Biology subjects

Yu, E.

Publications and source records attributed to Yu, E..

At least 19 recordsLinked to original sources

bioRxiv2026

DTCAMD, a disease-associated truncated form of CRYAB in neovascular age-related macular degeneration: a potential driver of subretinal fibrosis

Abstract Purpose: Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (nAMD) and remains poorly controlled by anti-vascular endothelial growth factor (VEGF) therapy. We investigated the role of B-crystallin (CRYAB) in angiogenic and fibrotic pathology and evaluated disease-associated CRYAB truncation as a therapeutic target. Methods: Aqueous humor from patients with nAMD was analyzed by quantitative proteomics and receiver operating characteristic (ROC) analysis. CRYAB function was assessed using knockout and knockdown approaches in a choroidal neovascularization (CNV) mouse model. CRYAB truncation and associated proteins were examined by immunoblotting, co-immunoprecipitation, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). C-terminal truncation was further examined in mouse retinal tissue using antibodies generated against full-length CRYAB and its C-terminal region. Primary human retinal pigment epithelial (hRPE)-THP-1 co-cultures were used to examine CRYAB truncation under fibrosis-associated conditions. Pharmacological effects were tested using ({+/-})-threo-3-methylglutamic acid (T3MG) and 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF). Results: CRYAB was upregulated in the aqueous humor of patients with nAMD. Higher CRYAB levels were associated with persistent lesions after initial anti-VEGF treatment. CRYAB knockout or knockdown reduced CNV pathology and decreased VEGFA and -smooth muscle actin (SMA) expression, without a significant substrain effect between C57BL/6N and C57BL/6J mice. A Ser45-phosphorylated truncated CRYAB species was detected in mouse laser-induced CNV model. We termed this species disease-associated truncated CRYAB in AMD (DTCAMD). Peptide mapping showed reproducible loss of distal C-terminal peptide coverage in truncated CRYAB. Consistent with this finding, C-terminal antibody recognition was reduced in CNV lesions. In hRPE-THP-1 co-cultures, DTCAMD accumulated with increased SMA expression. Proteomic analysis identified Prss1 as a candidate CRYAB-associated serine protease linked to truncation under CNV conditions. T3MG and AEBSF reduced DTCAMD-associated signals and CNV pathology. Conclusions: CRYAB contributes to angiogenic and fibrotic pathology in CNV. Disease-associated CRYAB truncation, particularly Ser45-phosphorylated DTCAMD, represents a potential therapeutic target for fibrotic remodeling in nAMD.

pathology↗

bioRxiv2026

A Saturated Aminotriester Lipid Enhances Amonafide Activity in Human Colorectal Cancer Cells

The delivery of small-molecule therapeutics across cellular membranes remains a fundamental challenge in drug development, particularly for compounds whose physicochemical properties limit intracellular bioavailability. Inspired by the low toxicity, biodegradability, and synthetic accessibility of triethanolamine-derived lipids, we investigated a series of C18 aminotriester lipids as excipients for the codelivery of anticancer therapeutics. Four structurally related triester lipids bearing saturated, cis-monounsaturated, trans-monounsaturated, and di-unsaturated C18 tails were synthesized through straightforward esterification reactions with triethanolamine. These lipids were evaluated for their ability to enhance the antiproliferative activity of several anticancer agents, including paclitaxel, doxorubicin, amonafide, homoharringtonine, camptothecin, and SN-38. Across multiple drug classes, the aminotriester lipids exhibited minimal intrinsic cytotoxicity and generally produced limited enhancement of drug potency. However, the fully saturated tris-stearate aminotriester lipid selectively enhanced the antiproliferative activity of amonafide in HCT-116 colorectal cancer cells, particularly at lower concentrations. In contrast, unsaturated lipid analogues displayed negligible enhancement effects, and the activity of the tris-stearate lipid was substantially attenuated in A549 lung adenocarcinoma cells, weakly observed in HT-29 colorectal cancer cells, and absent in CT26 murine colorectal cancer cells. Lactate dehydrogenase release assays indicated that these effects were not associated with membrane lysis or nonspecific cytotoxicity. Further, fluorescence microscopy time course experiments suggest improved membrane trafficking of amonafide when codelivered stoichiometrically with fully saturated C18 aminotriester lipids. Collectively, these findings demonstrate that saturated triethanolamine-based aminotriester lipids may function as selective and biocompatible codelivery excipients for certain small-molecule therapeutics. The observed dependence on both lipid saturation state and cellular context suggests that membrane organization and lipid packing may play important roles in mediating these effects. These results establish a foundation for further mechanistic investigations into aminotriester lipid-assisted small-molecule delivery systems.

