Biology subjects

Gojobori, T.

Publications and source records attributed to Gojobori, T..

17 recordsLinked to original sources

bioRxiv2025

Widespread and Abundant CRISPR-Cas Systems in the Deep Ocean

CRISPR-Cas systems have revolutionized modern biology. Most CRISPR-Cas systems in use for biotechnological applications derive from cultivated bacteria, but evidence suggests that environmental microbiomes harbor a large untapped diversity of these systems. Yet, our understanding of which environmental and biological factors drive the prevalence of CRISPR-Cas systems in the oceans remains limited. A search for CRISPR-Cas systems was conducted among 176 globally-distributed marine microbial metagenomes from the Malaspina expedition, which sampled both free-living and particle-attached microbiomes with emphasis on the deep ocean. We show that CRISPR-Cas systems are proportionally more abundant among microbiomes from the deep ocean than in the photic layers and among free-living microbes compared to those attached to particles, reflecting the higher concentrations of archaea and their viruses in these habitats. We identified 1,146 CRISPR-cas loci, some of which displayed unique loci architectures. From these loci, a total of 48 Cas9 proteins were identified, many of which are potentially novel. These discoveries expand the scope of CRISPR-Cas diversity and point at the deep-sea as a rich reservoir of these resources, which helps guide future bioprospecting efforts.

microbiology↗

bioRxiv2024

Chromosome-scale pearl millet genomes reveal a CARLACTONOIC ACID METHYL TRANSFERASE as key determinant of strigolactone pattern and Striga susceptibility

The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released strigolactones (SLs) for seed germination. Herein, we identified four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10), but absent in the resistant 29Aw (Aw). We generated chromosome-scale genome assemblies including four gapless chromosomes for each line. We found the Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYL TRANSFERASE1 (CLAMT1) genes. Upon transient expression, P10CLAMT1b produced methyl carlactonoate (MeCLA), an intermediate in SL biosynthesis. Feeding Aw with MeCLA resulted in the production of two P10-specific SLs. Screening a diverse pearl millet panel confirmed the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

plant biology↗

bioRxiv2023

Genetic characterization and dissemination of Staphylococcus aureus and Staphylococci genus: food and health perspective

Hospitals and communities are significant hubs for antibiotic-resistant staphylococcal infections, but recently there have been spread of the Staphylococci to other settings including farms and food chains. This study aimed to compare the methicillin-resistant Staphylococcus aureus (MRSA) isolates from humans and food to understand the genetic characteristics and similarities between the circulating clones across both groups. A total of 250 samples of meat (camel, beef, chicken, fish, and lamb) were collected from different retailers in Riyadh, Saudi Arabia. Culture, and Genomics analysis of the isolates yielded 53 S.aureus out of which (42/53; 79%) were methicillin-sensitive S.aureus (MSSA) and (11/53; 21%) were MRSA in addition to to other Staphylococci. 80 clinically confirmed MRSA isolates were obtained from patients in the same city. The most common S. aureus clone in patients and retail meat belonged to clonal complex (CC5). In meat, ST6 and ST97 were the most common clones found in (6/11; 54.5%) of MRSA isolates, and ST1153 (9/42; 21.42%), ST672 (7/42; 16.66%) of MSSA isolates. The majority of MRSA isolates in meat carried SCCmec type V, which was observed in (6/11; 54.54%) of isolates. While in patients, ST5 and ST6 were the predominant clones found in (37/80; 46%) of MRSA isolates. The most prevalent SCCmec types in MRSA isolates from patients were SCCmec type IVa, which was observed in (39/80; 48.7%) of isolates. While there was no MRSA found in beef, camel meat had the highest prevalence of MRSA ST6-t2450 contamination. The other two clones, CC97 and CC361, were the second-most prevalent clones in meat and were relatively common among patients. Novel S. aureus lineages were sequenced and characterized for the first time ST8109 from meat and ST8110 and ST8111 from patients. A structured One Health approach on S. aureus considering its dissemination, genetic characterization, antibiotic resistance, and overall impact on food intended for human consumption and its effect on human health is advised.

microbiology↗

bioRxiv2023

Marine picoplankton metagenomes from eleven vertical profiles obtained by the Malaspina Expedition in the tropical and subtropical oceans

