Biology subjects

Hirose, M.

Publications and source records attributed to Hirose, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Rabies virus antagonizes interferon signaling by targeting phosphorylated STAT1 tetramers

AO_SCPLOWBSTRACTC_SCPLOWRabies virus phosphoprotein (P protein) antagonizes interferon signalling by selectively targeting activated STAT1 protein, but the structural basis for the selective recognition of activated STAT1 has remained unclear. Here we report cryo-EM structures of tyrosine-phosphorylated STAT1 (pY-STAT1) in complex with the C-terminal domain of P protein (P-CTD). P-CTD engages the pY-STAT1 tetramer through three discrete interfaces, contacting two DNA-binding domains within a pY-mediated STAT1 dimer and the N-terminal domain of a third STAT1 protomer. This binding mode explains how P-CTD selectively recognizes activated STAT1, occludes surfaces required for importin 5 and DNA binding, and stabilizes the compact tetrameric state, thereby restricting the conformational transition required for cooperative DNA binding. Cell-based assays further indicate that distinct P-CTD surfaces differentially contribute to antagonism of type I and type II interferon signalling. Further, by acting as an anchoring molecule, P-CTD also enabled structural elucidation of the complete STAT1 structures in the tetramer. Together, these data reveal critical mechanisms in viral immune evasion and pathogenesis, and fundamental innate immune signaling.

molecular biology↗

bioRxiv2026

A novel periplasmic layer formed by an outer membrane lipo-protein governs the cell-envelope integrity and stiffness of Leptospira interrogans

The structural integrity and mechanical properties of the cell envelope are crucial for bacterial physiology and dynamics; however, how specific molecular components govern these properties remains poorly understood. Here, we report the novel structural and mechanical functions of LipL32, the most abundant outer-membrane (OM) lipoprotein in the pathogenic spirochete Leptospira interrogans. LipL32 accounts for approximately 75% of the total OM proteins, yet its functional role has remained enigmatic. Cryo-electron microscopy revealed that the highly dense LipL32 forms a hitherto unappreciated thin layer in the periplasmic space, positioned adjacent to the peptidoglycan (PG) layer. The structural analysis also demonstrates that the disruption of lipL32 by transposon insertion results in irregular deformation of OM and spatial variability in the width of the periplasmic space. Quantitative measurements by optical tweezers confirmed that the lipL32::Tn mutant exhibited a significant reduction in whole-cell stiffness. Consistent with this mechanical impairment, the lipL32::Tn mutant displayed a diminished ability to penetrate a heterogeneous agar mesh model that mimics the hosts extracellular matrix, suggesting an important role for cell rigidity in initial infection via damaged skin. These findings define LipL32 as a critical mechanical stabilizer that maintains the structural integrity of the cell envelope. This work provides a new paradigm for understanding how specialized lipoproteins contribute to bacterial cell mechanics, offering insights into pathogenic invasiveness.

microbiology↗

bioRxiv2026

Three-dimensional redistribution of pelagic fish aggregations associated with floating offshore wind farms

Floating offshore wind farms (F-OWFs) are rapidly expanding into offshore pelagic environments, yet their ecological consequences remain poorly resolved because quantitative, non-invasive monitoring is challenging at sea. Here, we integrated environmental DNA (eDNA) metabarcoding and scientific echosounding to assess fish community composition and three-dimensional aggregation structure around a commercial-scale F-OWF off the Goto Islands, Japan. We compared four stations adjacent to turbines with four offshore control stations under comparable environmental conditions across five sampling periods (April and August 2024; May, June, and August 2025) and three depth layers (5, 50, and 80-160 m). eDNA metabarcoding detected 126 fish species, and community structure based on the 30 most frequently detected taxa did not differ significantly between the F-OWF and control areas (Bray-Curtis PERMANOVA, p = 0.60). Species richness varied strongly with sampling period and water layer, with a significant water layer x period interaction, whereas overall richness did not differ between areas (Mann-Whitney U test, p = 0.18). In contrast, acoustic surveys revealed a marked difference in vertical structuring of fish aggregations: in the control area, NASC per mile increased with depth, while this depth-dependence disappeared near turbines. Moreover, the weighted mean normalized depth (WMND) indicated a shallower vertical center of aggregation in the F-OWF area (0.34) than in the control area (0.24), consistent with turbine-associated redistribution in the water column. Although voyage-level integrated NASC per mile did not differ significantly between areas (t-test, p = 0.83), mean values were higher near turbines. Together, these results indicate that F-OWFs can be associated with changes in the three-dimensional organization of fish aggregations without producing pronounced shifts in dominant taxonomic composition. Our study demonstrates the value of combining eDNA metabarcoding and acoustics for evaluating ecological effects of offshore renewable-energy infrastructures and provides a framework for standardized, long-term monitoring as F-OWF deployment accelerates globally.

