Biology subjects

Nguyen, D.

Publications and source records attributed to Nguyen, D..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

The ER protein translocation channel subunit Sbh1 controls virulence of Cryptococcus neoformans

The fungal pathogen Cryptococcus neoformans is distinguished by a cell wall-anchored polysaccharide capsule that is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with polypeptide translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins: Sec61, Sbh1, and Sss1. Sbh1, the most divergent, contains multiple phosphorylation sites, which may allow it to regulate entry into the secretory pathway in a species- and protein-specific manner. Absence of SBH1 causes a cell-wall defect in both Saccharomyces cerevisiae and C. neoformans, although other phenotypes differ. Notably, proteomic analysis showed that when cryptococci are grown in conditions that mimic aspects of the mammalian host environment (tissue culture medium, 37 {degrees}C, 5% CO2), a set of secretory and transmembrane proteins is upregulated in wild-type, but not in{Delta} sbh1 mutant cells. The Sbh1-dependent proteins show specific features of their ER targeting sequences that likely cause them to transit less efficiently into the secretory pathway. Many also act in cell-wall biogenesis, while several are known virulence factors; consistent with these observations, the C. neoformans {Delta}sbh1 mutant is avirulent in a mouse infection model. We conclude that, in the context of conditions encountered during infection, Sbh1 controls the entry of virulence factors into the secretory pathway of C. neoformans, and thereby regulates fungal pathogenicity. ImportanceCryptococcus neoformans is a yeast that causes almost 200,000 deaths worldwide each year, mainly of immunocompromised individuals. The surface structures of this pathogen, a protective cell wall surrounded by a polysaccharide capsule, are made and maintained by proteins that are synthesized inside the cell and travel outwards through the secretory pathway. A protein called Sbh1 is part of the machinery that determines which polypeptides enter this export pathway. We found that when Sbh1 is absent, both C. neoformans and the model yeast S. cerevisiae show cell wall defects. Lack of Sbh1 also changes the pattern of secretion of both transmembrane and soluble proteins, in a manner that depends on characteristics of their sequences. Notably, multiple proteins that are normally upregulated in conditions similar to those encountered during infection, including several needed for cryptococcal virulence, are no longer increased. Sbh1 thereby regulates the ability of this important pathogen to cause disease.

microbiology↗

bioRxiv2022

ER translocation of suboptimal targeting sequences depends on Sec61β/Sbh1 and its phosphorylation

The endoplasmic reticulum (ER) protein translocation channel subunit Sec61{beta}/Sbh1 is non-essential, but contains multiple phosphorylation sites suggesting a regulatory role in ER protein import. We show here that mutating two N-terminal, proline-flanked, phosphorylation sites in the Sbh1 cytosolic domain phenocopies the temperature-sensitivity of a yeast strain lacking SBH1/SBH2, and results in reduced translocation into the ER of an Sbh1-dependent substrate, Gls1. In a microscopic screen we show that about 12% of GFP-tagged secretory proteins depend on Sbh1 for translocation. Sbh1-dependent proteins have targeting sequences with less pronounced hydrophobicity and often no or an inverse charge bias. A subset of these proteins was dependent on N-terminal phosphorylation of Sbh1 and on the phospho-S/T-specific proline isomerase Ess1 (PIN1 in mammals) for ER import. We conclude that Sbh1 promotes ER translocation of substrates with suboptimal targeting sequences and that its activity is regulated by a conformational change induced by N-terminal phosphorylation.

biochemistry↗

bioRxiv2022

Proteomics identifies substrates and a novel component in hSnd2-dependent ER protein targeting

Protein import into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves targeting of precursor proteins to the ER and insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining depletion of the central hSnd2-component from HeLa cells with proteomic- and differential protein abundance-analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals.