The Ocean microbiome has a crucial role on Earths biogeochemical cycles, but also represents a tremendous potential for biological applications as part of the bluebiotechnology. During the last decade, global cruises such as Tara Oceans or the Malaspina Expedition have expanded our knowledge on the diversity and genetic repertoire of marine microbes. Nevertheless, there is still a gap of knowledge on broad scale patterns between photic and bathypelagic dark ocean microbes derived from the lack of detailed vertical profiles covering contrasting oceans depth regions. Here we present a dataset of 76 microbial metagenomes of the picoplankton size fraction (0.2-3.0 m) collected in 11 stations along the Malaspina Expedition circumnavigation that cover vertical profiles sampling at 7 depths, from the surface to the 4000 m deep (or the sea floor in shallower waters). This Malaspina Microbial Vertical Profiles metagenomes (MProfile) dataset produced 1.66 Tbp of raw DNA sequences that assembled into a total 25.3 Gbp. After gene prediction and annotation, we built a 46.3 million non-redundant gene compendium with their corresponding annotations (M-GeneDB-VP), clustered at 95% sequence similarity. This dataset will be a valuable resource for exploring the functional and taxonomic connectivity between the photic and bathypelagic tropical and subtropical ocean at a global scale, while increasing our general knowledge on the Ocean microbiome.

microbiology↗

bioRxiv2022

Abundant deep ocean heterotrophic bacteria are culturable

Traditional culture techniques usually retrieve only a small fraction of the environmental marine microbial diversity, which mainly belong to the so-called rare biosphere. However, this paradigm has not been fully tested at a broad scale, especially in the deep ocean. Here, we examined the fraction of heterotrophic bacterial communities in photic and deep ocean layers that could be recovered by culture-dependent techniques at a large scale. We compared 16S rRNA gene sequences from a collection of 2003 cultured isolates of heterotrophic marine bacteria with global 16S rRNA metabarcoding datasets (16S TAGs) covering surface, mesopelagic and bathypelagic ocean samples that included 16 of the 22 samples used for isolation. These global datasets represent 60,322 unique 16S amplicon sequence variants (ASVs). Our results reveal a significantly higher proportion of isolates identical to ASVs in deeper ocean layers reaching up to a 28% of the 16S TAGs of the bathypelagic microbial communities, which included the isolation of 3 of the top 10 most abundant 16S ASVs in the global bathypelagic ocean, related to the genera Sulfitobacter, Halomonas and Erythrobacter. These cultured isolates contributed differently to the prokaryotic communities across different plankton size fractions, recruiting between 38% in the free-living size fraction (0.2-0.8 m) and up to 45% in the largest plankton size fraction (20-200 m) in the bathypelagic ocean. Our findings support the hypothesis that sinking particles in the bathypelagic realm act as resource-rich habitats, suitable for the growth of heterotrophic bacteria with a copiotroph lifestyle that can be cultured, and that these cultivable bacteria can also thrive as free-living bacteria.

ecology↗

bioRxiv2021

Rapid Evolution of SARS-CoV-2 Challenges Human Defenses

Evolutionary ecology theory provides an avenue to anticipate the future behavior of SARS-CoV-2. Here we quantify the accelerating evolution of SARS-CoV-2 by tracking the SARS-CoV-2 mutation globally, with a focus on the Receptor Binding Domain (RBD) of the spike protein believed to determine infectivity. We estimate that 384 million people were infected by March 1st, 2021, producing up to 1021 copies of the virus, with one new RBD variant appearing for every 600,000 human infections, resulting in approximately three new effective RBD variants produced daily. Doubling the number of RBD variants every 71.67 days followed by selection of the most infective variants challenges our defenses and calls for a shift to anticipatory, rather than reactive tactics. One-Sentence SummaryAccelerating evolution of SARS-CoV-2 demands formulating universal vaccines and treatments based on big-data simulations of possible new variants.

evolutionary biology↗

bioRxiv2021

DeepSVP: Integration of genotype and phenotype for structural variant prioritization using deep learning

