temperature. This suggests that when adaptation to warming occurs, it should be relatively rapid and predictable. Here, we tested this hypothesis from the level of single-nucleotide polymorphisms to life-history traits, by conducting an evolve-and-resequence experiment on three genetic backgrounds of the beetle, Callosobruchus maculatus. Indeed, phenotypic evolution was faster and more repeatable at hot, relative to cold, temperature. However, at the genomic level, adaptation to heat was less repeatable when compared across genetic backgrounds. As a result, genomic predictions of phenotypic adaptation in populations exposed to hot temperature were accurate within, but not between, backgrounds. These results seem best explained by genetic redundancy and an increased importance of epistasis during adaptation to heat, and imply that the same mechanisms that exert strong selection and increase repeatability of phenotypic evolution at hot temperature, reduce repeatability at the genomic level. Thus, predictions of adaptation in key phenotypes from genomic data may become increasingly difficult as climates warm.

evolutionary biology↗

bioRxiv2024

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goat farming in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, n = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identified key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control. AUTHOR SUMMARYUnderstanding the genetics of anthelmintic resistance is a critical part of the sustainable control of parasitic worms. Here, we have generated a chromosome-scale genome assembly for the gastrointestinal nematode, Teladorsagia circumcincta, one of the most important pathogens of sheep in temperate climates worldwide. This genome and its annotation offers a substantial improvement over existing genetic resources, and will enable new insight into the biology for this parasite and new opportunities to characterise therapeutic targets such as drug and vaccine candidates. We used this resource to map genetic variation associated with resistance to multiple anthelmintic drug classes used as the primary means of parasite control, confirming known candidate genes and variants (i.e., beta-tubulin isotypes 1 and 2 associated with benzimidazole resistance, and acr-8 associated with levamisole resistance, and pgp-9 copy number variation, of which overexpression is associated broadly with anthelmintic resistance) and revealing new regions of the genome associated with drug treatment responses (i.e. 34-38 Mb on chromosome 5 associated with ivermectin resistance). Our results highlight the importance of a contiguous genome assembly and the use of complementary experimental approaches to reveal the impact of drug-mediated selection, both historically and directly in response to treatment, on genome-wide genetic variation.

genomics↗

bioRxiv2024

Life-history adaptation under climate warming magnifies the agricultural footprint of a cosmopolitan insect pest

Climate change is affecting population growth rates of ectothermic pests with potentially dire consequences for agriculture, but how rapid genetic adaptation impacts these dynamics remains unclear. To address this challenge, we predicted how climate change adaptation in life-history traits of insect pests may affect future agricultural yields by unifying thermodynamics based on first principles with classic life-history theory. Our model predicts that warming temperatures favour changes in resource allocation decisions coupled with increased larval host consumption, resulting in a predicted double-blow on agricultural yields under future climate change. We find support for these predictions by studying thermal adaptation in life-history traits and underlying gene expression in the wide-spread insect pest, Callosobruchus maculatus, with five years of life-history evolution under experimental warming causing an almost two-fold increase in its predicted agricultural footprint. These results emphasize the need for integrating a mechanistic understanding of life-history evolution into forecasts of pest impact.

ecology↗

bioRxiv2023

Coevolution of longevity and female care of male gametes

An often-overlooked aspect of life-history optimization is the allocation of resources to protect the germline and secure safe transmission of genetic information. While failure to do so renders significant fitness consequences in future generations, germline maintenance comes with substantial costs. Thus, germline allocation should trade-off with other life history decisions and be optimized in accordance with an organisms reproductive schedule. Here we tested this hypothesis by studying germline maintenance in lines of seed beetle, selected for early (E) or late (L) reproduction for 350 and 240 generations, respectively. Female animals provide maintenance and screening of male gametes in their reproductive tract and oocytes. Here, we revealed the ability of young and aged E and L-females to provide this form of germline maintenance by mating them to males with ejaculates with artificially elevated levels of protein and DNA damage. We find that germline maintenance in E-females peaks at young age and then declines, while the opposite is true for L-females, in accordance with the age of reproduction in respective regime. These findings identify the central role of allocation to secure germline integrity in life history evolution and highlight how females can play a crucial role in mitigating effects of male germline decisions on mutation rate and offspring quality.

