Biology subjects

Lee, C.-C.

Publications and source records attributed to Lee, C.-C..

At least 19 recordsLinked to original sources

bioRxiv2026

Relating layer fMRI signals to acoustics and intracranial neuronal activity in the human auditory cortex in a naturalistic design

Naturalistic auditory perception engages feedforward and feedback dynamics across cortical depths, yet how these are organized in the human auditory cortex has been difficult to verify noninvasively. Here, we examine depth-dependent coupling between neuronal activity and fMRI during passive music listening. Depth-specific fMRI responses were modeled using neuronal oscillation envelopes elicited by the same naturalistic stimuli from a separate group of patients under intracranial EEG monitoring. From deep toward superficial depths, the relationship between oscillatory power and fMRI responses systematically changed: alpha/beta activity (8-30 Hz) was increasingly associated with negative fMRI responses, mapping top-down feedback, while gamma band (>30 Hz) oscillations showed increasingly positive associations. Relative to a purely acoustical fMRI baseline, broadband high-frequency activity (>70 Hz), a proxy for neuronal firing, showed the strongest coupling to BOLD signals at intermediate cortical depths receiving feedforward inputs from earlier auditory pathways. Our findings reveal a spectrolaminar organization of neurovascular coupling in the human auditory cortex.

neuroscience↗

bioRxiv2026

Enhancing Adult Neurogenesis Rescues Hippocampal Cognitive Functions in an Alzheimer's Mouse Model

Alzheimers disease (AD) is the most prevalent form of dementia, characterized by progressive memory loss, cognitive decline, and emotional dysregulation. Adult hippocampal neurogenesis (AHN) critically contributes to cognition and mood but undergoes precipitous decline during AD progression. Here, we investigated whether enhancing AHN through genetic expansion of endogenous neural stem cells (NSC) ameliorates AD-related phenotypes. Using lentiviral overexpression of the cell cycle regulators Cdk4 and CyclinD1 in the dentate gyrus of 3xTg-AD mouse, we show that enhancing AHN partially rescues hippocampal-specific cognitive functions, namely: spatial navigation and exploratory behavior. These findings show that endogenous NSC can be exploited to ameliorate hippocampal cognitive functions in AD, providing additional evidence for exploiting AHN as a promising therapeutic target for neurodegenerative disease.

neuroscience↗

bioRxiv2026

STING-STAT3-SOX18 Axis Drives EndMT and Epigenetic Reprogramming in SAVI Lung Fibrosis

A high prevalence of early-onset interstitial lung disease, including pulmonary fibrosis, in pediatric patients with Stimulator of interferon genes (STING)-Associated Vasculopathy with onset in infancy (SAVI) suggests a critical role for the cGAS-STING pathway in the pathogenesis of pulmonary fibrosis. We identified an endothelial-to-mesenchymal transition (EndMT) signature in lesional lung biopsies from SAVI patients, marked by a loss of endothelial and acquisition of mesenchymal markers. Consistently, induced pluripotent stem cell-derived endothelial cells (iECs) from SAVI patients harboring gain-of-function STING1 mutations spontaneously undergo EndMT, a process rescued in isogenic-correction. In endothelial cells, STING activation induces IRF3-independent STAT3 phosphorylation, initiating a SLUG-dependent mesenchymal transcriptional program while repressing SOX18 and an epigenetically-regulated endothelial maintenance network. Our studies define a non-canonical cGAS-STING-STAT3 signaling axis that couples a mesenchymal transcriptional program with epigenetic silencing of an endothelial maintenance program, promoting TGF{beta}-independent STING-mediated EndMT and endothelial dysfunction, and suggesting STING as a therapeutic target for inflammatory pulmonary fibrosis.

cell biology↗

bioRxiv2025

Viral transcriptional regulators extensively rewire host pathways through diverse mechanisms

