The crown-of-thorns starfish genome as a guide for biocontrol of this coral reef pest.

The crown-of-thorns starfish (COTS, the Acanthaster planci species group) is a highly fecund predator of reef-building corals throughout the Indo-Pacific region. COTS population outbreaks cause substantial loss of coral cover, diminishing the integrity and resilience of reef ecosystems. Here we sequenced genomes of COTS from the Great Barrier Reef, Australia and Okinawa, Japan to identify gene products that underlie species-specific communication and could potentially be used in biocontrol strategies. We focused on water-borne chemical plumes released from aggregating COTS, which make the normally sedentary starfish become highly active. Peptide sequences detected in these plumes by mass spectrometry are encoded in the COTS genome and expressed in external tissues. The exoproteome released by aggregating COTS consists largely of signalling factors and hydrolytic enzymes, and includes an expanded and rapidly evolving set of starfish-specific ependymin-related proteins. These secreted proteins may be detected by members of a large family of olfactory-receptor-like G-protein-coupled receptors that are expressed externally, sometimes in a sex-specific manner. This study provides insights into COTS-specific communication that may guide the generation of peptide mimetics for use on reefs with COTS outbreaks.

Eighteen Coral Genomes Reveal the Evolutionary Origin of Acropora Strategies to Accommodate Environmental Changes.

The genus Acropora comprises the most diverse and abundant scleractinian corals (Anthozoa, Cnidaria) in coral reefs, the most diverse marine ecosystems on Earth. However, the genetic basis for the success and wide distribution of Acropora are unknown. Here, we sequenced complete genomes of 15 Acropora species and 3 other acroporid taxa belonging to the genera Montipora and Astreopora to examine genomic novelties that explain their evolutionary success. We successfully obtained reasonable draft genomes of all 18 species. Molecular dating indicates that the Acropora ancestor survived warm periods without sea ice from the mid or late Cretaceous to the Early Eocene and that diversification of Acropora may have been enhanced by subsequent cooling periods. In general, the scleractinian gene repertoire is highly conserved; however, coral- or cnidarian-specific possible stress response genes are tandemly duplicated in Acropora. Enzymes that cleave dimethlysulfonioproprionate into dimethyl sulfide, which promotes cloud formation and combats greenhouse gasses, are the most duplicated genes in the Acropora ancestor. These may have been acquired by horizontal gene transfer from algal symbionts belonging to the family Symbiodiniaceae, or from coccolithophores, suggesting that although functions of this enzyme in Acropora are unclear, Acropora may have survived warmer marine environments in the past by enhancing cloud formation. In addition, possible antimicrobial peptides and symbiosis-related genes are under positive selection in Acropora, perhaps enabling adaptation to diverse environments. Our results suggest unique Acropora adaptations to ancient, warm marine environments and provide insights into its capacity to adjust to rising seawater temperatures.

Hemichordate genomes and deuterostome origins.

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.

Diagnostic performance of peripheral leukocyte telomere G-tail length for detecting breast cancer.

The telomere G-tail (G-tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G-tail length of breast cancer (BC) patients and cancer-free individuals and evaluated the association between the G-tail length and the presence of BC. A significant shortening of the median G-tail length was observed in BC patients compared with cancer-free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G-tail length might be a potential biomarker for BC detection.

Correction to: A new species of Xenoturbella from the western Pacific Ocean and the evolution of Xenoturbella.

After publication of Nakano et al. (2017) [1], the authors became aware of the fact that the new species-group name erected for the two specimens of a Japanese xenoturbellid species in the article is not available because Nakano et al. (2017) [1] does not meet the requirement of the amendment of Article 8.5.3 of the International Code of Zoological Nomenclature (the Code) [2]. The authors therefore describe the two xenoturbellids as a new species again in this correction article. Methods for morphological observation, DNA extraction and sequencing were as described in Nakano et al. (2017) [1]. The holotype and paratype specimens are deposited in the National Museum of Nature and Science, Tsukuba (NSMT), Japan. The DNA sequences obtained were deposited in the International Nucleotide Sequence Database (INSD).

