Biology subjects

Park, H.

Publications and source records attributed to Park, H..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

Endocytic BDNF secretion through extracellular vesicle-dependent secretory pathways in astrocytes

Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating diverse neuronal functions in an activity-dependent manner. Although BDNF is synthesized primarily in neurons, astrocytes can also supply BDNF through various routes, including the recycling of neuron-derived BDNF. Despite accumulating evidence for astrocytic BDNF uptake and resecretion of neuronal BDNF, the detailed mechanisms underlying astrocytic BDNF recycling remain unclear. Here, we report that astrocytic resecretion of endocytosed BDNF is mediated by an extracellular vesicle (EV)-dependent secretory pathway. In cultured primary astrocytes, extracellular BDNF was endocytosed into CD63-positive EVs, and stimulation of astrocytes with ATP could evoke the release of endocytosed BDNF from CD63-positive vesicles. Downregulation of vesicle-associated membrane protein 3 (Vamp3) led to an increase in the colocalization of endosomal BDNF and CD63 but a decrease in extracellular vesicle release, suggesting the necessity of Vamp3-dependent signaling for EV-mediated BDNF secretion. Collectively, our findings demonstrate that astrocytic recycling of neuronal BDNF is dependent on the EV-mediated secretory pathway via Vamp3-associated signaling.

neuroscience↗

bioRxiv2024

Serpina1e mediates the exercise-induced enhancement of hippocampal memory

The exercise-induced enhancement of learning and memory is thought to be regulated by body{square}brain interactions via secretory proteins in the blood plasma1,2. Given the prominent role that skeletal muscle plays during exercise, the beneficial effects of exercise on cognitive functions appear to be mediated by muscle-derived secretory factors including myokines3,4. However, the specific myokines that exert beneficial effects on cognitive functions remain to be elucidated. Here, we reveal that a novel myokine, Serpina1e, acts a molecular mediator that directly supports long-term memory formation in the hippocampus. Using an in vivo myokine-labeling mouse model, proteomic analysis revealed that the Serpina1 family of proteins are the myokines whose levels increased the most in plasma after chronic aerobic exercise for 4 weeks. Systemic delivery of recombinant Serpina1e into sedentary mice was sufficient for reproducing the beneficial effect of exercise on hippocampus-associated cognitive functions. Moreover, plasma Serpina1e can cross the blood-cerebral spinal fluid (CSF) barrier and blood-brain barrier to reach the brain, thereby influencing hippocampal function. Indeed, an increase in the plasma level of Serpina1e promoted hippocampal neurogenesis, increased the levels of brain-derived neurotrophic factor (BDNF) and induced neurite growth. Our findings reveal that Serpina1e is a myokine that migrates to the brain and mediates exercise-induced memory enhancement by triggering neurotrophic growth signaling in the hippocampus. This discovery elucidates the molecular mechanisms underlying the beneficial effects of exercise on cognitive function and may have implications for the development of novel therapeutic interventions for alleviating cognitive disorders.

neuroscience↗

bioRxiv2024

Gut microbiome shifts in chronic systolic heart failure are associated with disease severity and clinical improvement

Chronic systolic heart failure (HF) is a prevalent and morbid disease with marked variability in its progression and response to therapies. The gut microbiome may play a role in pathophysiology and progression of chronic HF, but clinical studies investigating relationships between the two are lacking. We analyzed the gut microbiome in a cohort of adults with chronic systolic HF caused by non-ischemic cardiomyopathy (n=59) using multi-omics profiling and, in some cases, longitudinal sampling. We identified microbiome differences compared to healthy subjects (n=50) and associated these differences with host metabolites, inflammatory markers and physiology. We found depletion of the anti-inflammatory probiotic Bifidobacterium and the associated short chain fatty acid producing and formaldehyde detoxifying pathways in the chronic HF cohort. We also discovered HF-specific microbiome-host immunome interactions. In addition to identifying several taxa and microbial pathways broadly associated with HF disease severity, we found significant links between Bifidobacterium and clinical HF improvement over time. Gut microbiome-host multi-omic data integration revealed a close association between Bifidobacterium and circulating metabolites previously implicated in cardiovascular physiology (e.g., malonic acid), thus pointing to potential mechanisms through which Bifidobacterium may affect chronic HF physiology. Our results suggest that Bifidobacterium may serve as a biomarker for chronic HF trajectory as well as suggest potential novel therapeutic interventions strategies.

