Biology subjects

Yi, S. V.

Publications and source records attributed to Yi, S. V..

9 recordsLinked to original sources

bioRxiv2026

The first reference genome assembly of the Chilean sea fig (Carpobrotus chilensis)

Carpobrotus chilensis (Chilean sea fig) is a coastal succulent of uncertain origin that has naturalized along the California coast, where it co-occurs and hybridizes with the invasive species, Carpobrotus edulis. Despite their ecological importance and widely supported hybridization, genomic resources for this genus remain scarce. Here, we present a draft genome assembly of C. chilensis generated from PacBio HiFi long reads. The assembled nuclear genome spans 981.7 Mb across 178 contigs. The contig N50 was 73.0 Mb, and BUSCO completeness was 96.3%. K-mer and SNP-based analyses indicate extremely low heterozygosity (3.4 x 10-), reduced genetic diversity in this population. The genome is highly repetitive, with 81.67% of the sequences composed of transposable elements, predominantly long terminal repeat (LTR) retrotransposons. Gene prediction identified 21,744 protein-coding genes, with BUSCO completeness of 95.8%. Comparative analysis with C. edulis identified 8,783 single-copy orthologous gene pairs, with a median synonymous substitution rate (dS) of 0.019, indicating low sequence divergence between the two species. This genome assembly provides a foundational resource for investigating the genomic basis of hybridization and invasion in Carpobrotus.

genomics↗

bioRxiv2026

Germline hypomethylation shapes dynamic CpG reservoirs in ape genomes

Telomere-to-telomere (T2T) genome assemblies resolve DNA methylation of complete ape genomes, including repetitive and satellite-rich compartments that were largely inaccessible in previous primate reference genomes. Here, integrating complete ape genome assemblies with long- and short-read germline and somatic DNA methylomes, we demonstrate dual roles of germline DNA methylation. While solidifying germline DNA methylation as a major driver of genome-wide long-term CpG erosion, we report an unexpected reservoir of hypomethylated CpGs that exist in previously inaccessible regions. Specifically, peri/centromeric satellites are markedly hypomethylated in sperm across great apes, despite their heterochromatic context and rapid sequence turnover. Moreover, we found their hypomethylation extends into adjacent non-satellite DNA at the boundaries of satellite-rich heterochromatic sequences and adjacent euchromatic sequences, forming centromeric hypomethylated extension domains, or CHEDs. CHEDs are enriched in recently duplicated genes, and CHED-associated genes show reproducible, enriched expression in the brain and testis. Extending our analyses to other structurally dynamic regions, including lineage-specific insertions, recent segmental duplications and structurally divergent regions, we show that these regions are also CpG-rich and relatively hypomethylated in sperm. Together, our results reveal a unique germline hypomethylation landscape in ape genomes in which structurally dynamic regions act not only as substrates of rapid genome evolution, but also as transient reservoirs of CpG-rich sequence contexts, promoting evolutionary innovations involving new genes and tissue-biased expression.

genomics↗

bioRxiv2025

Integrated Genomic and Methylome Profiling Reveals Promoter Repression and Age-Linked CpGs in the California Mussel

While most knowledge of animal DNA methylation comes from vertebrates, this epigenetic mark remains poorly understood in invertebrates, which comprise the majority of animal diversity. For instance, how promoter and gene body methylation contribute to gene regulation, and how methylation relates to aging, are still relatively unknown in most invertebrates. Focusing on the California mussel (Mytilus californianus), we paired whole-genome resequencing and whole-genome bisulfite sequencing from the same individuals and evaluated relationships among promoter methylation, gene body methylation, gene expression, and age. Using seven individuals spanning a range of body sizes from the Santa Barbara Channel, California, we found standing genetic variation levels similar to related species and a relatively small effective population size. CpG methylation was enriched in gene bodies, and gene body methylation was positively associated with expression. Promoter methylation was less frequent but showed a strong negative association with expression and remained the best predictor of repression after accounting for gene body methylation, aligning with patterns widely documented in vertebrates and adding to the limited evidence in invertebrates that promoter methylation can be regulatory. We identified thousands of age-associated differentially methylated loci with directional changes across age classes, providing candidate sites for epigenetic clocks that could enable assessment of biological age, health, and stress resilience in wild and cultured populations.

