Biology subjects

Yoneda, M.

Publications and source records attributed to Yoneda, M..

13 recordsLinked to original sources

bioRxiv2026

Oxidized phosphatidylinositol impairs lysosomal membrane repair to promote ferroptosis

Ferroptosis is a regulated form of cell death driven by iron-dependent and unrestrained lipid peroxidation, which generates phospholipid hydroperoxides that cause membrane rupture. Oxidized phospholipid species, including oxidized arachidonic acid-containing phosphatidylethanolamines (PE), are abundant during ferroptosis. However, previous studies have examined only a limited number of lipid species, and it remains unclear which oxidized phospholipids consistently arise across distinct cell types and ferroptosis-inducing conditions. Here, we comprehensively profiled oxidized phospholipids generated during ferroptosis across multiple cell lines and animal models. We identified PE 18:0_20:4;O3 and phosphatidylinositol (PI) 18:0_20:4;O3 as oxidized phospholipid species that are consistently detectable across all tested ferroptosis-inducing conditions. Furthermore, oxidized phosphatidylinositol impairs the phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway, a key mechanism for lysosomal membrane repair. These results indicate that the oxidized phospholipids identified here may serve as markers of ferroptosis while also acting as bioactive mediators that compromise lysosomal membrane homeostasis and repair.

cell biology↗

bioRxiv2026

Denisovan leg bones from Taiwan reveal large body size

Denisovans are an extinct archaic Homo group whose lineage diverged from the Neanderthal lineage approximately 550,000 years ago and were widely distributed across eastern Asia until [~]45,000 years ago1-7. Their morphological features are known directly from the existing cranio- dental and phalangeal remains1,2,8-12. However, the body size and postcranial morphology of the Denisovans remain largely unknown. We here report that hominin femoral and tibial fossils recovered from the Penghu Channel, Taiwan, are Denisovans in their proteomic profiles. Morphologically, these specimens are among the largest leg bones known in Pleistocene Homo. They exhibit generally archaic features, but also show some modern human-like morphology, including a strong femoral pilaster. Our findings demonstrate that the Denisovan population at the northern circle had larger body size than earlier Homo erectus as well as Late Pleistocene Homo sapiens in eastern Asia. This challenges the generally held expectation that Pleistocene Homo followed Bergmanns rule that anticipates latitudinal decline of body size, and suggests that the large Denisovan brain resulted from their large body size at least partly. The strong pilaster developed in the Penghu femur suggests some behavioral similarities between the Denisovans and the Upper Palaeolithic modern humans and/or gene flow from the latter to the former.

paleontology↗

bioRxiv2026

Habitat and feeding ecology of a Denisovan from Late Pleistocene Taiwan

Denisovans, originally identified from ancient genome from Denisova Cave in Altai, were a sister group to the Neanderthals and were once widely distributed across diverse terrains in the north and south of eastern Asia1-5. Genomic studies suggest that there were multiple events of interbreeding between modern humans (Homo sapiens) and Denisovans somewhere in Asia6. However, little is known about Denisovan living environments, diet, ecological niche, the timing of their disappearance, and the possible coexistence with modern humans in different regions. Here we report the radiocarbon age and stable isotopic signature of Penghu 3, a large Denisovan tibia from Penghu Channel, Taiwan7. The results showed that Penghu 3 dates to approximately 45,000 years ago, the time when modern humans were already widespread in southern parts of Asia. This Denisovan individual inhabited a C4-dominated ecosystem, open environments such as savannahs and floodplains, or a mixture of both, and consumed a high proportion of animal protein similar to some European Neanderthals8-10, with no clear evidence for the use of aquatic resources. These findings have implications for the behavioral flexibility, large body size7, and eventual disappearance of the Denisovans.

paleontology↗

bioRxiv2026

Leveraging archaeological specimens to investigate failed invasions: A case study on Okhotsk pigs, northern Japan