A draft genome of the striped catfish, Pangasianodon hypophthalmus, for comparative analysis of genes relevant to development and a resource for aquaculture improvement.

BACKGROUND: The striped catfish, Pangasianodon hypophthalmus, is a freshwater and benthopelagic fish common in the Mekong River delta. Catfish constitute a valuable source of dietary protein. Therefore, they are cultured worldwide, and P. hypophthalmus is a food staple in the Mekong area. However, genetic information about the culture stock, is unavailable for breeding improvement, although genetics of the channel catfish, Ictalurus punctatus, has been reported. To acquire genome sequence data as a useful resource for marker-assisted breeding, we decoded a draft genome of P. hypophthalmus and performed comparative analyses. RESULTS: Using the Illumina platform, we obtained both nuclear and mitochondrial DNA sequences. Molecular phylogeny using the mitochondrial genome confirmed that P. hypophthalmus is a member of the family Pangasiidae and is nested within a clade including the families Cranoglanididae and Ictaluridae. The nuclear genome was estimated at approximately 700 Mb, assembled into 568 scaffolds with an N50 of 14.29 Mbp, and was estimated to contain ~ 28,600 protein-coding genes, comparable to those of channel catfish and zebrafish. Interestingly, zebrafish produce gadusol, but genes for biosynthesis of this sunscreen compound have been lost from catfish genomes. The differences in gene contents between these two catfishes were found in genes for vitamin D-binding protein and cytosolic phospholipase A2, which have lost only in channel catfish. The Hox cluster in catfish genomes comprised seven paralogous groups, similar to that of zebrafish, and comparative analysis clarified catfish lineage-specific losses of A5a, B10a, and A11a. Genes for insulin-like growth factor (IGF) signaling were conserved between the two catfish genomes. In addition to identification of MHC class I and sex determination-related gene loci, the hypothetical chromosomes by comparison with the channel catfish demonstrated the usefulness of the striped catfish genome as a marker resource. CONCLUSIONS: We developed genomic resources for the striped catfish. Possible conservation of genes for development and marker candidates were confirmed by comparing the assembled genome to that of a model fish, Danio rerio, and to channel catfish. Since the catfish genomic constituent resembles that of zebrafish, it is likely that zebrafish data for gene functions is applicable to striped catfish as well.

A new species of Xenoturbella from the western Pacific Ocean and the evolution of Xenoturbella.

BACKGROUND: Xenoturbella is a group of marine benthic animals lacking an anus and a centralized nervous system. Molecular phylogenetic analyses group the animal together with the Acoelomorpha, forming the Xenacoelomorpha. This group has been suggested to be either a sister group to the Nephrozoa or a deuterostome, and therefore it may provide important insights into origins of bilaterian traits such as an anus, the nephron, feeding larvae and centralized nervous systems. However, only five Xenoturbella species have been reported and the evolutionary history of xenoturbellids and Xenacoelomorpha remains obscure. RESULTS: Here we describe a new Xenoturbella species from the western Pacific Ocean, and report a new xenoturbellid structure - the frontal pore. Non-destructive microCT was used to investigate the internal morphology of this soft-bodied animal. This revealed the presence of a frontal pore that is continuous with the ventral glandular network and which exhibits similarities with the frontal organ in acoelomorphs. CONCLUSIONS: Our results suggest that large size, oval mouth, frontal pore and ventral glandular network may be ancestral features for Xenoturbella. Further studies will clarify the evolutionary relationship of the frontal pore and ventral glandular network of xenoturbellids and the acoelomorph frontal organ. One of the habitats of the newly identified species is easily accessible from a marine station and so this species promises to be valuable for research on bilaterian and deuterostome evolution.

