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Jeong, C.

Publications and source records attributed to Jeong, C..

At least 19 recordsLinked to original sources

The genomic basis of evolutionary stasis in the 500-million-year-old red seaweed genus Ahnfeltia

The red seaweed genus Ahnfeltia is an ancient lineage that has persisted for over 500 million years with remarkably limited diversification despite a global distribution in cold-temperate intertidal habitats. Compared to the highly diverse sister lineage, Rhodymeniophycidae, Ahnfeltia provides a unique system for investigating long-term evolutionary persistence in marine macroalgae. Here, we generated chromosome-scale genomes from five populations across three species and combined population genomics with paleogeographic niche modelling. Our results reveal remarkable genomic conservation, strong geographic isolation with limited gene flow, high homozygosity, and evidence of purifying selection. Niche projections indicate long-term stability and spatial connectivity of suitable cold-temperate habitats. These findings suggest that Ahnfeltias persistence and limited diversification are linked to genomic constraints and stable ecological niches over geological timescales. This study provides new insights into the genomic basis of evolutionary stasis in ancient marine lineages and highlights potential vulnerability to ongoing climate change affecting cold-water coastal ecosystems.

evolutionary biology↗

Direct RNA Sequencing reveals epitranscriptomic regulation of brain cells and Alzheimer's Disease pathology

Alternative mRNA splicing and post-transcriptional RNA modification are key mechanisms that regulate transcript function; however, their role in neuronal activity and neurodegenerative disease remains poorly defined. In this study, we evaluated two nanopore-based long-read sequencing (LR-seq) formats: cDNA-PCR sequencing (CPS) and direct RNA sequencing (DRS). We then applied DRS to profile both full-length isoforms and RNA modifications in major brain cell types derived from induced pluripotent stem cells (iPSCs) and post-mortem Alzheimers disease (AD) brains. Relative to CPS, DRS achieved higher accuracy and sensitivity for transcript quantification, de novo transcript model construction, and open reading frame (ORF) annotation across neuropathological gene sets. Focusing on iPSC-derived neurons, we built a multi-omic atlas to connect transcriptional output with translational engagement and protein abundance, by integrating DRS-based mRNA abundance, N6-methyladenosine (m6A) status and poly(A) tail length with ribosome profiling (Ribo-seq) and mass spectrometry (MS). The combination of DRS and Ribo-seq data demonstrated synergism in predicting protein abundance. This analysis also uncovered a significant inverse relationship between m6A modification and mRNA abundance, which was dependent on the engagement of the ribosomal A-site. Lastly, we applied DRS to the epitranscriptomic analysis of AD brain samples, demonstrating that m6A profiles can be used to distinguish early-versus late-stage disease.

neuroscience↗

Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling

AbstractParkinsons disease (PD) is commonly associated with dysfunctional mitochondrial homeostasis. PINK1, a S/T kinase mutated in early-onset PD, generates phosphoserine 65 ubiquitin (pS65Ub) on damaged mitochondria facilitating their removal. Here, we show that pS65Ub translocates into the nucleus after generation at damaged mitochondria and is directly attached to substrates by resident E3 ligases. Histone H2A is a major substrate and is modified at lysine 119 (H2AK119) by the polycomb silencer, E3 ligase RING1B. At nucleosomes, pS65Ub simultaneously suppresses RING1B and potentiates H2A deubiquitinases USP16 and USP21. Epigenetic profiling and RNA sequencing reveal that pS65Ub is enriched at the promoters of poorly expressed yet dynamically regulated genes and is associated with H2AK119ub depletion. Functionally, we show that pS65Ub enrichment drives polycomb target gene expression, which accelerates the maturation of dopaminergic neurons. Importantly, post-mortem PD brains exhibit elevated nuclear pS65Ub, potentially linking nuclear pS65Ub accumulation with disease pathogenesis. Together, these data indicate that pS65Ub generated at damaged mitochondria regulates fundamental cellular processes at distant sites.

