Biology subjects

Osada, N.

Publications and source records attributed to Osada, N..

9 recordsLinked to original sources

bioRxiv2025

Population genomic scan of endogenous retrovirus insertions revealed cryptic drivers of selective sweep in wild house mouse genomes

Endogenous retroviruses (ERVs) represent a major source of structural variation in mammalian genomes, yet their diversity in wild populations remains poorly understood. Here, we conduct a comprehensive genome-wide survey of non-reference ERV insertions in wild house mice (Mus musculus) to characterize their distribution and evolutionary dynamics. Using a newly developed bioinformatics pipeline, we detected and annotated over 100,000 non-reference ERV insertions from short-read sequencing data across 163 wild mouse genomes. Our analyses revealed marked differences in ERV insertion patterns among subspecies and populations, including variation in genomic localization and population-specific polymorphisms. These heterogeneous patterns suggest distinct evolutionary histories and host-retrovirus interactions across populations. For instance, we describe the distribution of the ERV-derived Fv4 locus, which shows subspecies-restricted occurrence and confers resistance to murine leukemia viruses (MLVs). Several lines of evidence showed that the spread of Fv4 insertions in Korean population has been driven by adaptive introgression from neighboring populations. Our study provides the first large-scale population genomic scan of ERV diversity in wild house mice. By cataloguing extensive polymorphism in non-reference ERV insertions, our results highlight the role of ERVs as dynamic genomic elements that contribute to structural variation and adaptive evolution. Article SummaryEndogenous retroviruses (ERVs) are viral sequences embedded in animal genomes that can create structural genetic variation. In this study, we conducted a genome-wide survey of non-reference ERV insertions in 163 wild house mice using short-read sequencing data and a newly developed computational pipeline. We identified more than 100,000 polymorphic ERV insertions and found substantial differences among subspecies and geographic populations. One example, the ERV-derived Fv4 locus, illustrates how ERV variation can influence the genetic pattern of polymorphisms in the species. These results demonstrate that ERVs are dynamic genomic elements that contribute to population divergence and adaptive evolution.

evolutionary biology↗

bioRxiv2025

Whole-genome sequencing revealed local genetic differences and multi-layered genetic structure in brown bear (Ursus arctos) populations

A multi-layered genetic structure shaped by multiple demographic events across different time periods has been well documented in some species. However, evaluating this pattern remains challenging in many wide-ranging wildlife because genome-wide datasets with broad geographic coverage are still scarce. Brown bears are genetically differentiated among regional populations, but the genomic data are still limited and the demographic events remain incompletely understood. Here, we generated whole-genome resequencing data from brown bears in Asian local populations previously reported to show significant variation and combined these data with ancient samples for population genomic analyses. Our results support previously reported demographic events, such as the early divergence of Central Asian populations. Furthermore, we found genetic differences among Asian brown bear populations, suggesting that population-specific demographic histories occurring at different times have contributed to their unique genetic characteristics. In the Central and West Asian populations, divergence times estimated from autosomal genomes differed by hundreds of thousands of years from those inferred from mitochondrial DNA and Y-chromosomal DNA haplotypes, suggesting that gene flow continued after regional dispersal. In addition, the Y-chromosomal phylogeny and f4 statistics indicated genetic differentiation between the Kazakhstan and Tibetan populations, likely resulting from male-biased introgression into the Tibetan population. Finaly, the Hokkaido and Etorofu (Iturup) populations retained alleles derived from hybridization with polar bears, likely due to the limited impact of post-LGM population expansion. These findings indicate that the genetic variation among brown bear populations is shaped by multiple demographic events occurring at different times, resulting in a multi-layered genetic structure. Significance StatementMulti-layered genetic structure is well known in some species, but remains poorly understood in wild species due to limited genomic data. In this study, we newly sequenced nine brown bears in Asia which included bears that genome data in their area is unreported. By combining these with modern and ancient genomes, we conducted population genomic analyses to characterize local genetic variation and detect hybridization with related species such as the polar bear. We identified (1) substantial divergence time gaps in Central and West Asian populations between autosomal genomes and mitochondrial and Y-chromosomal haplotypes, (2) male-biased introgression into the Tibetan population, and (3) limited impact of recent expansion between island and Eurasian continental populations. These findings suggest that the genetic structure of the populations has been shaped by multiple demographic events at different times, resulting in a multi-layered genetic structure and providing new insights into how wildlife genetic diversity is shaped.

evolutionary biology↗

bioRxiv2023

Inference of Selective Force on House Mice Genomes during Secondary Contact in East Asia