MotivationStructural genomic variants account for much of human variability and are involved in several diseases. Structural variants are complex and may affect coding regions of multiple genes, or affect the functions of genomic regions in different ways from single nucleotide variants. Interpreting the phenotypic consequences of structural variants relies on information about gene functions, haploinsufficiency or triplosensitivity, and other genomic features. Phenotype-based methods to identifying variants that are involved in genetic diseases combine molecular features with prior knowledge about the phenotypic consequences of altering gene functions. While phenotype-based methods have been applied successfully to single nucleotide variants as well as short insertions and deletions, the complexity of structural variants makes it more challenging to link them to phenotypes. Furthermore, structural variants can affect a large number of coding regions, and phenotype information may not be available for all of them. ResultsWe developed DeepSVP, a computational method to prioritize structural variants involved in genetic diseases by combining genomic and gene functions information. We incorporate phenotypes linked to genes, functions of gene products, gene expression in individual celltypes, and anatomical sites of expression, and systematically relate them to their phenotypic consequences through ontologies and machine learning. DeepSVP significantly improves the success rate of finding causative variants in several benchmarks and can identify novel pathogenic structural variants in consanguineous families. Availabilityhttps://github.com/bio-ontology-research-group/DeepSVP Contactrobert.hoehndorf@kaust.edu.sa

bioinformatics↗

bioRxiv2020

A single neuron subset governs a single coactive neuron circuit in Hydra vulgaris , representing a prototypic feature of neural evolution

The last common ancestor of Bilateria and Cnidaria is believed to be one of the first animals to develop a nervous system over 500 million years ago. Many of the genes involved in the neural function of the advanced nervous system in Bilateria are well conserved in Cnidaria1. Thus, Cnidarian representative species, Hydra, is considered to be a living fossil and a good model organism for the study of the putative primitive nervous system in its last common ancestor. The diffuse nervous system of Hydra consists of several peptidergic neuron subsets. However, the specific functions of these subsets remain unclear. Using calcium imaging, here we show that the neuron subsets that express neuropeptide, Hym-1762,3 function as motor neurons to evoke longitudinal contraction. We found that all neurons in a subset defined by the Hym-176 gene (Hym-176A) or its paralogs (Hym-176B) expression4 are excited simultaneously, which is then followed by longitudinal contraction. This indicates not only that these neuron subsets are motor neurons but also that a single molecularly defined neuron subset forms a single coactive motor circuit. This is in contrast with the Bilaterian nervous system, where a single molecularly defined neuron subset harbors multiple coactive circuits, showing a mixture of neurons firing with different timings5. Furthermore, we found that the two motor circuits, one expressing Hym-176B in the body column and the other expressing Hym-176A in the foot, are coordinately regulated to exert region-specific contraction. Our results demonstrate that one neuron subset is likely to form a monofunctional circuit as a minimum functional unit to build a more complex behavior in Hydra. We propose that this simple feature (one subset, one circuit, one function) found in Hydra is a fundamental trait of the primitive nervous system.

neuroscience↗

bioRxiv2020

Rapid Evolution of Plastic-degrading Enzymes Prevalent in the Global Ocean

Estimates of marine plastic stocks, a major threat to marine life (1), are far lower than expected from exponentially-increasing litter inputs, suggesting important loss factors (2, 3). These may involve microbial degradation, as the plastic-degrading polyethylene terephthalate enzyme (PETase) has been reported in marine microbial communities (4). An assessment of 416 metagenomes of planktonic communities across the global ocean identifies 68 oceanic PETase variants (oPETase) that evolved from ancestral enzymes degrading polycyclic aromatic hydrocarbons. Twenty oPETases show predicted efficiencies comparable to those of laboratory-optimized PETases, suggesting strong selective pressures directing the evolution of these enzymes. We found oPETases in 90.1% of samples across all oceans and depths, particularly abundant at 1,000 m depth, with a strong dominance of Pseudomonadales containing putative highly-efficient oPETase variants in the dark ocean. Enzymatic degradation may be removing plastic from the marine environment while providing a carbon source for bathypelagic microbial communities.

evolutionary biology↗

bioRxiv2020

Integrated metabolic modeling, culturing and transcriptomics explains enhanced virulence of V. cholerae during co-infection with ETEC