cell biology↗

bioRxiv2022

WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

Metastatic breast cancer remains a major cause of cancer related deaths in women and there are few effective therapies against this advanced disease. Emerging evidence suggests that key steps of tumor progression and metastasis are controlled by reversible epigenetic mechanisms. Using an in vivo genetic screen, we identified WDR5 as an actionable epigenetic regulator that is required for metastatic progression in models of triple-negative breast cancer. We found that knockdown of WDR5 in breast cancer cells independently impaired their tumorigenic as well as metastatic capabilities. Mechanistically, WDR5 promotes cell growth by increasing ribosomal gene expression and translation efficiency in a KMT2-independent manner. Consistently, pharmacological inhibition or degradation of WDR5 impedes cellular translation rate and the clonogenic ability of breast cancer cells. Furthermore, combination of WDR5-targeting with mTOR inhibitors leads to potent suppression of translation and proliferation of breast cancer cells. These results reveal novel therapeutic strategies to treat metastatic breast cancer.

cancer biology↗

bioRxiv2022

Seasonal dynamics of the wild rodent faecal virome

Viral discovery studies in wild animals often rely on cross-sectional surveys at a single time point. As a result, our understanding of the temporal stability of wild animal viromes remains poorly resolved. While studies of single host-virus systems indicate that host and environmental factors influence seasonal virus transmission dynamics, comparable insights for whole viral communities in multiple hosts are lacking. Leveraging non-invasive faecal samples from a long-term wild rodent study, we characterised viral communities of three common European rodent species (Apodemus sylvaticus, A. flavicollis, and M. glareolus) living in temperate woodland over a single year. Our findings indicate that a substantial fraction of the rodent virome is seasonally transient and associated with vertebrate or bacteria hosts. Further analyses of one of the most abundant virus families, Picornaviruses, show pronounced temporal changes in viral richness and diversity, which were associated with concurrent and up to [~]3-month lags in host density, ambient temperature, rainfall and humidity, suggesting complex feedbacks from the host and environmental factors on virus transmission and shedding in seasonal habitats. Overall, this study emphasizes the importance of understanding the seasonal dynamics of wild animal viromes in order to better predict and mitigate zoonotic risks.

ecology↗

bioRxiv2022

Resveratrol increases tear production and spontaneous ocular pain after corneal abrasion in male, but not female, rats using a preclinical model of photorefractive keratectomy (PRK)

Photorefractive keratectomy (PRK) is an alternative to LASIK and can cause intense acute pain that is often not relieved by standard treatments. To assess potential therapeutics for this type of acute pain, appropriate preclinical models are needed. Herein we describe a rodent preclinical model of PRK and a multi-faceted approach to determine the therapeutic potential of resveratrol, a natural phytoestrogen, on pain, tear production, and the corneal epithelium. Studies were conducted in male and female Sprague-Dawley rats. Heptanol was applied to one eye and the superficial corneal epithelium was removed, mimicking the abrasion seen in PRK. Spontaneous pain was assessed with orbital tightening (OT) scores for 7 days. Corneal abrasion increased OT scores in both male and female rats with peak responses at 24 - 48 hours. Topical application of resveratrol had a sex-specific effect on OT scores and tear production. Resveratrol increased OT scores in abraded males, but not females, at 72 hours and 1 week after abrasion. Resveratrol dose-dependently increased tear production in abraded males, but had no effect in abraded females. While there was no correlation between OT score at 1 week and tear production, CGRP content of corneal nerves was positively correlated with 1 week OT score. There was also a significant increase in CD68-labeled macrophages in resveratrol-treated abraded corneas as compared to naive corneas. These findings demonstrate the usefulness of our preclinical PRK model for the assessment of ocular pain therapeutics and indicate that topical resveratrol may not be useful for managing PRK-induced pain.

neuroscience↗

bioRxiv2021

Kismet/CHD7/CHD8 affects gut biomechanics, the gut microbiome, and gut-brain axis in Drosophila melanogaster