cell biology↗

Deep Plasma Proteomics Coupled with Functional Genomics Reveals Drivers of Parkinson's Disease Progression and Levodopa Response

Parkinsons disease (PD) is a progressive neurodegenerative disorder lacking disease-modifying therapies, and its clinical management is limited by the absence of accessible biomarkers for tracking disease progression and treatment response. To map these complex disease trajectories, we implemented an ultra-deep plasma proteomics workflow integrating Mag-Net extracellular vesicle enrichment with Orbitrap Astral mass spectrometry to profile longitudinal samples from PD patients. This approach quantified 6,481 plasma proteins at unprecedented depth in PD studies, revealing distinct signatures directly associated with disease duration and dopaminergic therapy exposure. Candidate biomarkers were subsequently validated in an independent cohort using ELISA, demonstrating robust predictive utility in AI-driven prediction models. To uncover the mechanistic drivers underlying these systemic changes, we intersected our proteomic data with novel proteome-wide gene overexpression perturbation screens designed to identify regulators of alpha-synuclein pre-formed fibril (PFF) uptake and PFF-induced neuronal toxicity. Finally, an integrative network analysis combining three independent proteome-wide assays revealed that key pathological hubs, such as CD14, IFNG, and PLAT, are targets of currently approved pharmacological agents. Collectively, these findings provide a comprehensive, systems-level map for PD biomarker discovery and highlight druggable pathways to advance precision medicine strategies.

neuroscience↗

PAF15 stabilizes PCNA on DNA and slows down its sliding dynamics

The PCNA-associated factor 15 (PAF15) protein is essential for human genome stability by regulating DNA replication and repair through its interaction with proliferating cell nuclear antigen (PCNA). Despite its significance, the mechanistic details of the PAF15-PCNA interaction remain insufficiently understood. Here, we reveal how PAF15 influences the sliding dynamics and function of PCNA. Using single-molecule diffusion analysis on a DNA skybridge platform, we show that PAF15 binding stabilizes PCNA in its DNA-bound state, reduces its diffusion rate along the duplex, restricts accessibility to PCNA PIP-box binding sites, and regulates PCNA loading and unloading on DNA via replication factor C (RFC). Our results are consistent with its coordinating role in both high-fidelity replication and lesion bypass. These findings establish PAF15 as a key regulator of PCNA function, serving as a mobile platform for DNA-editing enzymes and thereby influencing genome maintenance.

biophysics↗

Population genomics of the endangered scaly-foot snail defines conservation units amid deep-sea mining threats in Indian Ocean vents

Hydrothermal vents in the Indian Ocean face imminent deep-sea mining, yet lack baseline high-resolution connectivity data for their endemic fauna. We present the first population genomic study of the endangered scaly-foot snail (Chrysomallon squamiferum), an iconic species distributed across three vent biogeographic provinces. Analysing 125 individuals from eight vent fields using 14 million single-nucleotide polymorphisms, we identify five genetic groups that warrant recognition as evolutionarily significant units. Demographic modelling reveals critical contributions from extinct or unsampled phantom populations to the contemporary genetic structure. Together with physical ocean modelling, we show that the deep currents drive asymmetric south-to-north gene flows, while transform faults act as dispersal barriers. We propose Longqi-Duanqiao fields on the Southwest Indian Ridge and Wocan field on the Carlsberg Ridge as two isolated populations prioritised for protection. Given its exceptional adaptations, wide distribution, and public recognition, the scaly-foot snail is well-positioned to serve as both a flagship and umbrella species to ensure the survival of a broader suite of vent biodiversity. As the International Seabed Authority finalises its Mining Code in 2025, our findings provide essential genomic evidence to mitigate the impacts of mining on genetic diversity and inform transboundary conservation strategies for this vulnerable ecosystem.

ecology↗

A deep population stratification and ongoing local adaptations of the range-expanding lovebug Plecia longiforceps

