Biology subjects

To, T.-H.

Publications and source records attributed to To, T.-H..

5 recordsLinked to original sources

bioRxiv2025

Chromosome-level assembly of the octoploid cloudberry(Rubus chamaemorus)

We describe a chromosome-level genome assembly from an individual male plant of the cloudberry (Rubus chamaemorus). The haplotype-resolved assemblies contain one pseudo-haplotype spanning 1198 megabases and one pseudo-haplotype spanning 1161 megabases. Most of these two assemblies, 93.57% and 96.55% respectively, are each scaffolded into 28 pseudo-chromosomes. Both assemblies show high completeness, with the same BUSCO completeness score of 99.2%. Most BUSCO genes are duplicated in both pseudo-haplotypes, in line with the polyploid nature of the cloudberry genome. The assemblies contain 74,132 and 70,692 predicted protein-coding genes, respectively. Analysis of repetitive sequences classified [~]60% of each haplotype as repeats. Comparative synteny with red raspberry (Rubus idaeus) reveals a 4:1 chromosome correspondence, supporting an octoploid origin. Ks distributions and k-mer clustering indicate a fairly recent polyploidization involving one divergent ({beta}) and three closely related () subgenomes. Low coverage targeted sequencing data mapped to our assembly link the {beta}-subgenome to a relative of R. pedatus or R. lasiococcus, while the -subgenomes might derive from a putative auto-allohexaploid within the main Rubus clade. In conclusion, these results indicate that the cloudberry genome arose through multiple hybridization events, including recurrent allopolyploidy and possibly autopolyploidy. Significance statementCloudberry cultivation has lagged due to unclear origin and genome structure. We present a haplotype-resolved, chromosome-scale assembly that resolves four homologs per ancestral chromosome into 28 pseudo-chromosomes per haplotype and shows a 4:1 correspondence with red raspberry (Rubus idaeus). Genomic analyses indicate a recent polyploidization in which three closely related subgenomes likely derive from a putative hexaploid within the main Rubus clade, associated with R. arcticus (Arctic raspberry), whereas the fourth, more divergent subgenome is linked to relatives of R. pedatus (strawberryleaf raspberry) and R. lasiococcus (dwarf bramble). These results clarify cloudberrys formation and provide a foundation for trait discovery and accelerated breeding.

genomics↗

bioRxiv2025

Calcium starvation leads to strain-specific gene regulation of lipid and carotenoid production in Mucor Circinelloides

AO_SCPLOWBSTRACTC_SCPLOWFungi are pivotal in transitioning to a bio-based, circular economy due to their ability to transform organic material into valuable products such as organic acids, enzymes, and drugs. Mucor circinelloides is a model organism for studying lipogenesis and it particularly promising for its metabolic capabilities in producing oils like TAGs and carotenoids, influenced by environmental factors such as nutrient availability. Notably, strains VI04473 and FRR5020 have been identified for their potential in producing single-cell oils and carotenoids, respectively. Calcium starvation have previously been shown to have strain-specific effects, with VI04473 accumulating more lipids and FRR5020 producing more carotenoids. Here we used genome sequencing, comparative genomics, transcriptomics, and metabolite phenotyping to explore the genetic basis of lipid and carotenoid production under calcium starvation in these strains. We found extensive genomic rearrangements between these strains, as well as low conservation of gene regulatory responses to calcium depletion. This lack of conservation also applies to genes involved in lipid and carotenoid production, i.e. the lipidome. Several pathways show divergent regulation between strains, which explains the phenotypic divergence between VI04473 and FRR5020. The complex gene family evolution of several lipidome genes probably also affected specialization of these strains to calcium stress. Our study sheds light on the complexity of the evolution of metabolic networks in M. circinelloides. Understanding these genetic underpinnings can optimize the industrial use of M. circinelloides, enhancing lipid productivity and stress tolerance, and tailoring metabolic profiles for specific applications. This research advances our knowledge on complexity of fungal lipid metabolism and the role of calcium in regulating metabolic pathways.

genomics↗

bioRxiv2022

Identification of 121 variants of honey bee Vitellogenin protein sequences with structural differences at functional sites

Proteins are under selection to maintain central functions and to accommodate needs that arise in ever-changing environments. The positive selection and neutral drift that preserve functions result in a diversity of protein variants. The amount of diversity differs between proteins: multifunctional or disease-related proteins tend to have fewer variants than proteins involved in some aspects of immunity. Our work focuses on the extensively studied protein Vitellogenin (Vg), which in honey bees (Apis mellifera) is multifunctional and highly expressed and plays roles in immunity. Yet, almost nothing is known about the natural variation in the coding sequences of this protein or how amino acid-altering variants might impact structure-function relationships. Here, we map out allelic variation in honey bee Vg using biological samples from 15 countries. The successful barcoded amplicon Nanopore sequencing of 543 bees revealed 121 protein variants, indicating a high level of diversity in Vg. We find that the distribution of non-synonymous single nucleotide polymorphisms (nsSNPs) differs between protein regions with different functions; domains involved in DNA and protein-protein interactions contain fewer nsSNPs than the proteins lipid binding cavities. We outline how the central functions of the protein can be maintained in different variants and how the variation pattern may inform about selection from pathogens and nutrition.