Gene essentiality is altered during polymicrobial infections. Nevertheless, most studies rely on single-species infections to assess pathogen gene essentiality. Here, we use genome-scale metabolic models to explore the effect of co-infection of the diarrheagenic pathogen Vibrio cholerae (V. cholerae) with another enteric pathogen, enterotoxigenic E. coli (ETEC). Model predictions showed that V. cholerae metabolic capabilities were increased due to ample cross-feeding opportunities enabled by ETEC. This is in line with increased severity of cholera symptoms known to occur in patients with dual-infections by the two pathogens. In vitro co-culture systems confirmed that V. cholerae growth is enhanced in co-cultures relative to single-cultures. Further, expression levels of several V. cholerae metabolic genes were significantly perturbed as shown by dual RNAseq analysis of its co-cultures with different ETEC strains. A decrease in ETEC growth was also observed, probably mediated by non-metabolic factors. Single gene essentiality analysis predicted conditionally-independent genes that are essential for the pathogen’s growth in both single- and co-infection scenarios. Our results reveal growth differences that are of relevance to drug targeting and efficiency in polymicrobial infections.Importance Most studies proposing new strategies to manage and treat infections have been largely focused on identifying druggable targets that can inhibit a pathogen’s growth when it is the single cause of infection. In vivo, however, infections can be caused by multiple species. This is important to take into account when attempting to develop or use current antibacterials since their efficacy can change significantly between single and co-infections. In this study, we used genome-scale metabolic models (GEMs) to interrogate the growth capabilities of Vibrio cholerae (V. cholerae) in single and co-infections with enterotoxigenic E. coli (ETEC), which co-occur in large fraction of diarrheagenic patients. Co-infection model predictions showed that V. cholerae growth capabilities are enhanced in presence of ETEC relative to V. cholerae single-infection, through cross-fed metabolites made available to V. cholerae by ETEC. In vitro, co-cultures of the two enteric pathogens further confirmed model predictions showing an increased growth of V. cholerae in co-culture relative to V. cholerae single-cultures while ETEC growth was suppressed. Dual RNAseq analysis of the co-cultures also confirmed that the transcriptome of V. cholerae is distinct during co-infection compared to single infection scenarios where processes related to metabolism were significantly perturbed. Further, in silico gene-knock out simulations uncovered discrepancies in gene essentiality for V. cholerae growth between single and co-infections. Integrative model-guided analysis thus identified druggable targets that would be critical for V. cholerae growth in both single and co-infections, thus designing inhibitors against those targets would provide a broader spectrum coverage against cholera infections.View Full Text

systems biology↗

bioRxiv2020

Massively parallel single-cell genome sequencing enables high-resolution analysis of soil and marine microorganisms

To improve our understanding of the environmental microbiome, we developed a single-cell genome sequencing platform, named SAG-gel, which utilizes gel beads for single-cell isolation, cell lysis, and whole genome amplification (WGA) for sequencing. SAG-gel enables serial, parallel and independent reactions of > 100,000 single cells in a single tube, delivering high-quality genome recovery with storable randomized single-cell genome libraries. From soil and marine environmental sources, we acquired 734 partial genomes that are recapitulated in 231 species, 35% of which were assigned as high-to-medium qualities. We found that each genome to be almost unique and 98.7% of them were newly identified, implying the complex genetic diversities across 44 phyla. The various metabolic capabilities including virulence factors and biosynthetic gene clusters were found across the lineages at single-cell resolution. This technology will accelerate the accumulation of reference genomes of uncharacterized environmental microbes and provide us new insights for their roles.

genomics↗

bioRxiv2020

Functional pangenome analysis provides insights into the origin, function and pathways to therapy of SARS-CoV-2 coronavirus

The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1-specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema in lungs causing the acute respiratory distress syndrome (ARDS)4-6, the leading cause of death in SARS-CoV-1 and SARS-CoV-2 infection7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.

genomics↗

bioRxiv2019

Machine Learning Reveals Spatiotemporal Genome Evolution in Asian Rice Domestication