cancer biology↗

bioRxiv2026

Expansion Revealing of Pathology Resolves Nanostructures Associated with Inflammatory Phenotypes in COVID-19 Decedent Human Brain Tissue

Expansion revealing (ExR) elucidates cellular organization by separating proteins within dense nanostructures by 20x linear expansion, but requires fixation procedures incompatible with human pathology specimens. Here, we report ExR of pathology (ExRPath), which attains [~]20 nm resolution and decrowding of such tissues, through iterative 20x expansion, adapted to human brain pathology specimens. We also report a single-shot 15x expansion protocol for such tissues (15ExMPath), achieved through one-shot 15x expansion. Applying ExRPath and 15ExMPath to COVID-19-decedent brain tissue reveals periodic amyloid nanoclusters that co-localize with SARS-CoV-2 in a rare minority of patient specimens, pointing to a potential neuroinflammatory phenotype associated with COVID-19, and highlighting the power of high-throughput nanoimaging, empowered by expansion microscopy, for discovering potential novel disease mechanisms.

neuroscience↗

bioRxiv2026

Disrupted Sleep-Dependent Neural Oscillations and Transcriptomic Changes in the Cacna1g Loss-of-Function Mouse Model Implicated in Schizophrenia

Sleep is an essential biological process for maintaining brain function, and impaired sleep microarchitecture is a well-established feature of schizophrenia (SCZ). Rare loss-of-function variants in CACNA1G, encoding the T-type calcium channel CaV3.1, confer substantial risk for SCZ, implicating sleep-regulatory circuits in disease pathophysiology. Here, we first show that among individuals with SCZ, carriers of rare CACNA1G missense variants exhibit more pronounced alterations in sleep neurophysiology than non-carriers, identifying a human phenotype suggestive of altered channel function. Motivated by this observation, we examined the consequences of Cacna1g loss of function in mice. Cacna1g deficiency produced profound disruptions in sleep microarchitecture, including reduced sleep spindles, altered slow oscillations, impaired spindle-slow oscillation coupling, and reduced cortical synchrony--closely recapitulating neurophysiological signatures observed in individuals with schizophrenia. Beyond sleep structure, Cacna1g loss disrupted the normal coordination of brain rhythms across the 24-hour cycle, most notably abolishing diurnal modulation of theta oscillations. At the molecular level, Cacna1g loss uncoupled sleep-wake state from gene and protein regulation, producing widespread, sleep-phase-biased transcriptional and synaptic alterations across brain regions and cell types, particularly in cortical excitatory neurons. These network and molecular disruptions were accompanied by behavioral hyperactivity during the active phase. Together, these findings establish CACNA1G/CaV3.1 as a key regulator linking sleep-dependent brain dynamics to molecular homeostasis and behavior, and provide a mechanistic framework through which genetic risk for SCZ may drive disease-relevant sleep and circuit dysfunction. One Sentence SummaryLoss of CACNA1G disrupts sleep rhythms and gene regulation, creating a mismatch between brain state and behavior linked to schizophrenia.

neuroscience↗

bioRxiv2026

Dual Engram Architecture within a Single Striatal Cell Type Distinctly Controls Alcohol Relapse and Extinction

Relapse is a major obstacle in the treatment of alcohol and drug addiction and is thought to be driven by persistent drug-associated memories formed during their use. Behavioral therapies such as extinction training can reduce relapse and are proposed to work by creating a competing memory trace. However, where and how these opposing memories are stored in the brain is unknown. Here, we show that two anatomically and functionally distinct engram ensembles within the same genetically defined striatal cell type, direct-pathway medium spiny neurons (dMSNs), encode these opposing memories. Using engram-tagging tools in mice, we found that the acquisition of operant alcohol learning recruits a dMSN ensemble enriched in the striatal matrix compartment that stores alcohol-associated memories and whose activation selectively promotes relapse. Conversely, extinction of alcohol seeking recruits a dMSN ensemble enriched in the striosome compartment that stores extinction-related memories and whose activation suppresses relapse. Furthermore, we reveal that the physical memory trace storing the relapse-promoting memory is embedded within persistently strengthened corticostriatal synapses engaged during learning, and that artificially reproducing this plasticity is sufficient to trigger relapse-like behavior. These findings uncover a dual-engram architecture within dMSNs that governs relapse and extinction, providing a mechanistic framework for understanding how competing memories regulate drug-seeking behavior. HighlightsO_LIAcquisition and extinction of alcohol learning recruits distinct dMSN ensembles. C_LIO_LIAcquisition recruits matrix-enriched dMSN ensembles to promote relapse. C_LIO_LIExtinction recruits striosome-enriched dMSN ensembles to suppress relapse. C_LIO_LIEngram dMSNs show lasting synaptic potentiation and mimicking this potentiation triggers relapse. C_LI