biochemistry↗

bioRxiv2021

Genome-wide reconstruction of rediploidization following autopolyploidizationacross one hundred million years of salmonid evolution

The long-term evolutionary impacts of whole genome duplication (WGD) are strongly influenced by the ensuing rediploidization process. Following autopolyploidization, rediploidization involves a transition from tetraploid to diploid meiotic pairing, allowing duplicated genes (ohnologues) to diverge genetically and functionally. Our understanding of autopolyploid rediploidization has been informed by a WGD event ancestral to salmonid fishes, where large genomic regions are characterized by temporally delayed rediploidization, allowing lineage-specific ohnologue sequence divergence in the major salmonid clades. Here, we investigate the long-term outcomes of autopolyploid rediploidization at genome-wide resolution, exploiting a recent explosion of salmonid genome assemblies, including a new genome sequence for the huchen (Hucho hucho). We developed a genome alignment approach to capture duplicated regions across multiple species, allowing us to create 121,864 phylogenetic trees describing ohnologue divergence across salmonid evolution. Using molecular clock analysis, we show that 61% of the ancestral salmonid genome experienced an initial wave of rediploidization in the late Cretaceous (85-106 Mya). This was followed by a period of relative genomic stasis lasting 17-39 My, where much of the genome remained in a tetraploid state. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnologue divergence, scaling in complexity with the number of speciation events. Finally, using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. Overall, this study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.

genomics↗

bioRxiv2021

Cuban history of CRF19 recombinant subtype of HIV-1

CRF19 is a recombinant form of HIV-1 subtypes D, A1 and G, which was first sampled in Cuba in 1999, but was already present there in 1980s. CRF19 was reported almost uniquely in Cuba, where it accounts for ~25% of new HIV-positive patients and causes rapid progression to AIDS (~ 3 years). We analyzed a large data set comprising ~ 350 pol and env sequences sampled in Cuba over the last 15 years and ~ 350 from Los Alamos database. This data set contained both CRF19 (~ 315), and A1, D and G sequences. We performed and combined analyses for the three A1, G and D regions, using fast maximum likelihood approaches, including: (1) phylogeny reconstruction, (2) spatio-temporal analysis of the virus spread, and ancestral character reconstruction for (3) transmission mode and (4) drug resistance mutations (DRMs). This allowed us to acquire new insights on the CRF19 origin and transmission patterns. We showed that CRF19 recombined between 1966 and 1977, most likely in Cuban community stationed in Congo region. We further investigated CRF19 spread on the Cuban province level, and discovered that the epidemic started in 1970s, most probably in Villa Clara, that it was at first carried by heterosexual transmissions, and then quickly spread in the 1980s within the "men having sex with men" (MSM) community, with multiple transmissions back to heterosexuals. The analysis of the transmission patterns of common DRMs showed mostly acquired drug resistance rather than transmitted one. Our results show a very early introduction of CRF19 in Cuba, which could explain its local epidemiological success. Ignited by a major founder event, the epidemic then followed a similar pattern as other subtypes and CRFs in Cuba. The reason for the short time to AIDS remains to be understood and requires specific surveillance, in Cuba and elsewhere. Author summaryCRF19 is a recombinant form of HIV-1, which causes rapid progression to AIDS (~ 3 years versus 5 - 10 years for other subtypes and CRFs). CRF19 is reported almost uniquely in Cuba, where it is highly prevalent (~ 25%) among newly detected HIV-1 patients. In this study, we found that CRF19 most likely recombined around the 1970s in the Cuban community that was stationed in Democratic Republic of the Congo and Angola at that time. It was introduced very early into the Cuban province of Villa Clara, from where it had several introductions to La Habana in the 1980s and then further spread to other Cuban provinces. The CRF19 epidemic most probably started with heterosexual transmissions, followed in the 1980s by multiple introductions into "men having sex with men" (MSM) community, followed by multiple transmissions back to heterosexuals (often females). The early introduction of CRF19 into Cuba most likely explains its success, not observed in other parts of the world. However, importantly, its rapid progression to AIDS makes it crucial to survey CRF19 sub-epidemics not only in Cuba, but also in other parts of the world having regular exchanges with Cuba.

bioinformatics↗