ecology↗

bioRxiv2025

Tegmental atrophy in isolated REM sleep behaviour disorder: Ex vivo-informed in vivo imaging

Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is an early-stage synucleinopathy characterized by brainstem pathology. In rodents, the pontine tegmentum contains an REM sleep centre, the sublaterodorsal nucleus (SLD), which expresses corticotropin-releasing hormone binding protein (CRHBP). While the involvement of brainstem pathophysiology is thus implicated in iRBD, its solid evidence remains scarce in humans due to the difficulty in identifying small brainstem nuclei with conventional MRI technology alone. Here, we aimed to detect tegmental atrophy in iRBD with voxel-based morphometry (VBM) analysis combined with a novel human brainstem atlas. Structural MRIs from 98 patients with iRBD and 114 controls were analysed to investigate grey matter volume (GMV) using VBM. Our unique approach involved detailed assessments of the VBM results, guided by a high-resolution MRI-based atlas of the human brainstem. This brainstem atlas was founded on ex vivo MRI of 10 postmortem human specimens. We validated it with CRHBP immunostaining, which aided in identifying putative REM sleep-regulating nuclei in humans. We applied this brainstem atlas to identify atrophy in specific brainstem regions in iRBD and correlate their volumes with clinical measures, including autonomic functions. VBM revealed a focal cluster of grey matter atrophy in the dorsal pontine tegmentum of iRBD patients, including the laterodorsal tegmental nucleus, ventral part (LDTgV) and the pedunculopontine tegmental nucleus (PTg). Our atlas-based analysis confirmed the LDTgV as the site of most conspicuous atrophy, revealing a significant volume reduction in iRBD patients compared to controls with a moderate effect size (Cohens d = 0.46, Bonferroni-corrected p = 0.019). Furthermore, greater atrophy in the LDTgV and the PTg was associated with more severe autonomic dysfunction as measured by Scales for Outcomes in Parkinsons Disease-Autonomic dysfunction (SCOPA-AUT) scores (partial r = -0.237, p = 0.019 and partial r = -0.236, p = 0.019, respectively). Histological analysis confirmed that the LDTgV is selectively enriched with CRHBP-positive neurons, a putative marker for REM sleep-on neurons. We provided novel evidence for the involvement of LDTgV, the putative human homolog of the murine SLD, in iRBD. The present findings advance our understanding of the neuroanatomical basis of iRBD and will contribute to the development of early biomarkers for -synucleinopathies.

neuroscience↗

bioRxiv2025

Resf1 is required for proper placental development and configuration of trophoblast cell-specific heterochromatin