evolutionary biology↗

bioRxiv2025

Expanding canonical cortical cell type markers in the era of single-cell transcriptomics

Cell type markers have been instrumental to physiological and molecular investigation of the human brain and remain essential for annotating cell type clusters in single-cell expression data and for targeted validation studies. However, expression of canonical markers in the target cell type (which we termed as the expression fidelity) as well as expression in unrelated cell types (which we termed as the background expression) across cortical regions remains poorly characterized. Using nearly 500,000 high-quality single-nucleus profiles from 19 studies, we quantified marker fidelity, revealing substantial regional variability. We developed a statistical framework that aggregates annotated barcodes into pseudo-bulk profiles, applied rigorous performance metrics, and identified markers with improved fidelity, reduced background, and consistent expression across regions. This approach extended the canonical marker set for six major brain cell types and yielded superior subtype-specific markers. The resulting marker lists, and a user-friendly analysis interface, provide a valuable resource for cell type annotation and validation in neurological research.

neuroscience↗

bioRxiv2024

Whole-genome DNA methylomes of Tree shrew brains reveal conserved and divergent roles of DNA methylation on sex chromosome regulation

The tree shrew (Tupaia belangeri) is a promising emerging model organism in biomedical studies, notably due to their evolutionary proximity to primates. To enhance our understanding of how DNA methylation is implicated in regulation of gene expression and the X chromosome inactivation (XCI) in tree shrew brains, here we present their first genome-wide, single-base-resolution methylomes integrated with transcriptomes from prefrontal cortices. We discovered both divergent and conserved features of tree shrew DNA methylation compared to that of other mammals. DNA methylation levels of promoter and gene body regions are negatively correlated with gene expression, consistent with patterns in other mammalian brains studied. Comparing DNA methylation patterns of the female and male X chromosomes, we observed a clear and significant global reduction (hypomethylation) of DNA methylation across the entire X chromosome in females. Our data suggests that the female X hypomethylation does not directly contribute to the gene silencing of the inactivated X chromosome nor does it significantly drive sex-specific gene expression of tree shrews. However, we identified a putative regulatory region in the 5 end of the X inactive specific transcript (Xist) gene, a key gene for XCI, whose pattern of differential DNA methylation strongly relate to its differential expression between male and female tree shrews. We show that differential methylation of this region is conserved across different species. Moreover, we provide evidence suggesting that the observed difference between human and tree shrew X-linked promoter methylation is associated with the difference in genomic CpG contents. Our study offers novel information on genomic DNA methylation of tree shrews, as well as insights into the evolution of X chromosome regulation in mammals.

genomics↗

bioRxiv2022

Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

In white throated sparrows, two alternative morphs differing in plumage and behavior segregate with a large chromosomal rearrangement. As with sex chromosomes such as the mammalian Y, the rearranged version of chromosome two (ZAL2m) is in a near-constant state of heterozygosity, offering opportunities to investigate both degenerative and selective processes during the early evolutionary stages of supergenes. Here, we generated, synthesized, and analyzed extensive genome-scale data to better understand the forces shaping the evolution of the ZAL2m chromosome in this species. We found that features of ZAL2m are consistent with substantially reduced recombination and low levels of degeneration. We also found evidence that selective sweeps took place both on ZAL2m and its standard counterpart, ZAL2, after the rearrangement event. Signatures of positive selection were associated with allelic bias in gene expression, suggesting that antagonistic selection has operated on gene regulation. Finally, we discovered a region exhibiting two long-range haplotypes inside the rearrangement on ZAL2m. These two haplotypes appear to have been maintained by balancing selection, retaining genetic diversity within the supergene. Together, our analyses illuminate mechanisms contributing to the evolution of a young chromosomal polymorphism, revealing complex selective processes acting concurrently with genetic degeneration to drive the evolution of supergenes.

evolutionary biology↗

bioRxiv2021

Knockdown of Dnmt1 links Gene body DNA methylation to regulation of gene expression and maternal-zygotic transition in the wasp Nasonia

