Biology subjects

Oota, H.

Publications and source records attributed to Oota, H..

11 recordsLinked to original sources

bioRxiv2026

An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population

Ancestry-related genomic variation may contribute to phenotypic diversity. However, its cellular consequences remain difficult to evaluate. To address this, we developed a human induced pluripotent stem cell (hiPSC)-based framework for investigating such phenotypes. We used the Japanese population as a model of Jomon-related and continental East Asian ancestry admixture. Jomon ancestry, estimated using the Jomon allele score (JAS), was associated with clinical measures, including renal-related traits and serum triglycerides in 34,152 Tohoku Medical Megabank participants. Peripheral blood mononuclear cell transcriptomics of donors from the upper and lower extremes of the JAS distribution (n = 10) suggested group-level differences in immune-related gene expression. To test whether the serum triglyceride association coincided with hepatic cellular phenotypes, we differentiated hiPSCs from these donors into hepatocyte-like cells. Neither intracellular triglycerides nor lipid-related gene expression differed between groups. These findings highlight the value of a genetically characterized hiPSC-based framework for investigating ancestry-associated phenotypes across cellular contexts.

genomics↗

bioRxiv2026

Female-biased continental farmer ancestry contribution to the modern Japanese genome

Modern mainland Japanese formed through admixture between the Jomon hunter- gatherers and continental farmers who arrived probably in northern Kyushu around 3,000 years ago (the dual-structure model). Although Jomon ancestry accounts for only [~]10-20% of the autosomes, the Jomon-associated Y-chromosome haplogroup D1a2a reaches [~]35% in present-day Japanese males--an "admixture paradox" often attributed to a larger contribution by Jomon males, though this has never been tested genome-wide. To test whether this admixture was sex-biased, here we compared the X chromosome with the autosomes. Using Jomon-derived variants as local-ancestry markers, we separated the modern Japanese genome into Jomon-related and continental East Asian-related ancestry components and computed the Keinan-type autosome-to-X drift ratio (Q, neutral expectation 0.75) for each. The continental East Asian-related component gave a significantly higher Q than the Jomon-related component ({Delta} = Qfarming - QHG = 0.10, P = 9.1 x 10 {square}3). Relative to the neutral value of 0.75, the Jomon-related component was indistinguishable from neutrality (Q = 0.78, P = 0.34), whereas the continental East Asian-related component was significantly higher (Q = 0.88, P = 4.2 x 10{square} {square}). Under a single-pulse founder model, this pattern implies a continental farmer contribution that was significantly more female-biased than the Jomon hunter-gatherer contribution, with no detectable departure from sex balance in the latter. Monte Carlo simulations showed that the inferred sex ratios account for much of the observed D1a2a frequency, although the remaining discrepancy indicates that additional demographic processes may have contributed. The ancestry asymmetry in the modern Japanese genome was thus driven primarily by a female-biased contribution of continental farming migrants, rather than by the male-biased Jomon contribution conventionally invoked to explain the admixture paradox.

evolutionary biology↗

bioRxiv2026

Functional divergence of DSCAM family in vertebrates through domain-specific evolutionary pressures

The Down syndrome cell adhesion molecule (DSCAM) family, conserved across metazoans, plays key roles in neural development by mediating cell-cell recognition. Invertebrate Dscam evolved extensive molecular diversity through isoform diversification, whereas the vertebrate paralogs DSCAM and DSCAML1 followed a distinct evolutionary trajectory. However, how these vertebrate paralogs evolved after duplication, particularly with respect to functional divergence, remains poorly understood. Here, we investigated the evolutionary history and post-duplication divergence of these paralogs using phylogenetic, molecular evolutionary, sequence comparison, and transcriptomic analyses. Our phylogenetic analyses suggest an ancestral gene duplication predating the split between gnathostomes and cyclostomes. We found distinct patterns of selective constraint between the paralogs, particularly in the intracellular domain. In tetrapods, the intracellular domain of DSCAM showed strengthened purifying selection, whereas no comparable reinforcement was evident for DSCAML1, despite strong constraint in mammals. We also found distinct patterns of lineage- and site-specific positive selection between DSCAM and DSCAML1. Consistent with these evolutionary differences, comparative analysis of the intracellular domains revealed distinct repertoires of short linear motifs (SLiMs) predicted to mediate protein-protein interactions. Reanalysis of published transcriptomic data further suggested distinct downstream responses elicited by the intracellular domains of DSCAM and DSCAML1. Together, these findings suggest that post-duplication functional divergence of vertebrate DSCAM paralogs may have contributed to the evolution of molecular mechanisms underlying vertebrate neural development and circuit formation.

evolutionary biology↗

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

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

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↗

bioRxiv2019

Exploring deep-time relationships between cultural and genetic evolution in Northeast Asia