Invasive species pose a major threat to biodiversity, yet our understanding of failed invasions/translocations, instances where alien/introduced species fail to establish, remains limited. Investigating the factors behind failed invasions is critical for improving prevention and management strategies for modern biological invasions. Here, we propose a novel framework that utilizes archaeological archives to uncover evidence of failed invasions. We estimated the biological and ecological factors contributing to the failed invasion of pigs from later prehistory to recent times (299 cal BC to 1900 AD) on Rebun Island in far northern Japan by synthesizing the evidence obtained from stable isotopes, zooarchaeology, and historical documents. Despite the anthropogenic introductions of pigs into Rebun Island, pigs did not establish a feral population and disappeared after ca. 1200 AD. We identified reduced propagule pressure, abiotic resistance due to the cold climate, and decreased resources as the three key factors that contributed to the disappearance of pigs. Pigs are one of the most widespread invasive species globally, and this study represents a novel approach to studying failed invasions using archaeological data, which aligns with the framework of conservation paleobiology.

ecology↗

bioRxiv2026

Ancient Ryukyu Jomon contributed to past and current genetic structure of Japanese populations

Characterized by the earliest use of pottery, the Jomon culture was a unique Neolithic culture that spread throughout the Japanese Archipelago. Previous archaeological evidence suggests that Jomon hunter-gatherers colonized the southernmost islands, the Ryukyu Archipelago, by approximately 7,000 years before present (YBP). However, genetic characteristics of the Ryukyu Jomon population and its contribution to the modern population have not been elucidated yet. In this study, we newly sequenced 273 modern and 25 ancient (6,700-900 YBP) whole genomes collected across the Ryukyu Archipelago. Our analysis demonstrated a genetic differentiation between the Hondo (Japanese mainland) and Ryukyu Jomon, dating back to [~]6,900 YBP. After the divergence from the Hondo Jomon, the Ryukyu Jomon experienced severe bottlenecks, with an effective population size of [~]2,000. Admixture between the Ryukyu Jomon and migrants from the historic Hondo population occurred [~]1,000 YBP, which corresponds to the widespread adoption of iron tools and agriculture in the Central Ryukyus. Different demographic histories between modern Hondo and Ryukyu populations resulted in different rates of Jomon ancestry in these populations. By providing a new perspective on the peopling of the Ryukyu Archipelago, this study significantly enhances our understanding of cultural transitions in the region.

evolutionary biology↗

bioRxiv2025

High-Coverage Jomon Genomes Provide Insights into Population Structure and Genetic Traits of Ancient Japanese Hunter-Gatherers

We analyzed eight high-coverage Jomon genomes spanning 9,000-2,800 years ago across the Japanese archipelago. Population genomic analyses revealed substantial genetic homogeneity across time and space reflecting post-glacial isolation, yet temporal stratification emerged: Initial Jomon (Iyai) individuals formed the earliest branch with weaker affinities to present-day Japanese. Using genomes from Todoroki and Chidorikubo sites, we estimated Jomon ancestry in mainland Japanese at [~]20%, substantially higher than previous estimates ([~]13%). Polygenic score analyses, based on the direct analysis of Jomon genomes, provided the genetic evidence for their phenotypic predispositions, including elevated BMI and metabolic trait scores, reduced immune-related scores, and larger cardiac dimensions, patterns consistent with hunter-gatherer adaptations. These ancestral genetic influences, including elevated risks for obesity and dyslipidemia, persist in present-day Japanese. Our findings demonstrate that Jomon populations maintained genetic continuity despite ecological diversity, while their greater-than-expected contribution to present-day Japanese reshapes population history models and reveals how ancient adaptations continue influencing contemporary disease susceptibility.

genomics↗

bioRxiv2025

Carbon and nitrogen stable isotopic profiling of chimpanzees and other primate hairs in Kalinzu Forest Reserve, Uganda