The gut-brain axis may contribute to the pathophysiology of neurodevelopmental disorders, yet it is often unclear how risk genes associated with these disorders affect gut physiology in a manner that could impact microbial colonization. We addressed this question using Drosophila melanogaster with a null mutation in kismet, the ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, CHD7 and CHD8 are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found kismet mutant flies have a significant increase in gastrointestinal transit time, indicating functional homology of kismet with CHD7/CHD8 in vertebrates. To measure gut tissue mechanics, we used a high-precision force transducer and length controller, capable of measuring forces to micro-Newton precision, which revealed significant changes in the mechanics of kismet mutant guts, in terms of elasticity, strain stiffening, and tensile strength. Using 16S rRNA metagenomic sequencing, we also found kismet mutants have reduced diversity of gut microbiota at every taxonomic level and an increase in pathogenic taxa. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and measured courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of gut microbiome in the control strain reduced courtship activity. This result demonstrated that antibiotic treatment can have differential impacts on behavior that may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-brain axis to influence behavior. Based on our results, we also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neuronal development.

developmental biology↗

bioRxiv2021

HA and M2 sequences alter the replication of 2013-16 H1 Live Attenuated Influenza Vaccine Infection in Human Nasal Epithelial Cell cultures

From 2013-2016, the H1N1 component of live, attenuated influenza vaccine (LAIV) performed very poorly in contrast to the inactivated influenza vaccine. We utilized a primary, differentiated human nasal epithelial (hNEC) culture system to assess the replication differences between isogenic LAIVs containing the HA segment from either A/Bolivia/559/2013 (rBol), which showed poor vaccine efficacy, and A/Slovenia/2903/2015 (rSlov), which had restored reasonable vaccine efficacy. While there were minimal differences in infectious virus production in Madin-Darby Canine Kidney (MDCK) cells, the rSlov LAIV showed markedly improved replication in hNEC cultures at both 32{degrees}C and 37{degrees}C, demonstrating that the HA segment alone could impact LAIV replication. The rSlov-infected hNEC cultures showed stronger production of interferon and proinflammatory chemokines which might also be contributing to the increased overall vaccine effectiveness of the rSlov LAIV through enhanced recruitment and activation of immune cells. The introduction of an M2-S86A mutation had no positive effects on H1 LAIV replication in hNEC cultures, in contrast to the increased infectious virus production seen with that mutation in an H3 LAIV. No obvious defects in viral RNA packaging were detected, suggesting the HA function may be driving the differential infectious virus production in hNEC cultures. The use of physiologically relevant temperatures and primary cell cultures demonstrated that candidate LAIVs can replicate efficiently, which is a necessary property for effective vaccines.

microbiology↗

bioRxiv2021

Sonogenetic stimulation of the brain at a spatiotemporal resolution suitable for vision restoration

Remote, precisely controlled activation of the brain is a fundamental challenge in the development of brain-machine interfaces providing feasible rehabilitation strategies for neurological disorders. Low-frequency ultrasound stimulation can be used to modulate neuronal activity deep in the brain1-7, but this approach lacks spatial resolution and cellular selectivity and loads the brain with high levels of acoustic energy. The combination of the expression of ultrasound-sensitive proteins with ultrasound stimulation ( sonogenetic stimulation) can provide cellular selectivity and higher sensitivity, but such strategies have been subject to severe limitations in terms of spatiotemporal resolution in vivo8-10, precluding their use for real-life applications. We used the expression of large-conductance mechanosensitive ion channels (MscL) with high-frequency ultrasonic stimulation for a duration of milliseconds to activate neurons selectively at a relatively high spatiotemporal resolution in the rat retina ex vivo and the primary visual cortex of rodents in vivo. This spatiotemporal resolution was achieved at low energy levels associated with negligible tissue heating and far below those leading to complications in ultrasound neuromodulation6,11. We showed, in an associative learning test, that sonogenetic stimulation of the visual cortex generated light perception. Our findings demonstrate that sonogenetic stimulation is compatible with millisecond pattern presentation for visual restoration at the cortical level. They represent a step towards the precise transfer of information over large distances to the cortical and subcortical regions of the brain via an approach less invasive than that associated with current brain-machine interfaces and with a wide range of applications in neurological disorders.

neuroscience↗

bioRxiv2021

Across functional boundaries: making non-neutralizing antibodies to neutralize HIV-1 and mediate Fc-mediated effector killing of infected cells