evolutionary biology↗

bioRxiv2023

Multiplexed Volumetric CLEM enabled by antibody derivatives provides new insights into the cytology of the mouse cerebellar cortex

Mapping neuronal networks that underlie behavior has become a central focus in neuroscience. While serial section electron microscopy (ssEM) can reveal the fine structure of neuronal networks (connectomics), it does not provide the molecular information that helps identify cell types or their functional properties. Volumetric correlated light and electron microscopy (vCLEM) combines ssEM and volumetric fluorescence microscopy to incorporate molecular labeling into ssEM datasets. We developed an approach that uses small fluorescent single-chain variable fragment (scFv) immuno-probes to perform multiplexed detergent-free immuno-labeling and ssEM on the same samples. We generated eight such fluorescent scFvs that targeted useful markers for brain studies (green fluorescent protein, glial fibrillary acidic protein, calbindin, parvalbumin, voltage-gated potassium channel subfamily A member 2, vesicular glutamate transporter 1, postsynaptic density protein 95, and neuropeptide Y). To test the vCLEM approach, six different fluorescent probes were imaged in a sample of the cortex of a cerebellar lobule (Crus 1), using confocal microscopy with spectral unmixing, followed by ssEM imaging of the same sample. The results show excellent ultrastructure with superimposition of the multiple fluorescence channels. Using this approach we could document a poorly described cell type in the cerebellum, two types of mossy fiber terminals, and the subcellular localization of one type of ion channel. Because scFvs can be derived from existing monoclonal antibodies, hundreds of such probes can be generated to enable molecular overlays for connectomic studies.

neuroscience↗

bioRxiv2022

Heat stress reveals a fertility debt owing to postcopulatory sexual selection

Climates are changing rapidly, demanding equally rapid adaptation of natural populations. Whether sexual selection can aid such adaptation is under debate; while sexual selection should promote adaptation when individuals with high mating success are also best adapted to their local surroundings, the expression of sexually selected traits can incur costs. Here we asked what the demographic consequences of such costs may be once climates change to become harsher and the strength of natural selection increases. We investigated how an evolutionary history of strong postcopulatory sexual selection (sperm competition) affects male fertility under acute adult heat stress. Harnessing the empirical potential of long-term experimental evolution in the seed beetle Callosobruchus maculatus, we assessed the thermal sensitivity of fertility (TSF) in replicated lines maintained for 68 generations under three alternative mating regimes manipulating the opportunity for sexual and natural selection. We find that males evolving under strong sexual selection suffer from increased TSF, and that male success in sperm competition (P2: sperm offense) is genetically correlated to increased TSF. Interestingly, females from the regime under strong sexual selection, who experienced relaxed selection on their own reproductive effort, had high fertility in benign settings but suffered increased TSF, like their brothers. This implies that female fertility and TSF evolved through genetic correlation with reproductive traits sexually selected in males. Paternal but not maternal heat stress reduced offspring fertility with no evidence for adaptive transgenerational plasticity among heat-exposed offspring, indicating that the observed effects may compound over generations. Our results suggest that trade-offs between fertility and traits increasing success in postcopulatory sexual selection can be revealed in harsh environments. This can put polyandrous species under increased risk during extreme heat waves expected under future climate change. IMPACT STATEMENTHow will populations respond to a warming world? Of increasing concern are negative effects of elevated temperatures on fertility, which in many species are observed for temperatures substantially lower than the ones causing death. Incorporating knowledge on species-specific thermal fertility limits has improved estimates of current species ranges but renders a more pessimistic view of the potential for adaptive responses under climate change. Sexual selection is a process that can interact with thermal sensitivity of fertility and is strongest in males of polyandrous species, in which females mate multiply and sperm of multiple males compete for fertilization of female eggs. Therefore, males of polyandrous species often invest heavily in sperm competition. However, given finite resources, increased investment in sperm competition can come at an expense of other processes needed to maintain the integrity of the male germline, which when compromised can reduce fertility and offspring quality. How may such male investment, fuelled by sexual selection, affect species responses to climate warming? To address this question, we first evolved populations under different laboratory settings that independently manipulated the levels of natural and sexual selection. We exposed adults from these populations to acute heat stress and measured the fertility of males and females. We find that sexual selection on males leads to a fertility debt that is revealed under heat stress. This debt was also apparent in females, who themselves were not selected for increased reproductive investment. Thus, genes under sexual selection in males seems to have impaired fertility in both sexes under heat stress. Forecasts of species response to climate change that do not incorporate thermal fertility limits and sexual selection may therefore underestimate species vulnerability to increasing temperatures.