Viral transcriptional regulators (vTRs) reprogram host gene regulatory networks to promote replication, persistence, and immune evasion. Despite the identification of hundreds of vTRs in human viruses, how they rewire host pathways remains unclear. Here, we systematically profiled 95 vTRs from diverse human viruses across multiple functional assays. vTRs perturb immune, cell proliferation/death, and signaling pathways through various mechanisms; some bind DNA directly, others cooperate or antagonize human transcription factors (hTFs), and some remodel chromatin. vTRs can act as activators or repressors and recruit similar but not identical repertoires of proteins as hTFs. These findings reveal vTRs as versatile transcriptional modulators that converge on conserved host "pressure points" while diversifying across pathways to promote viral replication and persistence. Notably, many vTR dysregulate genes within autoimmune, neurological, and cardiovascular risk loci, revealing mechanistic links to disease. Together, we provide a comprehensive resource for understanding and targeting viral control of human transcription.

genomics↗

bioRxiv2025

Dynamic and Heterogeneous Distribution of Trichomonasvirus Species in Trichomonas vaginalis

Trichomonasvirus (TVV) is a double-stranded RNA virus from the Pseudototiviridae family that exclusively infects Trichomonas vaginalis, the protozoan responsible for the most common non-viral sexually transmitted infection. Within the Trichomonasvirus genus, five distinct viral species have been identified, and intriguingly, a single T. vaginalis isolate can simultaneously harbor multiple TVV species. Previous studies have explored the impact of TVV infection on the physiology and virulence of T. vaginalis, yet findings remain inconsistent and often contradictory. We propose that these discrepancies stem from the heterogeneous intracellular distribution of TVV within individual cells of the same T. vaginalis isolate. To investigate this, we employed ultra-deep single-cell RNA sequencing and immunofluorescence assays to examine multiple T. vaginalis isolates. Our results revealed striking variability in the proportion of infected cells carrying the same viral species, even within a single isolate. The present study is the first to demonstrate the dynamic and non-uniform intracellular distribution of TVV at the single-cell level. These findings challenge previous assumptions and provide a new perspective on the intricate virus-host interactions between TVV and T. vaginalis, offering new avenues for further research into their complex relationship. Author SummaryTrichomonas vaginalis is a parasitic protozoan responsible for the most prevalent non-viral sexually transmitted infection worldwide. In 1985, researchers discovered a double-stranded RNA (dsRNA) virus within T. vaginalis, which was later named Trichomonasvirus (TVV). This virus is believed to influence the hosts gene expression, impacting cytoadherence, drug susceptibility, and virulence proteins. However, studies on TVV-host interaction have produced conflicting results, with some genes appearing upregulated in one experiment but downregulated in another or vice versa. We hypothesize that these inconsistencies stem from the non-uniform distribution of TVV among individual cells within the same T. vaginalis isolate. Based on the experimental data from ultra-deep single-cell sequencing and immuno-localization, our study reveals that TVVs intracellular distribution is highly heterogeneous and dynamic. These findings challenge the prevailing assumption that TVV is uniformly and statically distributed. This heterogeneity underscores the need to reassess previous research on TVV-T. vaginalis interactions, as earlier studies may have overlooked this crucial factor.

microbiology↗

bioRxiv2024

Comparative genomics of the sexually transmitted parasite Trichomonas vaginalis reveals relaxed and convergent evolution and genes involved in spillover from birds to humans

Trichomonas vaginalis is the causative agent of the venereal disease trichomoniasis which infects men and women globally and is associated with serious outcomes during pregnancy and cancers of the human reproductive tract. Trichomonads parasitize a range of hosts in addition to humans including birds, livestock, and domesticated animals. Recent genetic analysis of trichomonads recovered from columbid birds has provided evidence that these parasite species undergo frequent host-switching, and that a current epoch spillover event from columbids likely gave rise to T. vaginalis in humans. We undertook a comparative evolutionary genomics study of seven trichomonad species, generating chromosome-scale reference genomes for T. vaginalis and its avian sister species Trichomonas stableri, and assemblies of five other species that infect birds and mammals. Human-infecting trichomonad lineages have undergone recent and convergent genome size expansions compared to their avian sister species, and the major contributor to their increased genome size is increased repeat expansions, especially multicopy gene families and transposable elements, with genetic drift likely a driver due to relaxed selection. Trichomonads have independently host-switched twice from birds to humans, and genes implicated in the transition to the human host include those associated with host tissue adherence and phagocytosis, extracellular vesicles, and CAZyme virulence factors.