Resf1 (Retroelement silencing factor 1) is involved in retroelement silencing cooperated with H3K9 methyltransferase SETDB1 by regulating H3K9 methylation in mouse embryonic stem cells (mESCs). However, it remains unknown whether Resf1 functions in retroelement silencing in vivo, and has a role in development. Here, we established Resf1-deficient mice, which exhibited developmental delay, partial embryonic lethality, and placental defects. Notably, retroelements were also upregulated in the Resf1-deficient placenta, correlating with increased expression of nearby genes. To further assess whether Resf1 functions within the trophoblast lineage, we generated Resf1-deficient trophoblast stem cell (TSC) lines. Both undifferentiated TSCs and differentiated TSCs (D-TSCs) display increased retroelement expression along with elevated levels of genes associated with placental development. Moreover, Resf1-deficient TSCs exhibit compromised maintenance of H3K9me3 domains in a manner independent of SETDB1. Collectively, our findings reveal that Resf1 plays multifaceted roles beyond retroelement silencing, underscoring its importance in development and its critical function in trophoblast lineage regulation.

developmental biology↗

bioRxiv2025

Proteo-transcriptomic reprogramming and resource reallocation define the aging mammalian brain

Brain aging is a major risk for neurodegeneration, yet the underlying molecular mechanisms remain poorly understood. Here we performed an integrative proteo-transcriptomic analysis of the aging mouse brain, uncovering molecular signatures of aging through the assessment of protein aggregation, mRNA relocalization, and comparative proteomics across eight models of premature aging and neurodegeneration. We identified dynamic changes in physiological aging highlighting differences in synaptic maintenance and energy-allocation. These were linked to changes associated with fundamental protein biochemical properties such as size and net charge. Network analysis highlighted a decrease in mitochondrial complex I proteins not compensated at the mRNA level. Aggregation of 60S ribosome subunits indicated deteriorating translation efficiency and was accompanied by mitochondrial and proteasomal imbalance. The analysis of the nine models revealed key similarities and differences between physiological aging and pathology. Overall, our study provides an extensive resource on molecular aging, and offers insights into mechanisms predisposing to neurodegeneration, easily accessible at our Brain Aging and Molecular Atlas Project (BrainAging-MAP) website.

neuroscience↗

bioRxiv2025

Floating offshore wind farms cause Japanese horse mackerel to congregate

Floating offshore wind farms (F-OWFs) are becoming key components of renewable energy production, yet their ecological impacts on marine ecosystems remain largely unexplored. Using environmental DNA (eDNA) analysis in the East China Sea, this study investigated the tendency for Japanese horse mackerel (Trachurus japonicus) to congregate beneath F-OWFs. Water samples were collected at stations near an F-OWF and control stations farther away at various depths and seasons. A total of 115 samples were analyzed, and eDNA of T. japonicus was detected in 83% of all samples. eDNA concentrations were significantly higher near an F-OWF (F-OWF stations) than at control stations. The highest recorded eDNA concentration reached 2,280 copies/L at an F-OWF station, whereas the maximum concentration at control stations was 783 copies/L. Seasonal variations were also observed, with lower concentrations in summer and higher concentrations from autumn to spring. Generalized linear model (GLM) analysis further revealed that wind turbines had a significant influence on eDNA concentration, whereas other environmental variables, such as water temperature and depth, were not significant. These findings suggest that F-OWFs may function as artificial reefs, providing habitat for commercially important fish and influencing fish distributions at both spatial and temporal scales. However, potential conflicts with fisheries due to spatial restrictions, displacement of fishery resources, and increased navigation costs necessitate further long-term ecological and socio-economic assessments. Integrating eDNA monitoring with traditional survey methods, such as acoustic surveys and ROV observations, is crucial for coexistence of adaptive offshore wind farm management and sustainable fisheries. Future research should also explore the long-term effects of F-OWFs on fish assemblages and biodiversity to support evidence-based decision-making for offshore energy development.

ecology↗

bioRxiv2024

Structural insight into the nuclear transportation mechanism of PPARg by Transportin-1