evolutionary biology↗

bioRxiv2022

Increased male investment in sperm competition results in offspring of lower quality

Male animals often show higher mutation rates than their female conspecifics. A hypothesis for this male-bias is that competition over fertilization of female gametes leads to increased male investment into reproduction at the expense of maintenance and repair, resulting in a trade-off between male success in sperm competition and offspring quality. Here, we provide evidence for this hypothesis by harnessing the power of experimental evolution to study effects of sexual selection on the male germline in the seed beetle Callosobruchus maculatus. We first show that 50 generations of evolution under strong sexual selection, coupled with experimental removal of natural selection resulted in males that are more successful in sperm competition. We then show that these males produce progeny of lower quality if engaging in socio-sexual interactions prior to being challenged to surveil and repair experimentally induced damage in their germline, and that the presence of male competitors alone can be enough to elicit this response. We identify 18 candidate genes that showed differential expression in response to the induced germline damage, with several of these previously implicated in processes associated with DNA repair and cellular maintenance. These genes also showed significant expression changes across socio-sexual treatments of fathers and predicted the reduction in quality of their offspring, with expression of one gene also being strongly correlated to male sperm competition success. Sex differences in expression of the same 18 genes indicate a substantially higher female investment in germline maintenance. While more work is needed to detail the exact molecular underpinnings of our results, our findings provide rare experimental evidence for a trade-off between male success in sperm competition and germline maintenance. This suggests that sex-differences in the relative strengths of sexual and natural selection are causally linked to male mutation bias. The tenet advocated here, that the choices of an individual can affect plasticity of its germline and the resulting genetic quality of subsequent generations, has several interesting implications for mate choice processes.

evolutionary biology↗

bioRxiv2022

Genome-wide analysis of Schistosoma mansoni reveals population structure and praziquantel drug selection pressure within Ugandan hot-spot communities

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment. Author summarySchistosomiasis is caused by parasitic helminths of the genus Schistosoma. Schistosoma mansoni is the primary cause of intestinal schistosomiasis, a devastating and widespread parasitic infection that causes morbidity, death and socio-economic impact on endemic communities across the world and especially sub-Saharan Africa. Using whole-genome sequencing, we were able to elucidate the parasite population within Lake Victoria island fishing communities in Uganda which are among the major hotspots for schistosomiasis. We further assessed genetic markers that might be linked to recent observations concerning reduced susceptibility to praziquantel, the major drug used in the treatment of this disease. Whole-genome data on the population genetics of S. mansoni in an African setting will provide a strong basis for future functional genomics or transcriptomic studies that will be key to identifying drug targets, improving existing drugs or developing new therapeutic interventions.

genomics↗

bioRxiv2022

Post-embryonic maturation of the C. elegans motor circuit

During development, animals can maintain behavioral output even as the underlying circuits structurally remodel. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse re-wiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without disrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed: 1) Embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring; 2) Post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords; 3) Embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons; 4) This transition is repeated region by region along the body in an anterior to posterior sequence, following the birth order of post-embryonic neurons. Through this orchestrated, programmed and gradual rewiring, the motor circuit transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration. HighlightsO_LIPost-embryonic motor circuit maturation was reconstructed by synapse-resolution serial EM. C_LIO_LIMotor patterns are maintained as the circuit matures from asymmetric to symmetric configuration. C_LIO_LIProgrammed rewiring gradually and sequentially transforms the circuit structure. C_LIO_LIPreparatory and communicative wiring-rewiring allows maturation without functional disruption. C_LI

neuroscience↗