Evolutionary affinities of the unfathomable Parabrotulidae: Molecular data indicate placement of Parabrotula within the family Bythitidae, Ophidiiformes.

Fishes are widely diverse in shape and body size and can quite rapidly undergo these changes. Consequently, some relationships are not clearly resolved with morphological analyses. In the case of fishes of small body size, informative characteristics can be absent due to simplification of body structures. The Parabrotulidae, a small family of diminutive body size consisting of two genera and three species has most recently been classified as either a perciform within the suborder Zoarcoidei or an ophidiiform. Classification of parabrotulids as ophidiiforms has become predominant; however the Parabrotulidae has not yet been investigated in a molecular phylogenetic framework. We examine molecular data from ten genetic loci to more specifically place the Parabrotulidae within the fish tree of life. In a hypothesis testing framework, the Parabrotulidae as a zoarcoid taxon is rejected. Previous identity with zoarcoids due to the one fin ray for each vertebra being present, a characteristic for the Zoarcidae, appears to be an example of convergence. Our results indicate that parabrotulids are viviparous ophidiiforms within the family Bythitidae.

Retinoic acid-driven Hox1 is required in the epidermis for forming the otic/atrial placodes during ascidian metamorphosis.

Retinoic acid (RA)-mediated expression of the homeobox gene Hox1 is a hallmark of the chordate central nervous system (CNS). It has been suggested that the RA-Hox1 network also functions in the epidermal ectoderm of chordates. Here, we show that in the urochordate ascidian Ciona intestinalis, RA-Hox1 in the epidermal ectoderm is necessary for formation of the atrial siphon placode (ASP), a structure homologous to the vertebrate otic placode. Loss of Hox1 function resulted in loss of the ASP, which could be rescued by expressing Hox1 in the epidermis. As previous studies showed that RA directly upregulates Hox1 in the epidermis of Ciona larvae, we also examined the role of RA in ASP formation. We showed that abolishment of RA resulted in loss of the ASP, which could be rescued by forced expression of Hox1 in the epidermis. Our results suggest that RA-Hox1 in the epidermal ectoderm played a key role in the acquisition of the otic placode during chordate evolution.

Retinoid X receptor-mediated transdifferentiation cascade in budding tunicates.

In the budding tunicate, Polyandrocarpa misakiensis, retinoic acid (RA) applied to buds promotes transdifferentiation of somatic cells to form the secondary body axis. This study investigated the gene cascade regulating such RA-triggered transdifferentiation in tunicates. Genes encoding retinoic acid receptor (RAR) and retinoid X receptor (RXR) were induced during transdifferentiation, and they responded to all-trans RA or 13-cis RA in vivo, whereas 9-cis RA had the least effects, demonstrating differences in the ligand preference between budding tunicates and vertebrates. In contrast to RAR mRNA, RXR mRNA could induce transdifferentiation-related genes such as RXR itself, ERK, and MYC in an RA-dependent manner and also induced ß-catenin (ß-CTN) RA-independently when it was introduced in vitro into tunicate cell lines that do not express endogenous RAR or RXR. Small interfering RNA (siRNA) of RXR dramatically attenuated not only RXR but also ERK and ß-CTN gene activities. An ERK inhibitor severely blocked wound healing and dedifferentiation. ß-CTN siRNA suppressed morphogenesis and redifferentiation, similar to RXR siRNA. These results indicate that in P. misakiensis, the main function of RA is to trigger positive feedback regulation of RXR rather than to activate RAR for unlocking downstream pathways for transdifferentiation. Our results may reflect an ancient mode of RA signaling in chordates.

Long-read genome assembly of the Japanese parasitic wasp Copidosoma floridanum (Hymenoptera: Encyrtidae).