Rapidly range-expanding species provide a superb opportunity to study dynamic demography and ongoing adaptations to novel environments. Plecia longiforceps, a species of lovebug flies native to southeast China and Taiwan, has recently been expanding in Okinawa in Japan and Seoul in South Korea, where massive outbreaks are garnering public attention. Here we analyzed whole-genome sequences of 150 individuals across China, Korea, Okinawa, and Taiwan, including a newly identified northern Chinese population from Qingdao. We found a deep divergence between continental (Korea-China) and insular (Okinawa-Taiwan) populations and specify northern China and Taiwan as sources for Korea and Okinawa, respectively. Severely reduced genetic diversity in Korea and Qingdao suggests serial founder events during their northward expansion. An old split time between Qingdao and Korea ([~]3,500 generations ago) and multiple gene flows into Qingdao reject a simple scenario of a single recent northward migration. Selection signals in northern groups include genes associated with pigmentation, thermal sensing, lipid metabolism, and immunity. We observed a markedly reduced genetic diversity on X chromosome in northern populations, indicating ongoing strong sex-biased selection. Our findings portrait details of the northward range expansion in the species and highlight the role of adaptation for successful invasion at higher latitudes.

evolutionary biology↗

Bronze Age Yersinia pestis genome from sheep sheds light on hosts and evolution of a prehistoric plague lineage

Most human pathogens are of zoonotic origin. Many emerged during prehistory, coinciding with domestication providing more opportunities for spillover from original host species. However, we lack direct evidence linking past animal reservoirs and human infections. Here we present a Yersinia pestis genome recovered from a 3rd millennium BCE domesticated sheep from the Eurasian Steppe belonging to the Late Neolithic Bronze Age (LNBA) lineage, until now exclusively identified in ancient humans across Eurasia. We show that this ancient lineage underwent ancestral gene decay paralleling extant lineages, but evolved under distinct selective pressures contributing to its lack of geographic differentiation. We collect evidence supporting a scenario where the LNBA lineage, unable to efficiently transmit via fleas, spread from an unidentified reservoir to humans via sheep and likely other domesticates. Collectively, our results connect prehistoric livestock with infectious disease in humans and showcase the power of moving paleomicrobiology into the zooarcheological record.

genetics↗

DNA Hanger: Surface Free Single-Molecule Blotting Platform

Immunoblotting typically requires protein immobilization onto a membrane surface for quantification. Particularly, in real-time single-molecule blotting, stringent surface passivation is essential to prevent false-positive signals from nonspecific binding. In this study, we introduce a novel surface-free single-molecule blotting platform, termed the DNA Hanger. This platform employs a 3D structure of a quartz slide. Modified{lambda} -phage DNA molecules are randomly biotinylated along their bases and suspended between 4 m-high thin barriers, positioned away from the quartz slide surface. A light sheet, produced within the 3D structure, illuminates fluorophore-conjugated proteins bound to the biotinylated DNA, enabling single-molecule detection. The DNA Hanger assay significantly reduces nonspecific binding and enhances sensitivity to sub-picomolar concentrations, suggesting that this platform provides a novel, surface-condition-independent, and real-time approach in a wide range of single-molecule blotting.

biophysics↗

Extracellular Vesicle-Mediated Delivery of HIF1a Reprograms Macrophages for resolutive response in Sepsis