neuroscience↗

bioRxiv2025

Engineering chimeric DNA polymerases for DNA movable type storage

DNA-based information storage offers a promising alternative to conventional media due to its high density, long-term stability, and low energy requirements. However, its application remains hindered by synthesis costs, limited sequence length and poor scalability. DNA polymerase is a critical enzymatic tool in the DNA storage systems by enabling high-fidelity data writing and targeted sequence amplification. In this study, we engineered chimeric DNA polymerases by fusing the high-fidelity 9{degrees}N DNA polymerase with double-stranded DNA binding proteins derived from thermophilic archaea. These fusions significantly enhanced processivity, thermal stability, and salt tolerance by stabilizing enzyme-template interactions, mimicking sliding clamps while preserving catalytic efficiency. Leveraging these properties, we demonstrated precise file retrieval from a mixed oligonucleotide pool using orthogonal barcode primers. Compared with wild-type 9{degrees}N, the chimeric polymerases, particularly PLS, exhibited reduced substitution error rates and improved read accuracy. We then applied these enzymes to a DNA movable type storage system, where prefabricated DNA modules were assembled into encoding blocks. Using engineered polymerases, these blocks were recombined to enable flexible data rewriting without de novo DNA synthesis. Moreover, a multi-enzyme assembly strategy enabled the construction of kilobase-scale DNA sequences encoding a classical Chinese poem, achieving complete data recovery. All assembled fragments remained stable in E. coli over 100 generations, exhibiting the potential for in vivo storage. Collectively, our findings demonstrated the role of engineered DNA polymerases for DNA-based information storage. Moreover, this system reduced synthesis demands, supported scalable rewriting, and ensured long-term preservation, offering a practical route to sustainable, high-fidelity DNA data storage.

synthetic biology↗

bioRxiv2025

Rice Ethylene Receptors Function as Ca2+-Permeable Ion Channels to Orchestrate Calcium-Dependent Antagonism of Ethylene Responses in Roots

The gaseous phytohormone ethylene governs essential plant processes spanning development, productivity, and stress resistance. As an essential nutrient and second messenger, calcium (Ca2+) is widely implicated in diverse plant physiological activities; however, its role in the ethylene signal transduction pathway remains elusive. Here, we identified a calcium-dependent antagonism of ethylene response (CAER) specifically modulates root elongation in the model cereal rice (Oryza sativa). Interestingly, we demonstrate that the ethylene receptors OsERS1 and OsERS2 both function as Ca2+-permeable channels, with OsERS1 further acting as a non-selective cation channel capable of permeating both monovalent and divalent cations. Mutagenesis analysis reveals that OsERS1 channel activity relies on homomeric assembly sites (C4/C6) rather than its ethylene-binding site (C65), indicating a clear decoupling of the molecular modules governing receptor signaling and ion channel function. The loss-of-function mutant Osers1/2 does not exhibit the CAER phenotype of the wild type (WT), confirm that this calcium-dependent regulatory mechanism is dependent on both OsERS1 and OsERS2. These findings uncover an unexpected ion-channel function of ethylene receptors, redefining their molecular identity beyond canonical signaling proteins and establishing the novel "hormone receptor-type ion channel (HRIC)" paradigm--one that fundamentally expands our understanding of how plant hormones transduce signals at the membrane.