Copidosoma floridanum is a cosmopolitan species and an egg-larval parasitoid of the Plusiine moth. C. floridanum has a unique development mode called polyembryony, in which over two thousands of genetically identical embryos are produced from a single egg. Some embryos develop into sterile soldier larvae precociously, and their emergence period and aggressive behavior are differed between the US and Japanese C. floridanum strains. Genome sequencing expects to contribute our understanding of the molecular bases underlying progression of polyembryony. However, only the genome sequence of the US strain from generating by short-read assembly has been reported. In the present study, we determined the genome sequence of the Japanese strain using Pacific Biosciences high-fidelity reads and generating a highly contiguous assembly (552.7 Mb, N50: 17.9 Mb). Gene prediction and annotation identified 13,886 transcripts derived from 10,786 gene models. We searched the genomic differences between US and Japanese strains. Among gene models predicted in this study, 100 gene loci in the Japanese strain had extremely different gene structure from those in the US strain. This was accomplished through the functional annotation (GGSEARCH) and long-read sequencing. Genomic differences between strains were also reflected to amino acid sequences of vasa that plays a central role in caste determination in this species. The genome assemblies constructed in this study will facilitate the genomic comparisons between Japanese and US strains, leading to our understanding of detail genomic regions responsible for the ecological and physiological characters of C. floridanum.

Identification of a retinoic acid-responsive neural enhancer in the Ciona intestinalis Hox1 gene.

The Hox1 gene in the urochordate ascidian Ciona intestinalis (Ci-Hox1) is expressed in the nerve cord and epidermis. We identified a nerve cord enhancer in the second intron of Ci-Hox1, and demonstrated that retinoic acid (RA) plays a major role in activating this enhancer. The enhancer contained a putative retinoic acid-response element (RARE). Mutation of the RARE in the Ci-Hox1 nerve cord enhancer only partially abolished the enhancer activity. Genes encoding RA synthase and the RA receptor were knocked down using specific antisense morpholino oligos (MOs), and injection of embryos with these MOs resulted in the complete disappearance of epidermal expression of Ci-Hox1 and reduction of neural expression. However, nerve cord expression was not completely repressed. These results suggest that the nerve cord enhancer is activated by two partially redundant pathways; one RA-dependent and one RA-independent.

Association Between Telomere G-Tail Length and Coronary Artery Disease or Statin Treatment in Patients With Cardiovascular Risks　- A Cross-Sectional Study.

Background: The utility of telomere G-tail length to predict coronary artery disease (CAD) remains controversial. CAD results from coronary artery narrowing due to cholesterol and lipid accumulation, augmented by inflammatory cells and other factors. This study explored the significance of telomere G-tail length in suspected CAD patients. Methods and Results: In all, 95 patients with suspected CAD or ≥1 cardiac risk factor underwent coronary computed tomography angiography (CCTA). We measured leukocyte telomere length and G-tail length using a hybrid protection method, and diagnosed the presence of CAD using CCTA. Associations between G-tail length and the presence of CAD, the number of stenosed coronary arteries, and brachial-ankle pulse wave velocity (baPWV) were analyzed. No significant difference was observed in G-tail length when comparing groups with or without CAD or statin treatment. However, in the non-statin group, G-tail length was significantly shorter in patients with 3-vessel disease compared with 1-vessel disease. Dividing the group using a baPWV of 1,300 cm/s, telomere G-tail length was significantly shorter in the high-risk (baPWV ≥1,300 cm/s) group. Conclusions: The clinical utility of telomere G-tail length as a CAD risk indicator seems limited. There was a trend for longer telomere G-tail length in the statin-treated group. Moreover, telomere G-tail length was reduced in patients at high-risk of cardiovascular events, aligning with the trend of a shortening in telomere G-tail length with CAD severity.

Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants.