Domestication is anthropogenic evolution that fulfills mankinds critical food demand. As such, elucidating the molecular mechanisms behind this process promotes the development of future new food resources including crops. With the aim of understanding the long-term domestication process of Asian rice and by employing the Oryza sativa subspecies (indica and japonica) as an Asian rice domestication model, we scrutinized past genomic introgressions between them as traces of domestication. Here we show the genome-wide introgressive region (IR) map of Asian rice, by utilizing 4,587 accession genotypes with a stable outgroup species, particularly at the finest resolution through a machine learning-aided method. The IR map revealed that 14.2% of the rice genome consists of IRs, including both wide IRs (recent) and narrow IRs (ancient). This introgressive landscape with their time calibration indicates that introgression events happened in multiple genomic regions over multiple periods. From the correspondence between our wide IRs and the so-called selective sweep regions, we provide a definitive answer to a long-standing controversy over the evolutionary origin of Asian rice domestication, single or multiple origins: It heavily depends upon which regions you pay attention to, implying that wider genomic regions represent immediate short history of Asian rice domestication as a likely support to the single origin, while its ancient history is interspersed in narrower traces throughout the genome as a possible support to the multiple origin.

plant biology↗

bioRxiv2019

Metabolic Architecture of the Deep Ocean Microbiome

The deep sea, the largest compartment of the ocean, is an essential component of the Earth system, but the functional exploration of its microbial communities lags far behind that of other marine realms. Here we analyze 58 bathypelagic microbial metagenomes from the Atlantic, Indian, and Pacific Oceans in an unprecedented sampling effort from the Malaspina Global Expedition, to resolve the metabolic architecture of the deep ocean microbiome. The Malaspina Deep-Sea Gene Collection, 71% of which consists of novel genes, reveals a strong dichotomy between the functional traits of free-living and particle-attached microorganisms, and shows relatively patchy composition challenging the paradigm of a uniform dark ocean ecosystem. Metagenome Assembled Genomes uncovered 11 potential new phyla, establishing references for deep ocean microbial taxa, and revealed mixotrophy to be a widespread trophic strategy in the deep ocean. These results expand our understanding of the functional diversity, metabolic versatility, and carbon cycling in the largest ecosystem on Earth.\n\nOne Sentence SummaryA whole community genomic survey of the deep microbiome sheds light on the microbial and functional diversity of the dark ocean.

microbiology↗

bioRxiv2019

Ontology-based prediction of cancer driver genes

Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity, many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.

bioinformatics↗

bioRxiv2018

Finding Nemo’s Genes: A chromosome-scale reference assembly of the genome of the orange clownfish Amphiprion percula

The iconic orange clownfish, Amphiprion percula, is a model organism for studying the ecology and evolution of reef fishes, including patterns of population connectivity, sex change, social organization, habitat selection and adaptation to climate change. Notably, the orange clownfish is the only reef fish for which a complete larval dispersal kernel has been established and was the first fish species for which it was demonstrated that anti-predator responses of reef fishes could be impaired by ocean acidification. Despite its importance, molecular resources for this species remain scarce and until now it lacked a reference genome assembly. Here we present a de novo chromosome-scale assembly of the genome of the orange clownfish Amphiprion percula. We utilized single-molecule real-time sequencing technology from Pacific Biosciences to produce an initial polished assembly comprised of 1,414 contigs, with a contig N50 length of 1.86 Mb. Using Hi-C based chromatin contact maps, 98% of the genome assembly were placed into 24 chromosomes, resulting in a final assembly of 908.8 Mb in length with contig and scaffold N50s of 3.12 and 38.4 Mb, respectively. This makes it one of the most contiguous and complete fish genome assemblies currently available. The genome was annotated with 26,597 protein coding genes and contains 96% of the core set of conserved actinopterygian orthologs. The availability of this reference genome assembly as a community resource will further strengthen the role of the orange clownfish as a model species for research on the ecology and evolution of reef fishes.

genomics↗

bioRxiv2017

TOWARDS A GLOBAL SUPPORT OF CORE DATA RESOURCES FOR THE LIFE SCIENCES

On November 18-19, 2016, the Human Frontier Science Program Organization (HFSPO) hosted a meeting of senior managers of key data resources and leaders of several major funding organizations to discuss the challenges associated with sustaining biological and biomedical (i.e., life sciences) data resources and associated infrastructure. A strong consensus emerged from the group that core data resources for the life sciences should be supported through a coordinated international effort(s) that better ensure long-term sustainability and that appropriately align funding with scientific impact. Ideally, funding for such data resources should allow for access at no charge, as is presently the usual (and preferred) mechanism. Below, the rationale for this vision is described, and some important considerations for developing a new international funding model to support core data resources for the life sciences are presented.

scientific communication and education↗