developmental biology↗

bioRxiv2025

Substrate stiffness and viscoelasticity influence fibroblast senescence

Senescent cell accumulation has been implicated in aging and fibrotic disease, which are both characterized by increased tissue stiffness. However, the direct connection between tissue mechanics and senescence induction remains disputed in the literature. Thus, this work investigates the influence of hydrogel stiffness and viscoelasticity in promoting fibroblast senescence both in combination with genotoxic stress and independently. We show that while lung fibroblast YAP signaling declines with senescence induction, senescent fibroblasts maintain their mechanosensing capabilities with increased YAP nuclear localization on higher stiffness hydrogels. Most notably, we find a unique role for hydrogel viscoelasticity in senescence induction with soft (2 kPa) viscoelastic substrates promoting both the onset and amplification of senescence, even in the absence of genotoxic stress. These changes are not associated with a decline in YAP activity, but instead with a decline in nuclear DAPI intensity, suggesting a role of nuclear organization in driving this phenotype. Overall, this work highlights the influence of mechanics on the induction of senescence and supports the key role of viscoelasticity.

bioengineering↗

bioRxiv2025

Genomic structural equation modeling of impulsivity and risk-taking traits reveals three latent factors distinctly associated with brain structure and development

BackgroundImpulsivity is a multifaceted transdiagnostic trait that emerges in childhood. Research has identified genetic loci and brain systems associated with different facets of impulsivity and risk-taking. However, how these genetic underpinnings overlap across different facets, and how they are associated with brain development during childhood remain unknown. MethodsUsing genomic structural equation modeling on 17 impulsivity and risk-taking traits, we identified latent factors capturing overlapping genetic architecture. We then calculated polygenic scores for these factors using Adolescent Brain Cognitive Development Study data (N = 4,142) and examined their associations with brain structure, development, and behavior in children aged 9-14 years. Finally, we tested whether socioeconomic status modulated the associations between latent polygenic scores and brain structures. ResultsWe identified three distinct genetic latent factors, which we label lack of self-control, reward drive, and sensation seeking. In children, polygenic scores for the three factors showed associations with distinct brain patterns: lack of self-control associated with reduced prefrontal cortical thickness, reward drive with increased subcortical cellular density, and sensation seeking with increased cortical surface area and white matter integrity. Longitudinally, lack of self-control predicted slower white matter development. The association between polygenetic score for lack of self-control and white matter mean diffusivity was modulated by socioeconomic status. ConclusionsWe identified three genetically distinct dimensions of impulsivity and risk-taking with separable neurodevelopmental origins. These genetic predispositions manifested as distinct brain patterns as early as ages 9-10. Environmental experience modulated some of the genetic effects on brain development.

neuroscience↗

bioRxiv2025

Synthetic derivatives of vinpocetine as antiproliferative agents

Vincamine is an indole alkaloid initially isolated from plants of the Vinca genus and has previously been demonstrated to have antioxidant, hypoglycemic, and hypolipidemic activities. Vinpocetine, a synthetic derivative of vincamine with an enhanced pharmacological profile, has demonstrated promising antiproliferative properties. While previously reported vinpocetine derivatives have undergone extensive investigation for their pharmacological properties, the role of the E-ring ethyl ester in the anticancer properties of compounds with this scaffold has not yet been fully described. Here, we report the antiproliferative activity of two vinpocetine analogs with modifications at the E-ring. MTT assays revealed that reduction of the ethyl ester to an alcohol exhibited strong dose-dependent antiproliferative activity across five mammalian cell lines, but did not induce significant markers of apoptosis or necrotic death as determined by FITC/Annexin V and cell cycle flow cytometry, respectively. We further observe that vinpocetine and both analogs exhibit dose-dependent modulation of a TCF/LEF reporter cell, which appears to be decoupled from trends in antiproliferative activity Altogether, this work demonstrates the potential for E-ring modifications of vinpocetine as anticancer agents.

cancer biology↗

bioRxiv2025

Artery-on-chip demonstrates smooth muscle function comparable to both healthy and diseased living tissues