microbiology↗

bioRxiv2024

Decoding RNA Metabolism by RNA-linked CRISPR Screening in Human Cells

RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC screens highlight modular interactions between gene networks regulating splicing, translation, and decay of mRNAs. When combined with biochemical fractionation of polysomes, ReLiC reveals striking pathway-specific coupling between growth fitness and mRNA translation. Perturbing different components of the translation and proteostasis machineries have distinct effects on ribosome occupancy, while perturbing mRNA transcription leaves ribosome occupancy largely intact. Isoform-selective ReLiC screens capture differential regulation of intron retention and exon skipping by SF3b complex subunits. Chemogenomic screens using ReLiC decipher translational regulators upstream of mRNA decay and uncover a role for the ribosome collision sensor GCN1 during treatment with the anti-leukemic drug homoharringtonine. Our work demonstrates ReLiC as a versatile platform for discovering and dissecting regulatory principles of human RNA metabolism.

molecular biology↗

bioRxiv2024

Confirmation Bias through Selective Use of Evidence in Human Cortex

Decision-makers often process new evidence selectively, depending on their current beliefs about the world. We asked whether such confirmation biases result from biases in the encoding of sensory evidence in the brain, or alternatively in the utilization of encoded evidence for behavior. Human participants estimated the source of a sequence of visual-spatial evidence samples while we measured cortical population activity with magnetoencephalography. Halfway through the sequence, participants were prompted to judge the more likely source category. We find that processing of subsequent evidence depends on its consistency with the previously chosen category. Evidence encoded in parietal cortex contributes more to the estimation report when that evidence is consistent with the previous choice compared to when it contradicts that choice. Our results indicate that information contradicting pre-existing beliefs has little impact on subsequent behavior, despite being precisely encoded in the brain. This provides room for deliberative control to counteract confirmation biases.

neuroscience↗

bioRxiv2024

Unveiling the Power of PROTAC Valency: Navigating Cell Type-Specific Hook Effects

Targeted protein degradation (TPD) using bivalent proteolysis-targeting chimeras (PROTAC) technology has shown potential in expanding the "druggable" proteome. In their publication in Nature Chemical Biology, Imaide et al.1 posited that augmenting PROTAC valency could potentially lead to the formation of long-lived ternary complexes between PROTAC, the protein of interest (POI), and E3 ligase, thereby constraining the formation of potent binary complexes, as evidenced by a pronounced hook effect. The authors introduced SIM1, a trivalent von Hippel-Lindau (VHL)-based PROTAC, which exhibited a superior degradation profile in comparison to its parent molecule MZ1, towards bromo and extra terminal (BET) proteins, with a predilection for BRD2. The authors attributed this heightened degradation capability of SIM1 over bivalent MZ1 as supportive evidence for their hypothesis. While we concur with the notion that increasing valency and avidity could enhance the efficacy of a PROTAC, the claim that trivalent PROTACs unequivocally eliminate the hook effect is not entirely accurate. We propose that the presence or absence of a hook effect is influenced by numerous factors beyond PROTAC valency.

cancer biology↗

bioRxiv2024

Bilateral integration in somatosensory cortex is controlled by behavioral relevance

Sensory perception naturally requires processing stimuli from both sides of the body. Yet, how neurons bind stimulus features across the hemispheres to create a unified perceptual experience remains unknown. To address this question, we performed large-scale recordings from neurons in both somatosensory cortices (S1) while mice shared information between their hemispheres and discriminated between two categories of bilateral stimuli. When expert mice touched stimuli associated with reward, they moved their whiskers with greater bilateral symmetry. During this period, synchronous spiking and enhanced spike-field coupling emerged between the hemispheres. This coordinated activity was absent in stimulus-matched naive animals, indicating that interhemispheric (IH) binding was controlled by a goal-directed, internal process. In S1 neurons, the addition of ipsilateral touch primarily facilitated the contralateral, principal whisker response. This facilitation primarily emerged for reward-associated stimuli and was lost on trials where expert mice failed to respond. Taken together, these results reveal a novel state-dependent logic underlying bilateral integration in S1, where stimulus binding and facilitation are controlled by behavioral relevance.

neuroscience↗

bioRxiv2024

Epidural Spinal Cord Recordings (ESRs): Sources of Artifact in Stimulation Evoked Compound Action Potentials