The spatial and temporal control of protein is essential for normal cellular function. Proteins working in the nucleus have nuclear localization signal (NLS) sequences and are escorted into the nucleus by cognate nuclear transport receptors. A wealth of experimental data about NLS has been accumulated, and nuclear transportation mechanisms are established at the biochemical and structural levels. The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that control various biological responses. We recently reported that the transportation of PPAR{gamma} is mediated by Transportin-1, but PPAR{gamma} lacks a typical NLS sequence recognized by Transportin-1. Moreover, the recognition mechanism remains largely unknown. In this study, we determined the Cryo-EM structure of PPAR{gamma} in complex with Transportin-1 and revealed that Transportin-1 gripped the folded DNA binding domain and the Hinge region of PPAR{gamma}, indicating that PPAR{gamma} recognizes a folded domain with an extended region as a nuclear localization signal, not a canonical unstructured signal sequence, confirmed by the mutation analyses in vitro and in cultured cells. Our study is the first snapshot structure working in nuclear transportation, not in transcription, of PPAR{gamma}.

molecular biology↗

bioRxiv2024

Fc-independent SARS-CoV-2 infection-enhancing antibodies decouple N-terminal and receptor-binding domains by cross-linking neighboring spikes

Antibody dependent enhancement (ADE) is a serious concern in vaccine development. The canonical ADE pathways are dependent on the fragment crystallizable (Fc) region of the antibody. In SARS-CoV-2 several antibodies have been discovered that inflict ADE in vitro. These antibodies target the N-terminal domain (NTD) of the SARS-CoV-2 spike protein. We previously proposed that these NTD-targeting infection-enhancing antibodies (NIEAs) cross-link neighboring spike proteins via their NTDs, and that this results in a decoupling between the NTD and receptor binding domain (RBD), facilitating the "RBD down" to "up" transition. In this study we present a combination of molecular dynamics simulations and cryogenic electron microscopy data that, together, demonstrate that NIEAs are indeed able to cross-link neighboring SARS-CoV-2 spike proteins, and that this cross-linking results in a decoupling of the NTD and RBD domains. These findings provide support for an Fc region independent ADE pathway that is not only relevant for SARS-CoV-2 but also for other viruses of which the spike proteins undergo a conformational change upon host cell entry.

molecular biology↗

bioRxiv2024

Structural insight into sodium ion pathway in the bacterial flagellar stator from marine Vibrio

Many bacteria swim in liquid or swarm on surface using the flagellum rotated by a motor driven by specific ion flow. The motor consists of the rotor and stator, and the stator converts the energy of ion flow to mechanical rotation. However, the ion pathway and the mechanism of stator rotation coupled with specific ion flow are still obscure. Here, we determined the structures of the Na+-driven stator of Vibrio, namely PomAB, in the presence and absence of sodium ions and the structure with its specific inhibitor, phenamil, by cryo-electron microscopy. The structures and following functional analysis revealed the sodium ion pathway, the mechanism of ion selectivity, and the inhibition mechanism by phenamil. We propose a model of sodium ion flow coupled with the stator rotation based on the structures. This work provides insights into the molecular mechanisms of ion specificity and conversion of the electrochemical potential into mechanical functions.

microbiology↗

bioRxiv2024

Structural analysis of S-ring composed of FliFG fusion proteins in marine Vibrio polar flagellar motors

The marine bacterium Vibrio alginolyticus possesses a polar flagellum driven by a sodium ion flow. The main components of the flagellar motor are the stator and rotor. The C-ring and MS-ring which are composed of FliG and FliF, respectively, are parts of the rotor. Here, we purified an MS-ring composed of FliF-FliG fusion proteins and solved the near-atomic resolution structure of the S-ring--the upper part of the MS-ring--using cryo-electron microscopy. This is the first report of an S-ring structure from Vibrio whereas, previously, only those from Salmonella have been reported. The Vibrio S-ring structure reveals novel features compared to that of Salmonella such as tilt angle differences of the core domain and the {beta}-collar region, the decrease of the inter-subunit interaction between core domains, and altered electrostatic inner-surface. The residues potentially interact with other flagellar components, such as FliE and FlgB, are well structurally conserved in Vibrio S-ring. These comparisons clarified the conserved and non-conserved structural features of the MS-ring across different species. IMPORTANCEUnderstanding the structure and function of the flagellar motor in bacterial species is essential for uncovering the mechanisms underlying bacterial motility and pathogenesis. Our study revealed the structure of the Vibrio S-ring, a part of its polar flagellar motor, and highlighted its unique features compared with the well-studied Salmonella S-ring. The observed differences in the inter-subunit interactions and in the tilt angles between the Vibrio and Salmonella S-rings highlighted the species-specific variations in the flagellar assembly. By concentrating on the region where the S-ring and the rod proteins interact, we uncovered conserved residues essential for the interaction. Our research contributes to advancing of bacterial flagellar biology.