Culture evolves in ways that are analogous to, but distinct from, genomes. Previous studies examined similarities between cultural variation and genetic variation (population history) at small scales within language families, but few studies empirically investigated such parallels across language families using diverse cultural data. We report an analysis comparing culture and genomes from in and around Northeast Asia spanning 11 language families. We extract and summarize the variation in language (grammar, phonology, lexicon), music (song structure, performance style), and genomes (genome-wide SNPs) and test for correlations. We find that grammatical structure correlates with population history. Recent contact and shared descent fail to explain the signal, suggesting relationships that arose before the formation of current families. Our results suggest that grammar might be a cultural indicator of population history, while also demonstrating differences among cultural and genetic relationships that highlight the complex nature of human history.

evolutionary biology↗

bioRxiv2018

A new targeted capture method using bacterial artificial chromosome (BAC) libraries as baits for sequencing relatively large genes

To analyze a specific genome region using next-generation sequencing technologies, the enrichment of DNA libraries with targeted capture methods has been standardized. For enrichment of mitochondrial genome, a previous study developed an original targeted capture method that use baits constructed from long-range polymerase chain reaction (PCR) amplicons, common laboratory reagents, and equipment. In this study, a new targeted capture method is presented, that of bacterial artificial chromosome (BAC) double capture (BDC), modifying the previous method, but using BAC libraries as baits for sequencing a relatively large gene. We applied the BDC approach for the 214 kb autosomal region, ring finger protein 213, which is the susceptibility gene of moyamoya disease (MMD). To evaluate the reliability of BDC, cost and data quality were compared with those of a commercial kit. While the ratio of duplicate reads was higher, the cost was less than that of the commercial kit. The data quality was sufficiently the same as that of the kit. Thus, BDC can be an easy, low-cost, and useful method for analyzing individual genome region with substantial length.

genomics↗

bioRxiv2017

Medaka population genome structure and demographic history unveiled via Genotyping-by-Sequencing

Medaka is a model organism in medicine, genetics, developmental biology and population genetics. Lab stocks composed of more than 100 local wild populations are available for research in these fields. Thus, medaka represents a potentially excellent bioresource for screening disease-risk- and adaptation-related genes in genome-wide association studies. Although the genetic population structure should be known before performing such an analysis, a comprehensive study on the genome-wide diversity of wild medaka populations has not been performed. Here, we performed genotyping-by-sequencing (GBS) for 81 and 12 medakas captured from a bioresource and the wild, respectively. Based on the GBS data, we evaluated the genetic population structure and estimated the demographic parameters using an approximate Bayesian computation (ABC) framework. The autosomal data confirmed that there were substantial differences between local populations and supported our previously proposed hypothesis on medaka dispersal based on mitochondrial genome (mtDNA) data. A new finding was that a local group that was thought to be a hybrid between the northern and the southern Japanese groups was actually a sister group of the northern Japanese group. Thus, this paper presents the first population-genomic study of medaka and reveals its population structure and history based on autosomal diversity.

evolutionary biology↗

bioRxiv2017

Analysis of ancient human mitochondrial DNA from Verteba Cave, Ukraine: insights into the origins and expansions of the Late Neolithic-Chalcolithic Cututeni-Tripolye Culture

BackgroundThe Eneolithic (~ 5,500 yrBP) site of Verteba Cave in Western Ukraine contains the largest collection of human skeletal remains associated with the archaeological Cucuteni-Tripolye Culture. Their subsistence economy is based largely on agro-pastoralism and had some of the largest and most dense settlement sites during the Middle Neolithic in all of Europe. To help understand the evolutionary history of the Tripolye people, we performed mtDNA analyses on ancient human remains excavated from several chambers within the cave.\n\nResultsBurials at Verteba Cave are largely commingled and secondary in nature. A total of 68 individual bone specimens were analyzed. Most of these specimens were found in association with well-defined Tripolye artifacts. We determined 28 mtDNA D-Loop (368 bp) sequences and defined 8 sequence types, belonging to haplogroups H, HV, W, K, and T. These results do not suggest continuity with local pre-Eneolithic peoples, but rather complete population replacement. We constructed maximum parsimonious networks from the data and generated population genetic statistics. Nucleotide diversity ({pi}) is low among all sequence types and our network analysis indicates highly similar mtDNA sequence types for samples in chamber G3. Using different sample sizes due to the uncertainly in number of individuals (11, 28, or 15), we found Tajimas D statistic to vary. When all sequence types are included (11 or 28), we do not find a trend for demographic expansion (negative but not significantly different from zero); however, when only samples from Site 7 (peak occupation) are included, we find a significantly negative value, indicative of demographic expansion.\n\nConclusionsOur results suggest individuals buried at Verteba Cave had overall low mtDNA diversity, most likely due to increased conflict among sedentary farmers and nomadic pastoralists to the East and North. Early Farmers tend to show demographic expansion. We find different signatures of demographic expansion for the Tripolye people that may be caused by existing population structure or the spatiotemporal nature of ancient data. Regardless, peoples of the Tripolye Culture are more closely related to early European farmers and lack genetic continuity with Mesolithic hunter-gatherers or pre-Eneolithic groups in Ukraine.

evolutionary biology↗