IntroductionEvoked compound action potentials (ECAPs) measured using epidural spinal recordings (ESRs) during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain, as well as inform closed-loop control of SCS. Previous studies have used ECAPs to characterize the neural response to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact resulting from disturbance of the electrode/tissue interface during normal behavior. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model. MethodsWe characterized the sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode lead. Muscle paralytics were administered to block muscle activation preventing EMG from contaminating the recorded ECAPs. Concurrent EMG recordings of the longissimus, a long muscle of the back, were used to confirm a 2-4 millisecond (ms) latency source of EMG bleed-through that frequently contaminated the A-beta temporal window. Additionally, we obtained recordings approximately 5-10 minutes post-mortem after clear evoked A-beta and associated EMG responses ceased to characterize the representation of stimulation artifact across the array. ResultsSpinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby long muscles of the back, and motion artifact from multiple sources. In many cases, the capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. These sources of EMG can have phase shifts across the electrode array, very similar to the phase shift anticipated by propagation of an evoked A-beta fiber response across the array. This short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in cerebrospinal fluid between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of the recorded ECAP signal. ConclusionCareful controls must be implemented to accurately separate neural signal from the sources of artifact in spinal cord ECAPs. To address this, we suggest experimental procedures and associated reporting requirements necessary to disambiguate the underlying neural response from these confounds. These data are important to better understand the conceptual framework for recorded ESRs, with components such as ECAPs, EMG responses and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.

neuroscience↗

bioRxiv2024

A high-quality de novo genome assembly of Asian Crested Ibis (Nipponia Nippon) using long-read and Hi-C data

We present TtaoRef1, the highest-quality de novo genome assembly of Asian Crested Ibis (Nipponia Nippon) to date consisting of 134 scaffolds with a length of 1.25 Gb and N50 of 101,183,595 bp. This assembly was generated through the utilization of long-read sequencing and Hi-C data. The assessment of assembly quality, conducted via Benchmarking Universal Single-Copy Orthologs (BUSCO), revealed the presence of 96.8% of completely predicted single-copy genes. TtaoRef1 had 18 times longer N50 value than the previous assembly (ASM70822v1), Furthermore, we conducted the annotation of 24,681 protein-coding genes within the newly assembled genome sequences.

bioinformatics↗

bioRxiv2024

Comprehensive Whole Genome Sequencing Reveals Origins of Mutational Signatures Associated with Aging and Temozolomide Chemotherapy

In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of [~]40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair knockout in conjunction with additional repair deficiencies uncovers cryptic mutational patterns. We report how distinct mutational signatures are induced by TMZ upon sequential inactivation of DNA repair pathways, mirroring the acquisition of chemotherapy resistance by glioblastomas. The most toxic adduct induced by TMZ, O6-meG, is directly repaired by the O6-methylguanine-DNA methyltransferase (MGMT). In MGMT-/- cells, mismatch repair (MMR) leads to cell death and limits mutagenesis. MMR deficiency results in TMZ resistance, allowing the accumulation of [~]105 C>T substitutions corresponding to signature SBS11. Under these conditions, N-alkylated bases, processed by base excision repair (BER), limit cell survival. Without BER, 3-meA is read through via error-prone TLS, causing T>A substitutions but not affecting survival. Blocking BER after abasic site formation results in large deletions and TMZ hypersensitization. Our findings reveal potential vulnerabilities of TMZ-resistant tumors.

genomics↗

bioRxiv2024

Selective regulation of corticostriatal synapses by astrocytic phagocytosis

In the adult brain, neural circuit homeostasis depends on the constant turnover of synapses via astrocytic phagocytosis mechanisms. However, it remains unclear whether this process occurs in a circuit-specific manner. Here, we reveal that astrocytes target and reorganize excitatory synapses in the striatum. Using model mice lacking astrocytic phagocytosis receptors in the dorsal striatum, we found that astrocytes constantly remove corticostriatal synapses rather than thalamostriatal synapses. This preferential elimination suggests that astrocytes play a selective role in modulating corticostriatal plasticity and functions via phagocytosis mechanisms. Supporting this notion, corticostriatal long-term potentiation (LTP) and the early phase of motor sequence learning are dependent on astrocytic phagocytic receptors. Together, our findings demonstrate that astrocytes contribute to the connectivity and plasticity of the striatal circuit by preferentially engulfing a specific subset of excitatory synapses within brain regions innervated by multiple excitatory sources.

neuroscience↗

bioRxiv2024

An artificial intelligence accelerated virtual screening platform for drug discovery