biophysics↗

bioRxiv2024

Structural and Dynamic Insights into the Biased Signaling Mechanism of the Human Kappa Opioid Receptor

The {kappa}-opioid receptor (KOR) is a member of the G protein-coupled receptor (GPCR) family, responsible for modulating cellular responses through transducers such as G proteins and arrestins. G protein-biased KOR agonists hold promise due to their potential to mitigate side effects such as drug aversion and sedation while preserving analgesic and antipruritic effects. Here, we shed light on the structural dynamics of the human KOR-Gi signaling complex bound with either nalfurafine (a G-protein-biased agonist) or U-50,488H (a balanced agonist) using cryo-electron microscopy (cryo-EM). Cryo-EM structures of the KOR-Gi signaling complexes identify the ligand binding mode in the activated state. Vibrational spectroscopy analysis reveals changes in the ligand-binding pocket upon binding to these ligands. Cell-based mutant experiments pinpoint four amino acids (K2275.40, C2866.47, H2916.52, and Y3127.34; Ballesteros-Weinstein numbering is shown in superscript) that play crucial roles in arrestin recruitment. Among these four amino acids, H2916.52 and Y3127.34 are also implicated in G-protein coupling. Our findings pave the way for targeting specific residues in the KOR ligand-binding pocket to enhance KOR-mediated therapeutic effects while mitigating unwanted side effects.

biophysics↗

bioRxiv2023

Slitflow: a Python framework for single-molecule dynamics and localization analysis

Single-molecule imaging is a promising method for direct quantification of the dynamics and distribution of biomolecules in living cells. Although numerous methods have been developed to gain biological insights into molecular behavior, the high diversity of microscopes and single-molecule dynamics can result in incomplete reproducibility of analyses. Here, we present Slitflow, an open-source framework for a single-molecule analysis workflow that includes image processing, dynamics analysis, and figure creation. We demonstrated the integrity and flexibility of the workflow using 1) a cherry-picked tracking method combining popular tools and 2) various state-of-the-art analyses in a single pipeline. The software accommodates a large variety of data and methods, paving the way for integrative analyses. Code metadata O_TBL View this table: org.highwire.dtl.DTLVardef@1923125org.highwire.dtl.DTLVardef@d8790borg.highwire.dtl.DTLVardef@1f2f0ccorg.highwire.dtl.DTLVardef@9ee527org.highwire.dtl.DTLVardef@1d693f9_HPS_FORMAT_FIGEXP M_TBL C_TBL

biophysics↗

bioRxiv2023

An engineered ACE2 decoy broadly neutralizes Omicron subvariants and shows therapeutic effect in SARS-CoV-2-infected cynomolgus macaques

The Omicron variant continuously evolves under the humoral immune pressure obtained by vaccination and SARS-CoV-2 infection and the resultant Omicron subvariants exhibit further immune evasion and antibody escape. Engineered ACE2 decoy composed of high-affinity ACE2 and IgG1 Fc domain is an alternative modality to neutralize SARS-CoV-2 and we previously reported its broad spectrum and therapeutic potential in rodent models. Here, we show that engineered ACE2 decoy retains the neutralization activity against Omicron subvariants including the currently emerging XBB and BQ.1 which completely evade antibodies in clinical use. The culture of SARS-CoV-2 under suboptimal concentration of neutralizing drugs generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against engineered ACE2 decoy. As the efficient drug delivery to respiratory tract infection of SARS-CoV-2, inhalation of aerosolized decoy treated mice infected with SARS-CoV-2 at a 20-fold lower dose than the intravenous administration. Finally, engineered ACE2 decoy exhibited the therapeutic efficacy for COVID-19 in cynomolgus macaques. Collectively, these results indicate that engineered ACE2 decoy is the promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation can be considered as a non-invasive approach to enhance efficacy in the treatment of COVID-19.