Gene body methylation (GBM) is an ancestral aspect of DNA methylation (Sarda, Zeng, Hunt, & Yi, 2012; Yi, 2012; Zemach, McDaniel, Silva, & Zilberman, 2010) whose role in development has been obscured by the more prominent roles of promoter and CpG island methylation. The wasp Nasonia has little promoter and CpG island methylation, yet retains strong GBM (Park et al., 2011; Wang et al., 2013; Werren et al., 2010), making it an excellent model for elucidating the role of GBM. Here we show that Nasonia DNA methyl transferase 1a (Nv-Dnmt1a) knockdown leads to failures in cellularization and gastrulation of the embryo. Both of these disrupted events are hallmarks of the maternal-zygotic transition (MZT) in insects. Analysis of the embryonic transcriptome and methylome revealed strong reduction of GBM and widespread disruption of gene expression during embryogenesis after Nv-Dnmt1a knockdown. There was a strong correlation between loss of GBM and reduced gene expression in thousands of methylated loci, while affected unmethylated genes tended to be upregulated. We propose that reduced GBM and subsequent lower expression levels of methylated genes was the direct effect of Nv-Dnmt1 knockdown, and that this disruption led to widespread downstream dysregulation of MZT, and manifesting in developmental failure at gastrulation. Significance StatementThe importance of gene-body methylation (GBM) in development is unclear, due to the difficulty in teasing apart the effects of cis-regulatory methylation from those of GBM in vertebrate model systems. Unlike vertebrate models, the methylation machinery in the jewel wasp Nasonia vitripennis appears to exclusively mediate GBM, thus simplifying interpretation of the role of GBM in development. Knockdown of DNMT1 (Nv-Dnmt1a) in Nasonia leads to embryonic lethality, which we show is caused by a failure of cellularization and gastrulation. Nv-Dnmt1a knockdown resulted in a global loss of GBM in the embryo, which was strongly correlated with a down-regulation of gene expression. We propose that GBM facilitated by Nv-Dnmt1a is required for proper zygotic genome activation in the wasp.

genomics↗

bioRxiv2020

Divergent DNA methylation signatures underlying X chromosome regulation in marsupials and eutherians

X chromosome inactivation (XCI) mediated by differential DNA methylation between sexes is well characterized in eutherian mammals. Although XCI is shared between eutherians and marsupials, the role of DNA methylation in marsupial XCI remains contested. Here we examine genome-wide signatures of DNA methylation from methylation maps across fives tissues from a male and female koala (Phascolarctos cinereus) and present the first whole genome, multi-tissue marsupial "methylome atlas." Using these novel data, we elucidate divergent versus common features of marsupial and eutherian DNA methylation. First, tissue-specific differential DNA methylation in marsupials primarily occurs in gene bodies. Second, females show significant global reduction (hypomethylation) of X chromosome DNA methylation compared to males. We show that this pattern is also observed in eutherians. Third, on average, promoter DNA methylation shows little difference between male and female koala X chromosomes, a pattern distinct from that of eutherians. Fourth, the sex-specific DNA methylation landscape upstream of Rsx, the primary lncRNA associated with marsupial XCI, is consistent with the epigenetic regulation of female-(and presumably inactive X chromosome-) specific expression. Finally, we utilize the prominent female X chromosome hypomethylation and classify 98 previously unplaced scaffolds as X-linked, contributing an additional 14.6 Mb (21.5 %) to genomic data annotated as the koala X chromosome. Our work demonstrates evolutionarily divergent pathways leading to functionally conserved patterns of XCI in two deep branches of mammals.

evolutionary biology↗

bioRxiv2020

Cell-type and cytosine context-specific evolution of DNA methylation in the human brain

Cell-type specific epigenetic modifications are critical for brain development and neuropsychiatric diseases. Here we elucidate evolutionary origins of neuron- and oligodendrocyte-specific DNA methylation in human prefrontal cortex, and demonstrate dynamic and distinctive changes of CG and CH methylation. We show that the human brain has experienced pronounced reduction of CG methylation during evolution, which significantly contributed to cell-type specific active regulatory regions. On the other hand, a substantial increase of CH methylation occurred during human brain evolution, associated with fine-tuning expression in development and neuronal subtypes. The majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and carries strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage and harbors additional genetic risk for schizophrenia, implicating epigenetic evolution of human cortex in increased vulnerability to neuropsychiatric diseases.

genomics↗