microbiology↗

bioRxiv2024

Repeated evolution of supergenes on an ancient social chromosome

Supergenes are non-recombining chromosomal regions that code for complex polymorphic traits. Advances in population genomics have uncovered supergenes associated with diverse traits, ranging from butterfly wing patterns to floral morphs. In ants, two supergenes on non-homologous "social chromosomes" in Solenopsis and Formica are associated with social polymorphism, with either single queen (monogyne) or multiple queens (polygyne) colonies. We discovered a new supergene associated with similar polymorphism in the desert ant Cataglyphis niger. Despite Cataglyphis being more closely related to Formica than Solenopsis, its social chromosome is homologous to that of Solenopsis, with conservation of synteny in gene content and order. This suggests that the social chromosome is ancient, dating back to the common ancestor of Solenopsis and Cataglyphis, at least 90 million years ago. Low sequence divergence between supergene haplotypes in both Solenopsis and Cataglyphis suggests that the two supergenes evolved recently and independently in the two divergent lineages on this ancient social chromosome. Comparative analysis of hymenopteran genomes further revealed a bee chromosome homologous to the ants social chromosome. The ant social chromosome contains the largest set of genes that are conserved as a linkage group across ant and bee genomes. This conserved gene set is enriched for olfactory functions, most notably a large number of odorant-binding proteins. The conservation of this gene set suggests that this chromosome plays an important role in social behavior across social Hymenoptera. We propose that the conserved gene set in the social chromosome was repeatedly used as a pre-adapted toolkit for the evolution of social traits in general, and specifically in the evolution of polygyne social structure in ants.

evolutionary biology↗

bioRxiv2024

Naa10 regulates hippocampal neurite outgrowth via Btbd3 N-α-acetylation-mediated actin dynamics

Protein N--acetylation is widespread in eukaryotes, yet its neuronal role remains unclear. Mutations in human N--acetyltransferase 10 (NAA10) lead to developmental defects affecting brain function, such as intellectual disability and autism. We found that hippocampal CA1-specific Naa10-knockout mice exhibit anxiety and reduced hippocampal dendritic complexity. Mechanistically, Naa10 promotes neurite outgrowth by acetylating BTB/POZ domain-containing protein 3 (Btbd3), crucial for the interaction of Btbd3 with filamentous actin (F-actin)-capping protein subunit beta (CapZb). Disrupting the Btbd3/CapZb interaction, either through Naa10 knockout or by expressing an N--acetylation-defective Btbd3 mutant, diminishes CapZb binding to F-actin and reduces neurite outgrowth. Moreover, cytochalasin D, a compound like CapZb in capping the barbed end of F-actin, rescues the Naa10 knockout-induced neurite reduction in hippocampal primary neurons. These findings unveil the role of Naa10 in enhancing hippocampal neurite outgrowth through the Btbd3-CapZb-F-actin axis, shedding light on potential mechanisms underlying X-linked Ogden syndrome resulting from human NAA10 mutations. eTOCChou et al. demonstrate that Naa10 promotes neurite outgrowth by N-acetylating Btbd3, facilitating the binding of the filamentous actin capping protein subunit beta (CapZb) to F-actin. Their study establishes a connection between protein N--acetylation and neuronal function, providing insight into the mechanism underlying brain disorders associated with human NAA10 mutations. HIGHLIGHTSO_LIHippocampal CA1-specific Naa10 KO leads to anxiety C_LIO_LIHippocampal CA1-specific Naa10 KO reduces hippocampal dendritic complexity C_LIO_LINaa10 promotes neurite outgrowth by N-acetylating Btbd3 C_LIO_LINaa10-mediated Btbd3 N--acetylation promotes CapZb binding to F-actin C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/583166v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@180da41org.highwire.dtl.DTLVardef@7921c6org.highwire.dtl.DTLVardef@9859b0org.highwire.dtl.DTLVardef@28687c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