The house mouse (Mus musculus), commensal to humans, has spread globally via human activities, leading to secondary contact between genetically divergent subspecies. This pattern of genetic admixture can provide insights into the selective forces at play in this well-studied model organism. Our analysis of 163 house mouse genomes, with a particular focus on East Asia, revealed substantial admixture between the subspecies castaneus and musculus, particularly in Japan and southern China. We revealed, despite the admixture, all Y chromosomes in the East Asian samples belonged to the musculus-type haplogroup, potentially explained by genomic conflict under sex ratio distortion due to varying copy numbers of ampliconic genes on sex chromosomes. We also investigated the influence of selection on the post-hybridization of the subspecies castaneus and musculus in Japan. Even though the genetic background of most Japanese samples closely resembles the subspecies musculus, certain genomic regions overrepresented the castaneus-like genetic components, particularly in immune-related genes. Furthermore, a large genomic block containing a vomeronasal/olfactory receptor gene cluster predominantly harbored castaneus-type haplotypes in the Japanese samples, highlighting the crucial role of olfaction-based recognition in shaping hybrid genomes.

evolutionary biology↗

bioRxiv2021

Whole-genome sequencing of Vero E6 (C1008) and comparative analysis of four Vero cell sublines

The Vero cell line is an immortalized cell line established from kidney epithelial cells of the African green monkey. A variety of sublines have been established from the original cell line, which display different characteristics. In this study, we determined the whole-genome sequence of Vero E6 (C1008) and performed comparative analysis among Vero JCRB 0111, Vero CCL-81, Vero 76 and Vero E6. Analysis of the copy number changes and loss of heterozygosity revealed that all sublines share a large deletion and loss of heterozygosity on chromosome 12, which harbors type I interferon and CDKN2 gene clusters. We identified a substantial number of genetic differences among the sublines including single nucleotide variants, indels, and copy number variations. The spectrum of single nucleotide variants indicated a close genetic relationship between Vero JCRB0111 and Vero CCL-81, and between Vero 76 and Vero E6, and a considerable genetic gap between the former two and the latter two lines. In contrast, we confirmed the pattern of genomic integration sites of simian endogenous retroviral sequences, which was consistent among the sublines. We identified subline-specific/enriched loss of function and missense variants, which potentially contribute to the differences in response to viral infection among the Vero sublines. In particular, we focused on Vero E6-specific/enriched variants and identified four genes (IL1RAP, TRIM25, RB1CC1, and ATG2A) that contained missense variants specific or enriched in Vero E6. In addition, we found that V739I variants of ACE2, which functions as the receptor for SARS-CoV-2, were heterozygous in Vero JCRB0111, Vero CCL-81, and Vero 76; however, Vero E6 contained the allele with isoleucine, resulting from the loss of one of the X chromosomes.

genomics↗

bioRxiv2021

Whole-genome sequencing analysis reveals the population history of Mus musculus in Madagascar

In Madagascar, the house mouse (Mus musculus) is thought to have colonized with human activities and is now one of the most abundant rodents on the island. In this study, we determined the whole-genome sequences of five Madagascar house mice captured from the wild. We examined the evolutionary history of the population by analyzing the mitochondrial and autosomal genomes. We confirmed that the mitochondrial genome lineages of Madagascar house mice formed a monophyletic clade placed at one of the most basal positions in the species. An analysis of autosomal genomic sequences indicates that the Madagascar house mice are genetically members of M. m. castaneus (CAS), but also contain genetic elements of M. m. domesticus (DOM) resulting from hybridization between subspecies. The signature of a strong population bottleneck 1000-3000 years ago was observed in both mitochondrial and autosomal genomic data. All samples showed strong genetic affinity to many CAS samples across a wide range of Indian Ocean coastal and island regions, with divergence time estimated around 4000 years ago. These findings support that the Madagascar house mice started to colonize the island with human agricultural activity, and experienced complex history for the establishment.

genetics↗

bioRxiv2021

Insights into Mus musculus subspecies population structure across Eurasia revealed by whole-genome sequence analysis