In HIV-1 infection, many antibodies (Abs) are elicited to Envelope (Env) epitopes that are conformationally masked in the native trimer and are only available for antibody recognition after the trimer binds host cell CD4. Among these are epitopes within the Co-Receptor Binding Site (CoRBS) and the constant region 1 and 2 (C1-C2 or Cluster A region). In particular, C1-C2 epitopes map to the gp120 face interacting with gp41 in the native, closed Env trimer present on HIV-1 virions or expressed on HIV-1 infected cells. Antibodies targeting this region are therefore non-neutralizing and their potential as mediators of antibody depended cellular cytoxicity (ADCC) of HIV-1 infected cells diminished by a lack of available binding targets. Here we present the design of Ab-CD4 chimeric proteins that consist of the Ab-IgG1 of a CoRBS or Cluster A specificity to the extracellular domain 1 and 2 of human CD4. Our Ab-CD4 hybrids induce potent ADCC against infected primary CD4+ T cells and neutralize tier 1 and 2 HIV-1 viruses. Furthermore, competition binding experiments reveal that the observed biological activities rely on both the antibody and CD4 moieties confirming their cooperativity in triggering conformational rearrangements of Env. Our data indicate the utility of these Ab-CD4 hybrids as antibody therapeutics effective in eliminating HIV-1 through the combined mechanisms of neutralization and ADCC. This is also the first report of single-chain-Ab-based molecules capable of opening closed Env trimers on HIV-1 particles/infected cells to expose the Cluster A region and activate ADCC and neutralization against these non-neutralizing targets. ImportanceHighly conserved epitopes within the co-receptor binding site (CoRBS) and constant region 1 and 2 (C1C2 or Cluster A) are only available for antibody recognition after the HIV-1 Env trimer binds host cell CD4, therefore they are not accessible on virions and infected cells where the expression of CD4 is downregulated. Here we have developed new antibody fusion molecules in which domains 1 and 2 of soluble human CD4 are linked with monoclonal antibodies of either the CoRBS or Cluster A specificity. We optimized the conjugation sites and linker lengths to allow each of these novel bispecific fusion molecules to recognize native "closed" Env trimers and induce the structural rearrangements required for exposure of the epitopes for antibody binding. Our in vitro functional testing shows that our Ab-CD4 molecules can efficiently target and eliminate HIV-1 infected cells through antibody depended cellular cytoxicity (ADCC) and inactivate HIV-1 virus through neutralization.

immunology↗

bioRxiv2021

Neuronal responses to focused ultrasound are gated by pre-stimulation brain rhythms

BackgroundOwing to its high spatial resolution and penetration depth, transcranial focused ultrasound stimulation (tFUS) is one of the most promising approaches to non-invasive neuromodulation. Identifying the impact of the stimulation waveform and endogenous neural activity on neuromodulation outcome is critical to harnessing the potential of tFUS. ObjectiveHere we tested a new form of tFUS where the amplitude of the ultrasonic waveform is modulated at a rate much slower than the operating frequency. Moreover, we sought to identify the relationship between pre-stimulation neural activity and the neuronal response to tFUS. MethodsWe applied three minutes of amplitude modulated (AM) tFUS at 40 Hz to the rat hippocampus while recording local field potentials (LFP) and multi-unit activity (MUA)from the sonicated region. To assess the role of AM, we also tested continuous-wave (CW) stimulation. ResultsAM tFUS reduced firing rate during and immediately after stimulation. On the other hand, CW tFUS produced an acute firing rate increase that was abolished after sonication. For both waveforms, firing rate changes were stronger in units exhibiting high baseline LFP power, particularly in the gamma band (30-250 Hz). The neuromodulatory effect was also influenced by the prevalence of sharp wave ripples (SWR) during the pre-stimulation period, with firing rates modulated by up to 33% at units showing frequent baseline SWR. ConclusionOur findings suggest that AM and CW tFUS produce qualitatively different neuronal outcomes, and that baseline rhythms may effectively "gate" the response to tFUS.

neuroscience↗

bioRxiv2021

A Neural Model of RNA Splicing: Learning Motif Distances with Self-Attention and Toeplitz Max Pooling