The decrease of antibody efficacy to mutated SARS-CoV-2 spike RBD explains the breakthrough infections and reinfections by Omicron variants. Here, we analyzed broadly neutralizing antibodies isolated from long-term hospitalized convalescent patients of early SARS-CoV-2 strains. One of the antibodies named NCV2SG48 is highly potent to broad SARS-CoV-2 variants including Omicron BA.1, BA.2, and BA.4/5. To reveal the mode of action, we determined the sequence and crystal structure of the Fab fragment of NCV2SG48 in a complex with spike RBD from the original, Delta, and Omicron BA.1. NCV2SG48 is from a minor VH but the multiple somatic hypermutations contribute to a markedly extended binding interface and hydrogen bonds to interact with conserved residues at the core receptor-binding motif of RBD, which efficiently neutralizes a broad spectrum of variants. Thus, eliciting the RBD-specific B cells to the longitudinal germinal center reaction confers potent immunity to broad SARS-CoV-2 variants emerging one after another.

Whole-Genome Sequencing Highlights Conservative Genomic Strategies of a Stress-Tolerant, Long-Lived Scleractinian Coral, Porites australiensis Vaughan, 1918.

Massive corals of the genus Porites, common, keystone reef builders in the Indo-Pacific Ocean, are distinguished by their relative stress tolerance and longevity. In order to identify genetic bases of these attributes, we sequenced the complete genome of a massive coral, Porites australiensis. We developed a genome assembly and gene models of comparable quality to those of other coral genomes. Proteome analysis identified 60 Porites skeletal matrix protein genes, all of which show significant similarities to genes from other corals and even to those from a sea anemone, which has no skeleton. Nonetheless, 30% of its skeletal matrix proteins were unique to Porites and were not present in the skeletons of other corals. Comparative genomic analyses showed that genes widely conserved among other organisms are selectively expanded in Porites. Specifically, comparisons of transcriptomic responses of P. australiensis and Acropora digitifera, a stress-sensitive coral, reveal significant differences in regard to genes that respond to increased water temperature, and some of the genes expanded exclusively in Porites may account for the different thermal tolerances of these corals. Taken together, widely shared genes may have given rise to unique biological characteristics of Porites, massive skeletons and stress tolerance.

Whole-Genome Transcriptome Analyses of Native Symbionts Reveal Host Coral Genomic Novelties for Establishing Coral-Algae Symbioses.

Reef-building corals and photosynthetic, endosymbiotic algae of the family Symbiodiniaceae establish mutualistic relationships that are fundamental to coral biology, enabling coral reefs to support a vast diversity of marine species. Although numerous types of Symbiodiniaceae occur in coral reef environments, Acropora corals select specific types in early life stages. In order to study molecular mechanisms of coral-algal symbioses occurring in nature, we performed whole-genome transcriptomic analyses of Acropora tenuis larvae inoculated with Symbiodinium microadriaticum strains isolated from an Acropora recruit. In order to identify genes specifically involved in symbioses with native symbionts in early life stages, we also investigated transcriptomic responses of Acropora larvae exposed to closely related, nonsymbiotic, and occasionally symbiotic Symbiodinium strains. We found that the number of differentially expressed genes was largest when larvae acquired native symbionts. Repertoires of differentially expressed genes indicated that corals reduced amino acid, sugar, and lipid metabolism, such that metabolic enzymes performing these functions were derived primarily from S. microadriaticum rather than from A. tenuis. Upregulated gene expression of transporters for those metabolites occurred only when coral larvae acquired their natural symbionts, suggesting active utilization of native symbionts by host corals. We also discovered that in Acropora, genes for sugar and amino acid transporters, prosaposin-like, and Notch ligand-like, were upregulated only in response to native symbionts, and included tandemly duplicated genes. Gene duplications in coral genomes may have been essential to establish genomic novelties for coral-algae symbiosis.

Epidermal expression of Hox1 is directly activated by retinoic acid in the Ciona intestinalis embryo.