Tyrosine protein-kinase 2 (TYK2), a member of the Janus kinase family, mediates inflammatory signaling through multiple cytokines, including interferon- (IFN), interleukin (IL)-12, and IL-23. Missense mutations in TYK2 are associated with protection against type 1 diabetes (T1D), and inhibition of TYK2 shows promise in the management of other autoimmune conditions. Here, we evaluated the effects of specific TYK2 inhibitors (TYK2is) in pre-clinical models of T1D. First, human {beta} cells, cadaveric donor islets, and iPSC-derived islets were treated in vitro with IFN in combination with a small molecule TYK2i (BMS-986165 or a related molecule BMS-986202). TYK2 inhibition prevented IFN-induced {beta} cell HLA class I up-regulation, endoplasmic reticulum stress, and chemokine production. In co-culture studies, pre-treatment of {beta} cells with a TYK2i prevented IFN-induced activation of T cells targeting an epitope of insulin. In vivo administration of BMS-986202 in two mouse models of T1D (RIP-LCMV-GP mice and NOD mice) reduced systemic and tissue-localized inflammation, prevented {beta} cell death, and delayed T1D onset. Transcriptional phenotyping of pancreatic islets, pancreatic lymph nodes (PLN), and spleen during early disease pathogenesis highlighted a role for TYK2 inhibition in modulating signaling pathways associated with inflammation, translational control, stress signaling, secretory function, immunity, and diabetes. Additionally, TYK2i treatment changed the composition of innate and adaptive immune cell populations in the blood and disease target tissues, resulting in an immune phenotype with a diminished capacity for {beta} cell destruction. Overall, these findings indicate that TYK2i has beneficial effects in both the immune and endocrine compartments in models of T1D, thus supporting a path forward for testing TYK2 inhibitors in human T1D.

physiology↗

bioRxiv2024

miR-146a-5p mediates inflammation-induced β cell mitochondrial dysfunction and apoptosis

We previously showed that miR-146a-5p is upregulated in pancreatic islets treated with pro-inflammatory cytokines. Others have reported that miR-146a-5p overexpression is associated with {beta} cell apoptosis and impaired insulin secretion. However, the molecular mechanisms mediating these effects remain elusive. To investigate the role of miR-146a-5p in {beta} cell function, we developed stable MIN6 cell lines to either overexpress or inhibit the expression of miR-146a-5p. Monoclonal cell populations were treated with pro-inflammatory cytokines (IL-1{beta}, IFN{gamma}, and TNF) to model type 1 diabetes (T1D) in vitro. We found that overexpression of miR-146a-5p increased cell death under conditions of inflammatory stress and led to mitochondrial membrane depolarization, whereas inhibition of miR-146a-5p reversed these effects. Additionally, inhibition of miR-146a-5p increased insulin secretion, mitochondrial DNA copy number, respiration rate, and ATP production Further, RNA sequencing data showed enrichment of pathways related to insulin secretion, apoptosis, and mitochondrial function when the expression levels of miR-146a-5p were altered. Finally, a temporal increase in miR-146a-5p expression levels and a decrease in mitochondria function markers was observed in islets derived from NOD mice. Collectively, these data suggest that miR-146a-5p may promote {beta} cell dysfunction and death during inflammatory stress by suppressing mitochondrial function.

molecular biology↗

bioRxiv2023

Histone Deacetylase Inhibitors Prevent Cytokine-Induced β Cell Dysfunction Through Restoration of Stromal Interaction Molecule 1 Expression and Activation of Store-Operated Calcium Entry