In sepsis, the liver functions as a central filter organ, where hepatic macrophages form a primary antimicrobial defense layer by eliminating bacteria and regulating immune responses. Therefore, precise regulation of the immune response in hepatic macrophages is crucial for triggering effective defense mechanisms. We aim to modulate the defense immune response by delivering transcription factor HIF1, a key regulator of monocyte/macrophage reprogramming in sepsis. Transcription factors are promising candidates because they dynamically modulate gene expression across diverse conditions, though delivering them remains challenging. In this study, we suggest a novel method for loading HIF1 into extracellular vesicles (EVs) to enhance immune defense and resolve sepsis. By delivering HIF1 to macrophages during sepsis, we promoted the differentiation of Nr1h3-dependent pro-efferocytic MoMFs and C/ebp{beta}-dependent pro-survival MoMFs. Pro-efferocytic MoMFs eliminate damaged hepatocytes and immune cells and pro-survival MoMFs withstand inflammatory conditions and trigger innate memory responses. Particularly, the zonation of these macrophages in the periportal region ensures effective pathogen clearance and minimizes tissue damage. These findings suggest that EV-mediated HIF1 delivery could be a promising therapeutic option for managing sepsis.

bioengineering↗

Reconstructing the genetic relationship between ancient and present-day Siberian populations

Human populations across a vast area in northern Eurasia, from Fennoscandia to Chukotka, share a distinct genetic component often referred to as the Siberian ancestry. Most enriched in present-day Samoyedic-speaking populations such as Nganasans, its origins and history still remain elusive despite the growing list of ancient and present-day genomes from Siberia. Here we reanalyze published ancient and present-day Siberian genomes focusing on the Baikal and Yakutia, resolving key questions regarding their genetic history. First, we show a long-term presence of a unique genetic profile in southern Siberia, up to 6,000 years ago, which distinctly shares a deep ancestral connection with Native Americans. Second, in the Baikal we find no direct contribution of the Early Neolithic Kitoi people to Late Neolithic and Early Bronze Age Serovo-Glazkovo ones. Third, the Middle Neolithic individual from Yakutia, belonging to the Belkachi culture, serves as the best source so far available for the spread of the Siberian ancestry into Fennoscandia and Greenland. These findings shed light on the genetic legacy of the Siberian ancestry and provide insights into the complex interplay between different populations in northern Eurasia throughout history.

genomics↗

Genomic detection of a secondary family burial in a single jar coffin in early Medieval Korea

ObjectivesFamily relationship is a key to understand the structure of past societies but its archaeological reconstruction mostly stays circumstantial. Archaeogenetic information, especially genome-wide data, provide an objective approach to accurately reconstruct the familial relationship of ancient individuals, thus allowing a robust test of an archaeology-driven hypothesis of kinship. In this study, we applied this approach to disentangle the genetic relationship of early Medieval individuals from Korea, who were secondarily co-buried in a single jar coffin. Materials and MethodsWe obtained genome-wide data of six early Medieval Korean individuals from a jar coffin. We inferred the genetic relatedness between these individuals and characterized their genetic profiles using well-established population genetics methods. ResultsCongruent with the unusual pattern of multiple individuals in a single jar coffin, genome-wide analysis of these individuals shows that they form an extended family, including a couple, their two children and both paternal and maternal relatives. We show that these early Medieval Koreans have a genetic profile similar to present-day Koreans. DiscussionWe show that an unusual case of a secondary multiple burial in a single jar coffin reflects family relationship among the co-buried individuals. We find both paternal and maternal relatives coburied with the nuclear family, which may suggest a family structure with limited gender bias. We find the genetic profile of early Medieval Koreans similar to that of present-day Koreans, suggesting no substantial genetic shift in the Korean peninsula for the last 1,500 years. Research HighlightsO_LIAncient genome-wide data find a family buried together in a jar coffin in early Medieval Korea. C_LIO_LIThese early Medieval Koreans have a genetic profile similar to present-day Koreans. C_LI

genomics↗

Optical regulation of endogenous RhoA reveals switching of cellular responses by signal amplitude