Hox genes play important roles in the specification of spatial identity during development of vertebrate embryos. Retinoic acid regulates the transcription of Hox genes in vertebrates. We identified an epidermal enhancer in the 5' flanking region of an ortholog of Hox1 (Ci-Hox1) in the ascidian Ciona intestinalis. This enhancer element drives the transcription of a lacZ reporter gene in the epidermis in the posterior trunk and the anterior tail region of tailbud-stage embryos. Inhibition of retinoic acid synthesis resulted in inactivation of the expression of the reporter gene. The enhancer contains a putative retinoic acid response element. When this element was mutagenized, the expression of the reporter gene disappeared from the epidermis. This sequence was also required for the response to exogenously administered retinoic acid. A heterodimeric nuclear receptor, consisting of the retinoic acid receptor and retinoid X receptor, bound to this sequence. These results indicate that retinoic acid directly activates the epidermal enhancer of Ci-Hox1. This is the first demonstration that retinoic acid is necessary for endogenous gene expression in ascidian embryos.

Dicyemid Mesozoans: A Unique Parasitic Lifestyle and a Reduced Genome.

Dicyemids, previously called "mesozoans" (intermediates between unicellular protozoans and multicellular metazoans), are an enigmatic animal group. They have a highly simplified adult body, comprising only ∼30 cells, and they have a unique parasitic lifestyle. Recently, dicyemids were shown to be spiralians, with affinities to the Platyhelminthes. In order to understand molecular mechanisms involved in evolution of this odd animal, we sequenced the genome of Dicyema japonicum and a reference transcriptome assembly using mixed-stage samples. The D. japonicum genome features a high proportion of repetitive sequences that account for 49% of the genome. The dicyemid genome is reduced to ∼67.5 Mb with 5,012 protein-coding genes. Only four Hox genes exist in the genome, with no clustering. Gene distribution in KEGG pathways shows that D. japonicum has fewer genes in most pathways. Instead of eliminating entire critical metabolic pathways, parasitic lineages likely simplify pathways by eliminating pathway-specific genes, while genes with fundamental functions may be retained in multiple pathways. In principle, parasites can stand to lose genes that are unnecessary, in order to conserve energy. However, whether retained genes in incomplete pathways serve intermediate functions and how parasites overcome the physiological needs served by lost genes, remain to be investigated in future studies.

A draft nuclear-genome assembly of the acoel flatworm Praesagittifera naikaiensis.

BACKGROUND: Acoels are primitive bilaterians with very simple soft bodies, in which many organs, including the gut, are not developed. They provide platforms for studying molecular and developmental mechanisms involved in the formation of the basic bilaterian body plan, whole-body regeneration, and symbiosis with photosynthetic microalgae. Because genomic information is essential for future research on acoel biology, we sequenced and assembled the nuclear genome of an acoel, Praesagittifera naikaiensis. FINDINGS: To avoid sequence contamination derived from symbiotic microalgae, DNA was extracted from embryos that were free of algae. More than 290x sequencing coverage was achieved using a combination of Illumina (paired-end and mate-pair libraries) and PacBio sequencing. RNA sequencing and Iso-Seq data from embryos, larvae, and adults were also obtained. First, a preliminary ∼17-kilobase pair (kb) mitochondrial genome was assembled, which was deleted from the nuclear sequence assembly. As a result, a draft nuclear genome assembly was ∼656 Mb in length, with a scaffold N50 of 117 kb and a contig N50 of 57 kb. Although ∼70% of the assembled sequences were likely composed of repetitive sequences that include DNA transposons and retrotransposons, the draft genome was estimated to contain 22,143 protein-coding genes, ∼99% of which were substantiated by corresponding transcripts. We could not find horizontally transferred microalgal genes in the acoel genome. Benchmarking Universal Single-Copy Orthologs analyses indicated that 77% of the conserved single-copy genes were complete. Pfam domain analyses provided a basic set of gene families for transcription factors and signaling molecules. CONCLUSIONS: Our present sequencing and assembly of the P. naikaiensis nuclear genome are comparable to those of other metazoan genomes, providing basic information for future studies of genic and genomic attributes of this animal group. Such studies may shed light on the origins and evolution of simple bilaterians.