Structure-based virtual screening is a key tool in early drug discovery, with growing interest in the screening of multi-billion chemical compound libraries. However, the success of virtual screening crucially depends on the accuracy of the binding pose and binding affinity predicted by computational docking. Here we developed a highly accurate structure-based virtual screen method, RosettaVS, for predicting docking poses and binding affinities. Our approach outperforms other state-of-the-art methods on a wide range of benchmarks, partially due to our ability to model receptor flexibility. We incorporate this into a new open-source artificial intelligence accelerated virtual screening platform for drug discovery. Using this platform, we screened multi-billion compound libraries against two unrelated targets, a novel ubiquitin ligase target KLHDC2 and the human voltage-gated sodium channel NaV1.7. On both targets, we discover hits, including seven novel hits (14% hit rate) to KLHDC2 and four novel hits (44% hit rate) to NaV1.7 with single digit micromolar binding affinities. Screening in both cases was completed in less than seven days. Finally, a high resolution X-ray crystallographic structure validates the predicted docking pose for the KLHDC2 ligand complex, demonstrating the effectiveness of our method in lead discovery.

biochemistry↗

bioRxiv2024

Sensory integration of food availability and population density during the diapause exit decision involves insulin-like signaling in Caenorhabditis elegans

Decisions made over long time scales, such as life cycle decisions, require coordinated interplay between sensory perception and sustained gene expression. The Caenorhabditis elegans dauer (or diapause) exit developmental decision requires sensory integration of population density and food availability to induce an all-or-nothing organismal-wide response, but the mechanism by which this occurs remains unknown. Here, we demonstrate how the ASJ chemosensory neurons, known to be critical for dauer exit, perform sensory integration at both the levels of gene expression and calcium activity. In response to favorable conditions, dauers rapidly produce and secrete the dauer exit-promoting insulin-like peptide INS-6. Expression of ins-6 in the ASJ neurons integrate population density and food level and can reflect decision commitment since dauers committed to exiting have higher ins-6 expression levels than those of non-committed dauers. Calcium imaging in dauers reveals that the ASJ neurons are activated by food, and this activity is suppressed by pheromone, indicating that sensory integration also occurs at the level of calcium transients. We find that ins-6 expression in the ASJ neurons depends on neuronal activity in the ASJs, cGMP signaling, a CaM-kinase pathway, and the pheromone components ascr#8 and ascr#2. We propose a model in which decision commitment to exit the dauer state involves an autoregulatory feedback loop in the ASJ neurons that promotes high INS-6 production and secretion. These results collectively demonstrate how insulin-like peptide signaling helps animals compute long-term decisions by bridging sensory perception to decision execution. Summary/Significance StatementAnimals must respond appropriately to multiple sensory stimuli to make informed decisions. It remains unclear how the nervous system is able to integrate different sensory cues and propagate that information towards making decisions over longer timescales. We use the nematode Caenorhabditis elegans to investigate how sensory integration occurs during the decision to exit diapause, a stress-resistant developmentally arrested state triggered by multiple sensory inputs including food availability and population density. We show how expression of an insulin-like peptide critical to dauer exit reflects the sensory integration process and decision commitment, and we dissect the regulation of this insulin-like peptides expression. Our study explicitly analyzes the relationship between neuronal activity and neuropeptide expression during a complex decision with diverse sensory inputs.

neuroscience↗

bioRxiv2024

Attentional inhibition by alpha power is modulated by faster theta rhythm and audio-visual congruency during natural speech perception

Audio-visual speech processing is a fundamental aspect of human communication; however, the neural oscillatory mechanisms, particularly those involving alpha rhythms, that underlie attention in tasks requiring attention and suppression remain unclear. To investigate this, we employed a complex audiovisual paradigm designed to explore how alpha rhythms, along with slower frequencies, monitor and integrate audio-visual information under congruent and incongruent conditions. Participants were presented with a TED Talk video while listening to auditory stimuli under four conditions: (1) congruent audio delivered to both ears, (2) congruent audio in one ear and incongruent audio in the other, with attention directed toward the congruent audio, (3) congruent audio in one ear and incongruent audio in the other, with attention directed toward the incongruent audio and (4) all-incongruent stimulus. To examine lateralized attention effects, participants were divided into left-attending and right-attending groups across individuals. By analysing fluctuations in alpha power with regards to audio-visual congruency and the side of attention, we observed a notable finding: alpha power fluctuations falling within the faster delta/theta range to the direction of attention, corresponding to task difficulty and accuracy. This result indicates a lateralized relationship between low-frequency rhythms and alpha-band activity, highlighting the role of alpha rhythms as a mediator of attention in audio-visual speech processing. Indeed, inhibitory alpha power fluctuation follows previous observations of sensory filtering. These findings underscore the importance of lateralized neural dynamics in tasks involving selective attention and suppression, providing new insights into the oscillatory mechanisms underlying audio-visual integration in human communication. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=56 SRC="FIGDIR/small/581860v3_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@1a7903org.highwire.dtl.DTLVardef@1fec365org.highwire.dtl.DTLVardef@ce4b12org.highwire.dtl.DTLVardef@1a2a4cd_HPS_FORMAT_FIGEXP M_FIG C_FIG This work describes how alpha power fluctuation varies as a function of attention during complex audiovisual stimuli. We identified that alpha power fluctuation in the delta-theta range increase as a function of task demands and corresponds to comprehension accuracy. By understanding how temporal-spatial alpha power dynamics influence attention, we describe a novel cross-frequency attention mechanism.