Arterial diseases affect the mechanical properties of blood vessels, which then alter their function via complex mechanisms. To develop and test effective treatments, microphysiological systems replicating the function and mechanics of a human artery are needed. Here, we establish an artery-on-chip (ARTOC) using vascular derivatives of human induced pluripotent stem cells (iPSCs) cultured with pulsatile flow on an electrospun fibrin hydrogel. ARTOCs have mature, laminated smooth muscle that expresses robust extracellular matrix and contractile proteins, contracts in response to intraluminal pressure and vasoagonists, and exhibits tissue mechanics comparable to those of human small-diameter arteries. Using real-time monitoring of radial distention and luminal pressure to inform computational fluid dynamics modeling, we show that we can effectively tune biomechanical cues using fibrin scaffold thickness and luminal flow rate. We successfully tune these cues to promote the survival and function of both endothelial and smooth muscle cells simultaneously in the ARTOC. To test the ARTOC as a disease modeling platform, we first use non-isogenic iPSC-derived smooth muscle cells from a polycythemia patient, and we find significantly altered cell phenotype and increased vessel wall stiffness compared to controls. We then test a novel isogenic disease model in ARTOCs from iPSCs CRISPR-edited with the LMNA Hutchinson-Guilford Progeria Syndrome (LMNA G608G; LMNAHGPS) mutation. LMNAHGPS ARTOCs show extracellular matrix accumulation, medial layer loss, premature senescence, and loss of tissue elasticity and ductility. With this work, we establish the ARTOC as a platform for basic and translational studies of arterial diseases, bridging the current gap in linking protein expression and cell phenotype to tissue mechanics and function in small-diameter arteries.

bioengineering↗

bioRxiv2025

Associations between epilepsy-related polygenic risk and brain morphology in childhood

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres. Compared to disease-related effects derived from epilepsy case-control cohorts, structural correlates of PRS-HS mirrored atrophy and epicentre patterns in patients with TLE-HS. By identifying a potential pathway between genetic vulnerability and disease mechanisms, our findings provide new insights into the genetic underpinnings of structural alterations in TLE-HS and highlight potential imaging-genetic biomarkers for early risk stratification and personalized interventions.

neuroscience↗

bioRxiv2024

Astrocyte regional specialization is shaped by postnatal development

Astrocytes are an abundant class of glial cells with critical roles in neural circuit assembly and function. Though many studies have uncovered significant molecular distinctions between astrocytes from different brain regions, how this regionalization unfolds over development is not fully understood. We used single-nucleus RNA sequencing to characterize the molecular diversity of brain cells across six developmental stages and four brain regions in the mouse and marmoset brain. Our analysis of over 170,000 single astrocyte nuclei revealed striking regional heterogeneity among astrocytes, particularly between telencephalic and diencephalic regions, at all developmental time points surveyed in both species. At the stages sampled, most of the region patterning was private to astrocytes and not shared with neurons or other glial types. Though astrocytes were already regionally patterned in late embryonic stages, this region-specific astrocyte gene expression signature changed dramatically over postnatal development, and its composition suggests that regional astrocytes further specialize postnatally to support their local neuronal circuits. Across mouse and marmoset, we found hundreds of species differentially expressed genes, as well as divergence in the expression of astrocytic region- and age-differentially expressed genes and the timing of astrocyte maturation relative to birth between the species. Finally, we used expansion microscopy to show that astrocyte morphology is also regionally specialized across cortex, striatum, and thalamus in the mouse.

neuroscience↗

bioRxiv2024

Inhibition of pterygium cell fibrosis by the Rho kinase inhibitor

Pterygium is an ocular disease in which the conjunctival tissue invades the cornea. When the pterygium tissue reaches the pupillary region, the visual function of the patient is affected. Currently, surgical removal is the only effective treatment. However, the recurrence rate of pterygium after surgery can be high. Pterygium is also a health disparity issue since it is more prevalent in the Hispanic and Latino American population. In this study, we determined if the Rho kinase inhibitor can be used to prevent pterygium recurrence since its anti-fibrosis effects have been reported in other cell and tissue types. We cultured primary pterygium cells from pterygium tissues from Hispanic and Latino American, African American, Caucasian, and Asian donors, and used those cells for viability assays, scratch assays, migration assays, and immunostaining of F-actin, fibronectin, collagen I and smooth muscle actin. We found that the Rho kinase inhibitor Y27632 decreased cell viability, wound healing, cell migration, as well as the expression of extracellular matrix and myofibroblast markers in cultured pterygium cells. We believe that Rho kinases inhibitors are a potential post-surgical treatment to prevent pterygium recurrence.

pharmacology and toxicology↗

bioRxiv2024

Developmental variability in cotton fiber cell wall properties linked to important agronomic traits