For more than 100 years, house mice (Mus musculus) have been used as a key animal model in biomedical research. House mice are genetically diverse, yet their genetic background at the global level has not been fully understood. Previous studies suggested that they originated in South Asia and diverged into three major subspecies almost simultaneously, approximately 350,000-500,000 years ago; however, they have spread across the world with the migration of modern humans in prehistoric and historic times ([~]10,000 years ago to present), and undergone secondary contact, which have complicated the genetic landscape of wild house mice. In this study, we sequenced the whole genomes of 98 wild house mice collected from Eurasia, particularly East Asia, Southeast Asia, and South Asia. We found that although wild house mice consist of three major genetic groups corresponding to the three major subspecies, individuals representing admixture between subspecies are much more ubiquitous than previously recognized. Furthermore, several samples showed an incongruent pattern of genealogies between mitochondrial and autosomal genomes. Using samples likely retaining the original genetic components of subspecies with least admixture, we estimated the pattern and timing of divergence among the subspecies. The results are important for understanding the genetic diversity of wild mice on a global level and the information will be particularly useful in future biomedical and evolutionary studies using laboratory mice established from these wild mice.

genomics↗

bioRxiv2020

Sex-biased migration and admixture in macaque species revealed by comparison between autosomal and X-chromosomal genomic sequences

The role of sex-specific demography in hybridization and admixture of genetically diverged species and populations is essential to understand the mechanisms forming the genomic diversity of sexually reproducing organisms. In order to infer how sex-linked genetic loci have been differentiated undergoing frequent hybridization and admixture, we examined 17 whole-genome sequences of seven species of the genus Macaca, which shows frequent inter-specific hybridization and predominantly female philopatry. We found that hybridization and admixture were prevalent within these species. For three cases of suggested hybrid origin of species/subspecies, M. arctoides, M. fascicularis ssp. aurea, and Chinese M. mulatta, we examined the level of admixture of X chromosomes, which is less affected by male-biased migration than that of autosomes. In one case, we were able to determine that M. cyclopis and M. fuscata was genetically closer to Chinese M. mulatta than to the Indian M. mulatta, and the admixture level of Chinese M. mulatta and M. fuscata/cyclopis was more pronounced on the X chromosome than on autosomes. Since the mitochondrial genomes of Chinese M. mulatta, M. cyclopis, and M. fuscata were found to cluster together, and the mitochondrial genome of Indian M. mulatta is more distantly related, the observed pattern of genetic differentiation on X-chromosomal loci is consistent with the nuclear swamping hypothesis, in which strong, continuous male-biased introgression from the ancestral Chinese M. mulatta population to a population related to M. fuscata and M. cyclopis generated incongruencies between the genealogies of the mitochondrial and autosomal genomes.

evolutionary biology↗

bioRxiv2020

Identification of characteristic genomic markers in human hepatoma Huh7 and Huh7.5.1-8 cell lines

The human hepatoma-derived Huh7 cell line and its derivatives (Huh7.5 and Huh7.5.1) have been widely used as a convenient experimental substitute for primary hepatocytes. In particular, these cell lines represent host cells suitable for propagating the hepatitis C virus (HCV) in vitro. The Huh7.5.1-8 cell line, a subline of Huh7.5.1, can propagate HCV more efficiently than its parental cells. To provide genomic information for cells quality control, we performed whole-genome sequencing of Huh7 and Huh7.5.1-8 and identified their characteristic genomic deletions, some of which are applicable to an in-house test for cell authentication. Among the genes related to HCV infection and replication, 53 genes were found to carry missense or loss-of-function mutations likely specific to the Huh7 and/or Huh7.5.1-8. Eight genes, including DDX58 (RIG-I), BAX, EP300, and SPP1 (osteopontin), contained mutations observed only in Huh7.5.1-8 or mutations with higher frequency in Huh7.5.1-8. These mutations might be relevant to phenotypic differences between the two cell lines and may also serve as genetic markers to distinguish Huh7.5.1-8 cells from the ancestral Huh7 cells.

genomics↗

bioRxiv2019

Exome sequences of toque macaques (Macaca sinica) of Sri Lanka reveal many amino acid changes

Macaques are one of the most widely used model organisms in biomedical research. Macaca mulatta and M. fascicularis are currently being used for toxicology, HIV, diabetes, neuroscience and psychiatric and psychological disorder researches. Many studies have been conducted on M. mulatta and M. fascicularis genomes for this purpose in order to understand the genomic properties of these species. Several M. fascicularis individuals from different geographical locations and also M. mulatta genomes have been sequenced and studied in depth for the purpose of understanding the phylogenetic and evolutionary relationships between various macaque populations. But still a gap in knowledge remains for other macaque populations such as the Sinica group. In this study for the very first time, we sequenced the exome of toque macaques (M. sinica), an endemic island population of Sri Lanka. Here we confirmed that M. sinica and M. thibetana cluster together and are closely related, also the three distinct phylogenetic groupings of fascicularis and sinica. We also found that M. sinica has less number of polymorphisms with respect to the reference genome M. mulatta signifying the smaller and restricted population size of this species.

evolutionary biology↗