Alternative RNA splicing is an important regulator of tissue development and specificity, and a relevant mechanism in cancer progression. There exists a strong motivation to disentangle the rules that govern RNA splicing, in part because this knowledge may one day yield new clinically relevant diagnostic tools and therapeutics. It is no easy to task to reverse engineer how the splicesome machinery choreographs the removal and addition of RNA elements following transcription. Here, we propose an interpretable neural network called the Toeplitz ATtention Architecture (TATA), which learns distance-dependent motif interactions through a novel Toeplitz max pool layer that captures the relative distance between interacting CNN filters. TATA is a completely transparent "clear-box" solution: every model parameter is human-interpretable. We validate TATA on simulated data, then apply it to real data to identify putative cis-regulatory elements that interact with primary RNA splice sites.

bioinformatics↗

bioRxiv2021

Maturation of Human Long-lived Plasma Cells Results in Resistance to Apoptosis by Transcriptional and Epigenetic Regulation

Antibody secreting cells (ASC) circulate after vaccination and migrate to the bone marrow (BM) where a subset known as long-lived plasma cells (LLPC) persist and secrete antibodies for a lifetime. The mechanisms of how circulating ASC become LLPC are not well elucidated. Here, we show that human blood ASCs have distinct morphology, transcriptomes, and epigenetics compared to BM LLPC. LLPC acquire transcriptional and epigenetic changes in the apoptosis pathway to support their survival. Upregulation of pro-survival gene expression accompanies downregulation of pro-apoptotic gene expression in LLPC. While pro-apoptotic gene loci are less accessible, pro-survival gene loci are not always accompanied by accessibility changes. Importantly, we show similar LLPC morphological and transcriptional maturation of blood ASC in response to the novel in vitro BM mimetic. In all, our study demonstrates that blood ASC in the BM microniche must undergo morphological and molecular changes to mature into apoptotic-resistant LLPC.

immunology↗

bioRxiv2021

Inter-Subject Correlation during New Music Listening: A Study of Electrophysiological and Behavioral Responses to Steve Reich's Piano Phase

Musical minimalism utilizes the temporal manipulation of restricted collections of rhythmic, melodic, and/or harmonic materials. One example, Steve Reichs Piano Phase, offers listeners readily audible formal structures containing unpredictable events at local levels. Pattern recurrences may generate strong expectations which are violated by small temporal and pitch deviations. A hyper-detailed listening strategy prompted by these minute deviations stands in contrast to the type of listening engagement typically cultivated around functional tonal Western music. Recent research has suggested that the inter-subject correlation (ISC) of electroencephalographic (EEG) responses to natural audio-visual stimuli objectively indexes a state of "engagement", demonstrating the potential of this approach for analyzing music listening. But can ISCs capture engagement with minimal music, which features less obvious expectation formation and has historically received a wide range of reactions? To approach this question, we collected EEG and continuous behavioral (CB) data while 30 adults listened to an excerpt from Steve Reichs Piano Phase, as well as three controlled manipulations and a popular-music remix of the work. Our analyses reveal that EEG and CB ISC are highest for the remix stimulus and lowest for our most repetitive manipulation. In addition, we found no statistical differences in overall EEG ISC between our most musically meaningful manipulations and Reichs original piece. We also found that aesthetic evaluations corresponded well with overall EEG ISC. Finally we highlight co-occurrences between stimulus events and time-resolved EEG and CB ISC. We offer the CB paradigm as a useful analysis measure and note the value of minimalist compositions as a limit case for studying music listening using EEG ISC. We show that ISC is less effective at measuring engagement with this minimalist stimulus than with popular music genres and argue that this may be due to a difference between the type of engagement measured by ISC and the particular engagement patterns associated with minimalism.

neuroscience↗

bioRxiv2021

Xenogeneic Skin Transplantation Promotes Angiogenesis and Tissue Regeneration Through Vitamin D-Activated Trem2+ Macrophages