The economic value of cotton is based on its long, thin, strong, and twisted trichoblasts that emerge from the ovule epidermis. The mature dried fiber cell reflects the outcome of a rapid tapering of the nascent trichoblast, weeks of polarized diffuse growth, followed by a transition to persistent secondary cell wall synthesis. Highly conserved and dynamic microtubule and cellulose microfibril-based anisotropic growth control modules are central to all of these phases. In this paper, we developed novel quantitative phenotyping and computational modeling pipelines to analyze fiber growth behaviors at a daily resolution. We uncovered unexpected variability in growth rate, cell wall properties, and cell geometry across a critical window of fiber development. Finite element computational modeling of fiber growth was used to analyze the instability of cell diameter control and predict how spatial gradients of fiber and matrix material properties can interact to dictate the patterns of shape change. As an initial step toward gaining insight into the molecular orchestration of cellulose biosynthesis, expression profiles of a broad set of relevant genes were quantified across the same developmental timeline and correlated with fiber phenotypes. This analysis identified specific candidate genes that may serve as targets for fiber quality improvement.

plant biology↗

bioRxiv2024

Genome-wide association study of glucocerebrosidase activity modifiers.

One of the most common genetic risk factors for Parkinsons disease (PD) are variants in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GCase deficiency has been associated with an increased PD risk, but not all individuals with low GCase activity are carriers of GBA1 mutations, suggesting other factors may be acting as modifiers. We aimed to discover common variants associated with GCase activity, as well as replicate previously reported associations, by performing a genome-wide association study using two independent cohorts: a Columbia University cohort consisting of 697 PD cases and 347 controls and the Parkinsons Progression Markers Initiative (PPMI) cohort consisting of 357 PD cases and 163 controls. As expected, GBA1 variants have the strongest association with decreased activity, led by p.N370S (beta = -4.36, se = 0.32, p = 5.05e-43). We also identify a novel association in the GAA locus (encoding for acid alpha-glucosidase, beta = -0.96, se = 0.17, p = 5.23e-09) that may be the result of an interaction between GCase and acid alpha-glucosidase based on various interaction analyses. Lastly, we show that several PD-risk loci are potentially associated with GCase activity. Further research will be needed to replicate and validate our findings and to uncover the functional connection between acid alpha-glucosidase and GCase.

genetics↗

bioRxiv2023

RealSeq2: a software integrated with UMI identification, error correction, and methylation modifications storing

High-throughput UMI technology sequencing is widely used in early tumor screening, detection, recurrence monitoring, etc. Detecting extremely low-frequency mutations is especially important for monitoring tumor recurrence, so high-precision data, as well as high-quality data, are required. We developed RealSeq2, a new integrated data-preprocessing software based on fastp and gencore, to achieve adapter removal, quality control, UMI identification, and generate consensus reads by clustering and error correction using multithreading in high-throughput next-generation sequencing background. RealSeq2 also supports methylation data of 5-methylcytosine bisulfite-free sequencing. RealSeq2 defined a new tag in SAM for storing methylation information, which is beneficial for co-identifying methylation sites and mutation sites for downstream analysis. RealSeq2 includes three submodules: ReadsProfiler, ReadsCleaner, and ReadsRecycler. In addition, the output format file (BAM or SAM) is universal for downstream analyses. RealSeq2 is the preferred upstream analysis software for the co-detection of ultra-low frequency mutations and bisulfite-free methylation data. The error profile provides data support for downstream analysis. Additionally, XM tags will become a standard protocol for recording methylation signals.

bioinformatics↗

bioRxiv2022

Genomic loss of the HSP70cA gene in the vertebrate lineage

Metazoan 70 kDa heat shock protein (HSP70) genes have been classified into four lineages: cytosolic A (HSP70cA), cytosolic B (HSP70cB), endoplasmic reticulum (HSP70er), and mitochondria (HSP70m). Because previous studies have identified no HSP70cA genes in vertebrates, we hypothesized that this gene has lost on the evolutionary path to vertebrates. To test this hypothesis, the present study conducted a comprehensive database search followed by phylogenetic and synteny analyses. The HSP70cA gene was present in invertebrates and animals that belong to subphyla of Chordata, Cephalochordata (lancelets) and Tunicata (tunicates). However, the genomes of early vertebrates in the subphylum Craniata (lamprey, hagfish, elephant shark, and coelacanth) contained only HSP70cB genes, suggesting the loss of the HSP70cA gene in the early period of vertebrate evolution. Synteny analysis using available genomic resources indicated that the synteny around the HSP70 genes was generally conserved between tunicates, but it was largely different between tunicates and lamprey. These results suggest the presence of dynamic chromosomal rearrangement in early vertebrates, which possibly caused the loss of the HSP70cA gene in the vertebrate lineage.

evolutionary biology↗