Stable isotope analysis is a widely used tool in primate ecology for investigating diet and environment, with numerous studies focusing on chimpanzees. However, few studies have explored the dietary niche of chimpanzees in comparison to other primates or examined intra-individual dietary variability. This limitation hinders the understanding of the comparability of isotopic data with the wealth of behavioral observational data in primate ecology. In this study, we report the carbon and nitrogen stable isotope ratios of hairs from wild chimpanzees and four other primate species in the Kalinzu Forest Reserve, Uganda. Bulk analysis revealed that both plant foods and chimpanzees in Kalinzu exhibited lower carbon isotope ratios than expected for the regions rainfall. Additionally, preliminary compound-specific nitrogen isotope analysis of amino acids was conducted, revealing that chimpanzees in Kalinzu have a lower degree of faunivory than the sympatric Cercopithecus primates. Furthermore, ultra-fine sectioning of a hair sample was conducted to investigate dietary variation over daily to weekly timescales. In one adult male chimpanzee, carbon and nitrogen isotope ratios fluctuated by more than 1{per thousand} within approximately 10 days. These findings highlight the importance of recognizing uncontrolled ecological variability and hidden intra-individual dietary changes when interpreting stable isotope data in relation to behavior and environmental traits.

ecology↗

bioRxiv2024

Endemic demographics of the Jomon people estimated based on complete mitogenomes reveal their regional diversity

The Jomon culture that spread across Japanese archipelago began about 16,000 years ago and lasted for over 10,000 years. The genetic diversity of the Jomon people, prehistoric hunter-gatherers bearing the Jomon culture, is of great interest in understanding prehistoric East Eurasians. Until now, their demographic history has been estimated using archaeological sites and present-day genomes, but detailed studies using Jomon genomes have been insufficient. To investigate the Jomon demography, we determined the complete mitochondrial genome (mitogenome) sequences from 13 Jomon individuals and conducted population genetic analysis on 40 Jomon genomes including previously published data. Our results revealed an effective population size increase during the Incipient - Initial phase of the Jomon period, which had not been observed in analysis of mitogenome sequences from present-day Japanese populations. This endemic demographic pattern is pronounced in the eastern part of the archipelago, under the assumption of no gene flow between the Eastern and Western Jomon.

genomics↗

bioRxiv2024

Cold adaptation in Upper Paleolithic hunter-gatherers of eastern Eurasia

Previous genomic studies understanding the dispersal of Homo sapiens have suggested that present-day East Eurasians and Native Americans can trace their ancestry to migrations from Southeast Asia. However, ineluctable adaptations during the Last Glacial Maximum (LGM) remain unclear. By analyzing 42 genomes of up to 30-fold coverage from prehistoric hunter-gatherers, Jomon, we reveal their descent from Upper Paleolithic (UP) foragers who migrated to and isolated in the Japanese archipelago during Late Pleistocene. We provide compelling evidence suggesting that these UP people underwent positive selection for cold environments, aiding their survival through the LGM facilitated by non-shivering thermogenesis and detecting it polygenically across multiple loci in the Jomon lineage. Our study pioneers the close estimation of the physiological adaptation of ancient humans by the paleogenomic approach.

evolutionary biology↗

bioRxiv2023

Palaeoproteomic investigation of an ancient human skeleton with abnormal deposition of dental calculus

Detailed investigation of extremely severe pathological conditions in ancient human skeletons is important as it could shed light on the breadth of potential interactions between humans and disease etiologies in the past. Here, we applied palaeoproteomics to investigate an ancient human skeletal individual with severe oral pathology, focusing our research on bacterial pathogenic factors and host defense response. This female skeleton, from the Okhotsk period (i.e., 5th-13th century) of Northern Japan, poses relevant amounts of abnormal dental calculus deposition and exhibits oral dysfunction due to severe periodontal disease. A shotgun mass-spectrometry analysis identified 81 human proteins and 15 bacterial proteins from the calculus of the subject. We identified two pathogenic or bioinvasive proteins originating from two of the three "red complex" bacteria, the core species associated with severe periodontal disease in modern humans, as well as two additional bioinvasive proteins of periodontal-associated bacteria. Moreover, we discovered defense response system-associated human proteins, although their proportion was mostly similar to those reported in ancient and modern human individuals with lower calculus deposition. These results suggest that the bacterial etiology was similar and the host defense response was not necessarily more intense in ancient individuals with significant amounts of abnormal dental calculus deposition.