microbiology↗

bioRxiv2022

OVGP1 is an oviductal fluid factor essential particularly for early embryonic development in golden hamsters

The mammalian oviductal lumen is a specialized chamber that provides an environment that strictly regulates fertilization an early embryogenesis, the regulatory mechanisms to gametes/zygote are still largely unknown. In this report, we studied the oviductal regulation of early embryonic development using Ovgp1 (a gene encoding an oviductal humoral factor, OVGP1)-knockout (KO) hamsters. The experimental results revealed the following: 1) Female Ovgp1-KO hamsters fail to produce any litters at all; 2) In the oviducts from KO animal, fertilized eggs are sometimes identified, but their morphology shows abnormal features; 3) The number of implantations in the KO females is evidently low; 4) Even if implantations occur, the embryos develop abnormally and eventually become embryonic lethal; and 5) Ovgp1-KO females transferred to wild-type females produce KO egg-derived litters, but the reverse experiment does not. These results suggest that OVGP1-mediated physiological events are crucial for early embryonic development in vivo. This animal model shows that the fate of the fertilized egg is not only genetically determined, but that the surrounding oviductal microenvironment plays a pivotal role in normal embryonic development. Summary statementDeficiency an oviductal humoral factor (OVGP1) caused female infertility in the golden hamsters. The presence or absence of OVGP1 has significant physiological effects on early embryonic development in vivo.

developmental biology↗

bioRxiv2022

A comprehensive analysis of the gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs

BackgroundLike its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota. ResultsStaphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and gut microbial composition. ConclusionsDysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota.

microbiology↗

bioRxiv2022

Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP

Site-2 proteases are a conserved family of intramembrane proteases that cleave transmembrane substrates to regulate signal transduction and maintain proteostasis. Here, we elucidated crystal structures of inhibitor-bound forms of bacterial site-2 proteases including E. coli RseP. Our observations are consistent with a rearrangement of the RseP domains surrounding the active center to expose the substrate-binding site where a conserved electrostatic linkage between the transmembrane and membrane-associated domains mediates the conformational changes, suggesting that RseP has a gating mechanism to regulate substrate entry. Mutational analysis also supports that the substrate transmembrane helix is unwound by strand addition to the intramembrane {beta} sheet and is clamped at the active center for efficient cleavage. Furthermore, this substrate accommodation mechanism appears to be common across distinct intramembrane proteases.

biochemistry↗

bioRxiv2021

North and East African mitochondrial genetic variation needs further characterization towards precision medicine

IntroductionMitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This work requires a comprehensive catalogue of commonly observed genetic variations in the mitochondrial DNAs for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied. ObjectivesTo address this shortcoming, we have created the most comprehensive quality-controlled North and East African mitochondrial dataset to date and use it for characterizing mitochondrial genetic variation in this region. MethodsWe compiled 11 published cohorts with novel data for mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n=2,504) and the Human Genome Diversity Project (n=828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination, as well as Nanopore long read sequencing for haplogroup validation of 18 samples. ResultsUsing a subset of high-coverage mitochondrial sequences, we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1. ConclusionOur findings demonstrate common hitherto unexplored variants in mitochondrial genomes of North and East Africa that lead to novel phylogenetic relationships between haplogroups present in these regions. These observations call for further in-depth population genetic studies in that region to enable the prospective use of mitochondrial genetic variation for precision medicine.

genetics↗