How protein signaling networks respond to different input strengths is an important but poorly understood problem in cell biology. For example, the small GTPase RhoA regulates both focal adhesion (FA) growth or disassembly, but whether RhoA serves as a switch selecting between cellular outcomes, or if outcomes are simply modulated by additional factors in the cell, is not clear. Here, we develop a photoswitchable RhoA guanine exchange factor, psRhoGEF, to precisely control endogenous RhoA activity. We also develop a FRET-based biosensor to allow visualization of RhoA activity together with psRhoGEF control. Using these new optical tools, we discover that low levels of RhoA activation preferentially induce FA disassembly in a Src-dependent manner, while high levels induce both FA growth and disassembly in a ROCK-dependent manner. Thus, rheostatic control of RhoA activation with photoswitchable RhoGEF reveals that cells can use signal amplitude to produce multiple responses to a single biochemical signal.

bioengineering↗

A dynamic 6,000-year genetic history of Eurasia's Eastern Steppe

The Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the regions population history. Here we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher Eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

genomics↗

Genomic and dietary transitions during the Mesolithic and Early Neolithic in Sicily

Southern Italy is a key region for understanding the agricultural transition in the Mediterranean due to its central position. We present a genomic transect for 19 prehistoric Sicilians that covers the Early Mesolithic to Early Neolithic period. We find that the Early Mesolithic hunter-gatherers (HGs) are a highly drifted sister lineage to Early Holocene western European HGs, whereas a quarter of the Late Mesolithic HGs ancestry is related to HGs from eastern Europe and the Near East. This indicates substantial gene flow from (south-)eastern Europe between the Early and Late Mesolithic. The Early Neolithic farmers are genetically most similar to those from the Balkan and Greece, and carry only a maximum of [~]7% ancestry from Sicilian Mesolithic HGs. Ancestry changes match changes in dietary profile and material culture, except for two individuals who may provide tentative initial evidence that HGs adopted elements of farming in Sicily. One-sentence summaryGenome-wide and isotopic data from prehistoric Sicilians reveal a pre-farming connection to (south-) eastern Europe, and tentative initial evidence that hunter-gatherers adopted some Neolithic aspects prior to near-total replacement by early farmers.

genetics↗

CoproID predicts the source of coprolites and paleofeces using microbiome composition and host DNA content

Shotgun metagenomics applied to archaeological feces (paleofeces) can bring new insights into the composition and functions of human and animal gut microbiota from the past. However, paleofeces often undergo physical distortions in archaeological sediments, making their source species difficult to identify on the basis of fecal morphology or microscopic features alone. Here we present a reproducible and scalable pipeline using both host and microbial DNA to infer the host source of fecal material. We apply this pipeline to newly sequenced archaeological specimens and show that we are able to distinguish morphologically similar human and canine paleofeces, as well as non-fecal sediments, from a range of archaeological contexts.

microbiology↗

Late Pleistocene human genome suggests a local origin for the first farmers of central Anatolia

Anatolia was home to some of the earliest farming communities. It has been long debated whether a migration of farming groups introduced agriculture to central Anatolia. Here, we report the first genome-wide data from a 15,000-year-old Anatolian hunter-gatherer and from seven Anatolian and Levantine early farmers. We find high genetic continuity ([~]80-90%) between the hunter-gatherer and early farmers of Anatolia and detect two distinct incoming ancestries: an early Iranian/Caucasus related one and a later one linked to the ancient Levant. Finally, we observe a genetic link between southern Europe and the Near East predating 15,000 years ago that extends to central Europe during the post-last-glacial maximum period. Our results suggest a limited role of human migration in the emergence of agriculture in central Anatolia.

genetics↗

Characterizing the genetic history of admixture across inner Eurasia

The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report genome-wide data of two Eneolithic individuals ({bsim}5,400 years before present) associated with the Botai culture in northern Kazakhstan. We find that inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries. This genetic separation is well mirrored by geography. The ancient Botai genomes suggest yet another layer of admixture in inner Eurasia that involves Mesolithic hunter-gatherers in Europe, the Upper Paleolithic southern Siberians and East Asians. Admixture modeling of ancient and modern populations suggests an overwriting of this ancient structure in the Altai-Sayan region by migrations of western steppe herders, but partial retaining of this ancient North Eurasian-related cline further to the North. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.

genomics↗