neuroscience↗

bioRxiv2024

Processing-bias correction with DEBIAS-M improves cross-study generalization of microbiome-based prediction models

Every step in common microbiome profiling protocols has variable efficiency for each microbe. For example, different DNA extraction kits may have different efficiency for Gram-positive and -negative bacteria. These variable efficiencies, combined with technical variation, create strong processing biases, which impede the identification of signals that are reproducible across studies and the development of generalizable and biologically interpretable prediction models. "Batch-correction" methods have been used to alleviate these issues computationally with some success. However, many make strong parametric assumptions which do not necessarily apply to microbiome data or processing biases, or require the use of an outcome variable, which risks overfitting. Lastly and importantly, existing transformations used to correct microbiome data are largely non-interpretable, and could, for example, introduce values to features that were initially mostly zeros. Altogether, processing bias currently compromises our ability to glean robust and generalizable biological insights from microbiome data. Here, we present DEBIAS-M (Domain adaptation with phenotype Estimation and Batch Integration Across Studies of the Microbiome), an interpretable framework for inference and correction of processing bias, which facilitates domain adaptation in microbiome studies. DEBIAS-M learns bias-correction factors for each microbe in each batch that simultaneously minimize batch effects and maximize cross-study associations with phenotypes. Using benchmarks of HIV and colorectal cancer classification from gut microbiome data, and cervical neoplasia prediction from cervical microbiome data, we demonstrate that DEBIAS-M outperforms batch-correction methods commonly used in the field. Notably, we show that the inferred bias-correction factors are stable, interpretable, and strongly associated with specific experimental protocols. Overall, we show that DEBIAS-M allows for better modeling of microbiome data and identification of interpretable signals that are reproducible across studies.

bioinformatics↗

bioRxiv2024

Stratification of viral shedding patterns in saliva of COVID-19 patients

Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we quantified individual-level viral dynamics and stratified them into three groups using a clustering approach. Notably, the three groups exhibited distinct differences viral RNA detection durations: 11.5 days (95% CI: 10.6 to 12.4), 17.4 days (16.6 to 18.2), and 30.0 days (28.1 to 31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral RNA detection without indicators that directly reflect an individuals immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.

microbiology↗

bioRxiv2024

Dissociating endogenous and exogenous delta activity during natural speech comprehension

Decoding human speech requires the brain to segment the incoming acoustic signal into meaningful linguistic units, ranging from syllables and words to phrases. Integrating these linguistic constituents into a coherent percept sets the root of compositional meaning and hence understanding. One important cue for segmentation in natural speech are prosodic cues, such as pauses, but their interplay with higher-level linguistic processing is still unknown. Here we dissociate the neural tracking of prosodic pauses from the segmentation of multi-word chunks using magnetoencephalography (MEG). We find that manipulating the regularity of pauses disrupts slow speech-brain tracking bilaterally in auditory areas (below 2 Hz) and in turn increases left-lateralized coherence of higher frequency auditory activity at speech onsets (around 25 - 45 Hz). Critically, we also find that multi-word chunks--defined as short, coherent bundles of inter-word dependencies--are processed through the rhythmic fluctuations of low frequency activity (below 2 Hz) bilaterally and independently of prosodic cues. Importantly, low-frequency alignment at chunk onsets increases the accuracy of an encoding model in bilateral auditory and frontal areas, while controlling for the effect of acoustics. Our findings provide novel insights into the neural basis of speech perception, demonstrating that both acoustic features (prosodic cues) and abstract processing at the multi-word timescale are underpinned independently by low-frequency electrophysiological brain activity.

neuroscience↗

bioRxiv2024

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

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

genomics↗