Histone deacetylase inhibitors (HDIs) modulate {beta} cell function in preclinical models of diabetes; however, the mechanisms underlying these beneficial effects have not been determined. In this study, we investigated the impact of the HDI sodium butyrate (NaB) on {beta} cell function and calcium (Ca2+) signaling using ex vivo and in vitro models of diabetes. Our results show that NaB significantly improved glucose-stimulated insulin secretion in islets from human organ donors with type 2 diabetes and in cytokine-treated INS-1 {beta} cells. Consistently, NaB partially rescued glucose-stimulated Ca2+ oscillations in mouse islets treated with proinflammatory cytokines. Because the oscillatory phenotype of Ca2+ in the {beta} cell is governed by changes in endoplasmic reticulum (ER) Ca2+ levels, next we explored the relationship between NaB and store-operated calcium entry (SOCE), a rescue mechanism that acts to refill ER Ca2+ levels through STIM1-mediated gating of plasmalemmal Orai channels. We found that NaB treatment preserved basal ER Ca2+ levels and restored SOCE in IL-1{beta}-treated INS-1 cells. Furthermore, we linked these changes with the restoration of STIM1 levels in cytokine-treated INS-1 cells and mouse islets, and we found that NaB treatment was sufficient to prevent {beta} cell death in response to IL-1{beta} treatment. Mechanistically, NaB counteracted cytokine-mediated reductions in phosphorylation levels of key signaling molecules, including AKT, ERK1/2, glycogen synthase kinase-3 (GSK-3), and GSK-3{beta}. Taken together, these data support a model whereby HDI treatment promotes {beta} cell function and Ca2+ homeostasis under proinflammatory conditions through STIM1-mediated control of SOCE and AKT-mediated inhibition of GSK-3.

physiology↗

bioRxiv2022

Electrophysiological population dynamics reveal context dependencies during decision making in human frontal cortex

During economic choice, evidence from monkeys and humans suggest that activity in the orbitofrontal cortex (OFC) encodes the subjective values of options under consideration. Monkey data further suggests that value representations in the OFC are context dependent, representing subjective value in a way influenced by the decision makers recent experience. Using stereo electroencephalography (sEEG) in human subjects, we investigated the neural representations of both past and present subjective values in the OFC, insula, cingulate and parietal cortices, amygdala, hippocampus and striatum. Patients with epilepsy (n=20) reported their willingness to pay--a measure of subjective value--for snack food items in a Becker-DeGroot-Marschack (BDM) auction task. We found that the high frequency power (gamma and high-gamma bands) in the OFC positively correlated with the current subjective value but negatively correlated with the subjective value of the good offered on the last trial - a kind of temporal context dependency not yet observed in humans. These representations were observed at both the group level (across electrode contacts and subjects) and at the level of individual contacts. Noticeably, the majority of significant contacts represented either the present or past subjective value, but not both. A dynamic dimensionality-reduction analysis of OFC population trajectories suggested that the past trial begin to influence activity early in the current trial after the current offer was revealed, and that these two properties--current and past subjective values--dominate the electrophysiological signals. Together, these findings indicate that information about the value of the past and present rewards are simultaneously represented in the human OFC, and offer insights into the algorithmic structure of context-dependent computation during human economic choice.

neuroscience↗

bioRxiv2022

Stromal Interaction Molecule 1 Maintains β Cell Identity and Function in Female Mice through Preservation of G Protein-Coupled Estrogen Receptor 1 Signaling

Loss of pancreatic {beta} cell mass, identity, and function contribute to the development of diabetes. Here, we show that the endoplasmic reticulum (ER) calcium sensor, stromal interaction molecule 1 (STIM1), is critical for the maintenance of {beta} cell function in female mice. When mice with {beta} cell-specific deletion of STIM1 (STIM1{Delta}{beta}) were challenged with high-fat diet, {beta} cell dysfunction was observed in female, but not male, mice. Impaired glucose tolerance was accompanied by reductions in {beta} cell mass, a concomitant increase in cell mass, and significant reductions in the expression of markers of {beta} cell maturity, including MafA and UCN3. Mechanistic assays demonstrated that the sexually dimorphic phenotype observed in STIM1{Delta}{beta} mice was due in part to loss of signaling through the noncanonical 17-{beta} estradiol receptor, GPER1. Together, these data suggest that STIM1 orchestrates pancreatic {beta} cell function and identity through GPER1-mediated estradiol signaling.

cell biology↗

bioRxiv2022

Visual stimuli modulate local field potentials but drive no high-frequency activity in human auditory cortex