evolutionary biology↗

bioRxiv2023

Collagen of ancient bones gives an indication of endogenous DNA preservation based on the next generation sequencing technology

Ancient genome analysis has become an indispensable tool in studies of human population history and evolution after the breakthrough of whole genome sequencing technology. Meanwhile, the problem has been not resolved that ancient genome cannot be analyzed without crushing non-small pieces of precious specimens; in spite of that, in many cases, there is no DNA remaining sufficiently in the piece of samples for obtaining the whole genome sequences. In previous studies, therefore, a couple of indicators (e.g., racemization ratios) have been proposed to estimate the endogenous DNA in ancient samples. However, these studies have used polymerase chain reaction (PCR) to test whether endogenous DNA is remaining, which has been inadequate because the success or failure of PCR amplification does not necessarily reflect DNA remaining. To assess the amount of endogenous DNA, we use the ratios of reads generated by the next-generation sequencer (NGS) mapped to the human reference genome sequence. We investigate 40 Jomon remains and find a significant association between the collagen residual ratios (CRRs) in rib bones and the mapping ratios (MRs). Because the weight of bone required to measure collagen residual is much less than that required to obtain DNA needed for NGS analysis, which is always necessary for dating, the collagen in ribs can be a good indicator for successful ancient genome analyses.

genomics↗

bioRxiv2019

Epigenetic Effects of Exposure to Insecticide on Early Differentiation of Mouse Embryonic Stem Cells

Increasing evidence indicates that insecticides induce various diseases via DNA methylation. DNA methylation plays an important role during cell differentiation and exhibits its greatest vulnerability to environmental factors during embryogenesis. Therefore, it is important to evaluate the effects on DNA methylation at the early stage of cell differentiation to understand developmental toxicity. However, DNA methylation induced by insecticides and the associated effects on cell differentiation are unclear. In this research, we introduced a high-content approach utilizing mouse embryonic stem cells harboring enhanced green fluorescent protein fused with methyl CpG-binding protein to evaluate global DNA methylation induced by various insecticides. DNA methylation was assessed in 22 genes after pesticide exposure to investigate the relationships with biological processes such as cell cycle, cell apoptosis, and cell differentiation. Exposure to acetamiprid, imidacloprid, carbaryl, and o,p'-DDT increased the granular intensity, indicating their global DNA-methylating effects. Exposure to imidacloprid decreased DNA methylation in genes such as Cdkn2a, Dapk1, Cdh1, Mlh1, Timp3, and Rarb, indicating the potential influence of the DNA methylation pattern on cell differentiation. We developed a promising approach for evaluating global DNA methylation, and our findings suggested that imidacloprid might exhibit developmental effects through DNA methylation pattern.

pharmacology and toxicology↗

bioRxiv2019

Jomon genome sheds light on East Asian population history

Anatomical modern humans reached East Asia by >40,000 years ago (kya). However, key questions still remain elusive with regard to the route(s) and the number of wave(s) in the dispersal into East Eurasia. Ancient genomes at the edge of East Eurasia may shed light on the detail picture of peopling to East Eurasia. Here, we analyze the whole-genome sequence of a 2.5 kya individual (IK002) characterized with a typical Jomon culture that started in the Japanese archipelago >16 kya. The phylogenetic analyses support multiple waves of migration, with IK002 forming a lineage basal to the rest of the ancient/present-day East Eurasians examined, likely to represent some of the earliest-wave migrants who went north toward East Asia from Southeast Asia. Furthermore, IK002 has the extra genetic affinity with the indigenous Taiwan aborigines, which may support a coastal route of the Jomon-ancestry migration from Southeast Asia to the Japanese archipelago. This study highlight the power of ancient genomics with the isolated population to provide new insights into complex history in East Eurasia.

genomics↗