Skin allo- and xenotransplantation are the standard treatment for major burns when donor sites for autografts are not available and have been shown to significantly accelerate wound healing. Although the cellular elements of foreign grafts are rejected, the extracellular matrix components integrate into the wound and may underlie their beneficial effects on wound healing. The molecular mechanisms defining the relationship between the immune response to foreign grafts and their impact on wound healing have not been fully elucidated. Here, we investigated changes in collagen architecture after xenogeneic implantation of clinically available human biologic scaffolds. We show that collagen deposition in response to the implantation of human split-thickness skin grafts (hSTSG) containing live cells recapitulates normal skin architecture, whereas human acellular dermal matrix (ADM) grafts led to highly aligned collagen deposition, characteristic of fibrosis and scar. Using single-cell RNA-sequencing, we show that macrophage differentiation in response to hSTSG is driven by vitamin D (VD) signaling toward Trem2+ subpopulations with an enrichment of pro-angiogenic and anti-fibrotic transcriptomic programs. We subsequently induced this regenerative subpopulation in vitro by treating bone marrow-derived cells with vitamin D3 and found that hydrogel delivery of Trem2+ macrophages significantly accelerated wound closure in a human-like murine excisional wound model. Our study identifies the preclinical therapeutic potential of Trem2+ macrophages to mitigate fibrosis and promote wound healing and provides a novel effective strategy to develop advanced cell therapies for complex wounds. One Sentence SummaryVitamin D-activated Trem2+ macrophages promote angiogenesis and mitigate fibrosis, providing a novel effective strategy to develop advanced cell therapies for complex wounds.

immunology↗

bioRxiv2021

A covalently crosslinked bioink for multi-materials drop-on-demand 3D bioprinting of three-dimensional cell cultures

In vitro three-dimensional (3D) cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here we report a versatile bioink comprised of a 4-arm PEG based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a drop-on-demand 3D bioprinting platform consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D structures comprising multiple hydrogel environments in the one structure in a standard 96-well plate format. The platform compatibility for biological applications was validated using pancreatic ductal adenocarcinoma cancer (PDAC) cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.

bioengineering↗

bioRxiv2021

The Need for Sustainable Leadership in Academia - a German Case Study

Academic leaders are selected based on their publication record, citation index and acquisition of third party funding. However, heading a successful research team, also requires leadership skills. Despite the clear need, leadership development has been systematically neglected in the present academic system. At the same time, growing evidence suggests that leadership styles of academic supervisors can dramatically affect the mental health of academic employees as well as drive highly skilled researchers out of academia. Here, we assessed the current state of academic leadership in the German academic system by surveying 368 participants currently employed in academia in Germany. We report that 64% of current academic leaders did not feel prepared for their current position while 86% of participants expressed their interest in leadership development programs offered by their research institutions. Our results highlight the demand for leadership development programs in German academic institutions to ensure a more efficient academic system.

scientific communication and education↗

bioRxiv2020

Transposon- and genome dynamics in the fungal genus Neurospora: insights from nearly gapless genome assemblies

BackgroundA large portion of nuclear DNA is composed of transposable element (TE) sequences, whose transposition is controlled by diverse host defense strategies in order to maintain genomic integrity. One such strategy is the fungal-specific Repeat-Induced Point (RIP) mutation that hyper-mutates repetitive DNA sequences. While RIP is found across Fungi, it has been shown to vary in efficiency. To date, detailed information on the TE landscapes and associated RIP patterns exist only in a few species belonging to highly divergent lineages. ResultWe investigated 18 nearly gapless genome assemblies of ten Neurospora species, which diverged from a common ancestor about 7 MYA, to determine genome-wide TE distribution and their associated RIP patterns. We showed that the TE contents between 8.7-18.9% covary with genome sizes that range between 37.8-43.9 Mb. Degraded copies of Long Terminal Repeat (LTR) retrotransposons were abundant among the identified TEs, and these are distributed across the genome at varying frequencies. In all investigated genomes, TE sequences had signs of numerous C-to-T substitutions, suggesting that RIP occurred in all species. RIP signatures in all genomes correlated with TE-dense regions. ConclusionsEssentially gapless genome assemblies allowed us to identify TEs in Neurospora genomes, and reveal that TEs contribute to genome size variation in this group. Our study suggests that TEs and RIP are highly correlated in Neurospora, and hence, the pattern of interaction is conserved over the investigated evolutionary timescale. We show that RIP signatures can be used to facilitate the identification of TE-rich region in the genome.

genomics↗