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices. Whether these influences reflect active visual processing in human auditory cortices (ACs), which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants (7 women, 9 men) with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Analyses of intracranial event-related potentials (iERP) suggested cross-sensory responses to visual stimuli in ACs, which lagged the earliest auditory responses by several tens of milliseconds. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15-30-Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs. Significance StatementVisual information has a profound influence on auditory processing, particularly in noisy conditions. These "cross-sensory" influences start already in auditory cortices, the brain area that processes sound signals. It has, however, been unclear whether auditory cortex actively processes visual information or whether visual signals only change the way sounds are processed. We studied this question by neurophysiological recordings from 16 participants with epilepsy who had electrodes implanted in their brains due to medical reasons. Using these intracranial recordings, we show that cross-sensory visual information modulates sound processing but triggers no high-frequency activity -- a correlate of local neuronal firing -- in auditory cortex. This result provides important information on the role of sensory areas in multisensory processing in the human brain.

neuroscience↗

bioRxiv2022

SERCA2 regulates proinsulin processing and processing enzyme maturation in the pancreatic β cell

Increased circulating levels of incompletely processed insulin (i.e. proinsulin) are observed clinically in both type 1 and type 2 diabetes; however, the mechanisms underlying impaired proinsulin processing remain incompletely understood. Here, we identify the sarcoendoplasmic reticulum Ca2+ ATPase-2 (SERCA2) pump and {beta} cell ER Ca2+ as key regulators of systemic glucose tolerance and proinsulin processing. We generated mice with a {beta} cell-specific SERCA2 deletion ({beta}S2KO) and SERCA2 deficient INS-1 cells to show that SERCA2 loss increases systemic and pancreatic levels of proinsulin protein and leads to aberrant localization of proinsulin within the proximal {beta} cell secretory pathway. These defects in proinsulin processing were linked to reduced maturation of the proinsulin processing enzymes PC1/3 and PC2, suggesting a model whereby chronic ER Ca2+ depletion in the {beta} cell, which is observed in many pathological conditions, impairs the spatial regulation of prohormone trafficking, processing, and maturation within the {beta} cell secretory pathway.

physiology↗

bioRxiv2022

Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants

The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals receiving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a "Hybrid" vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specific RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.

microbiology↗

bioRxiv2021

The complete mitochondrial genome of a parthenogenetic ant, Monomorium triviale (Hymenoptera: Formicidae)

Monomorium is one of the most species-rich yet taxonomically problematic ant genus. An East Asian species, M. triviale Wheeler, W.M., 1906, are reproduced by obligate thelytokous parthenogenesis and performs strict reproductive division of labor. We sequenced the M. triviale mitogenome using next-generation sequencing methods. The circular mitogenome of M. triviale was 16,290 bp in length, consisting of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNAs, and a single non-coding region of 568 bp. The base composition was AT-biased (82%). Gene order rearrangements were detected and likely to be unique to the genus Monomorium. We announce the M. triviale mitogenome as additional genomic resources for elucidating phylogenetic and taxonomic problems of Monomorium and comparative genomics of parthenogenetic ant species.

genomics↗

bioRxiv2020

phiC31 integrase for recombination mediated single copy insertion and genome manipulation in C. elegans

C. elegans benefits from a large set of tools for genome manipulation. Yet, the insertion of large DNA constructs and the generation of inversions is still challenging. Here, we adapted the phiC31 integrase system for C. elegans. We generated an integrated phiC31 integrase expressing strain flanked by attP sites that also serves as a landing pad for integration of transgenes by recombination mediated cassette exchange (RCME). This strain is unc-119(-) so RMCE integrants can be produced simply by injection of a plasmid carrying attB sites flanking unc-119(+) and the gene(s) of interest. Additionally, phiC31 integrase is removed concomitantly with integration, eliminating the need to outcross away the integrase. Integrations are relatively easy to obtain for insert sizes up to ~15 kb. Taking advantage of this integration method we establish a dual color fluorescent operon reporter system to study post-transcriptional regulation of mRNA. Last we show that large chromosomal segments can be inverted using phiC31 integrase. Thus the phiC31 integrase system should be a useful addition to the C. elegans toolkit.

genetics↗