ABSTRACT Global aquaculture production has been rising for several decades, with up to 76% of the total production from fish. However, the problem of fish diseases is becoming more and more prominent in today's context of pursuing sustainable aquaculture. Since the first fish genome assembly reported in 2002, genomic approaches have been successfully implemented in fish breeding to enhance disease resistance and reduce economic losses caused by diverse fish diseases. Here, we present a review of the current progress in fish genomics and its application in disease‐resistance breeding. First, assembly data for all publicly available fish genomes were curated and statistical analysis of these data were performed. Subsequently, genomics‐assisted breeding approaches (including quantitative trait loci mapping, genome‐wide association study, marker‐assisted selection, genomic selection, gene transfer, and genome editing) that have been applied in practical disease–resistance breeding programs are outlined. In addition, candidate genetic markers that could possibly be utilized in breeding were summarized. Finally, remaining challenges and further directions were discussed. In summary, this review provides insight into fish genomics and genomics‐assisted breeding of disease‐resistant fish varieties. 

Fish Genomics and Its Application in Disease‐Resistance Breeding

Decoding the fish genome opens a new era in important trait research and molecular breeding in China.

Nuclear factor kappa-B (NF-κB) pathway is a key mediator of inflammation response that plays a role in host defense for pathogen elimination, but excessive activation may lead to tissue damage or pathogen transmission. The negative regulation of NF-κB in lower vertebrates is largely unknown, hindering further understanding of immune signaling evolution. Here, we provided evidence that Epinephelus coioides soluble toll-like receptor 5 (TLR5S), a member of the TLR5 subfamily, has been newly identified as a negative regulator of NF-κB signaling. EcTLR5S was a cytoplasmic protein consisting of 17 leucine-rich repeat domains, which specifically responded to Vibrio flagellin and suppressed flagellin-induced NF-κB signaling activation and cytokine expression. The amino-terminal LRR 1–5 region was necessary for its negative regulatory function. Dual-luciferase reporter assay showed that EcTLR5S significantly inhibited the NF-κB-luc activity induced by inhibitor of NF-κB kinase α (IKKα) and IKKβ. Subsequently, the functional relationship between EcTLR5M and EcTLR5S was analyzed, revealing that the negative regulatory function of EcTLR5S targeted the activation of the NF-κB pathway mediated by EcTLR5M. The above results reveal that EcTLR5S negatively regulates the flagellin-induced EcTLR5M-NF-κB pathway activation, which may prevent over-activation of immune signaling and restore homeostasis. 

TLR5S negatively regulates the TLR5M-mediated NF-κB signaling pathway in Epinephelus coioides.

Leopard coral grouper (Plectropomus leopardus) is a type of hermaphrodite fish, but the mechanisms of gonadal development and gametogenesis remain unclear. In the present study, we performed histological observation and transcriptomic analysis during the process of sexual differentiation in P. leopardus. According to the histological results, sexual differentiation was completed at 15 months old, developed synchronously in male and female individuals at 2 years old, and matured synchronously at 3 years old. Comparative transcriptomic analyses showed that the gonadal had differentiated by 15 months old, with enrichment of pathways associated with cell proliferation, transcriptional metabolism, and germline stem cell differentiation. Furthermore, cilium movement and fatty acid anabolism, which are associated with spermatogenesis and oocyte growth, were significantly enriched at 3 years old. In addition, key genes associated with male and female sex differentiation, such as amh, dmrt1, dmrt2a, zp4, sox3, gdf9, and gsdf, were identified by weighted gene co-expression network analysis (WGCNA). Finally, the localization and expression of the key genes amh and sox3 were observed in different cell types within the testes and ovaries, reflecting the development of the testes and ovaries, respectively. All the evidence indicates that P. leopardus is a hermaphrodite and synchronously sexually mature fish. Our study complements the gonadal development patterns of hermaphroditic fish by providing new insights into the molecular mechanisms underlying sexual differentiation and sex change in hermaphroditic groupers. 

Synchronously sexual maturity in hermaphrodite fish as revealed by transcriptome analysis in Plectropomus leopardus.

Transcriptome and hypoxia-responsive gene expression analyses reveal the physiological reaction to acute hypoxia and reoxygenation in Epinephelus coioides

Most grouper species are functional protogynous hermaphrodites, but the genetic basis and the molecular mechanisms underlying the regulation of this unique reproductive strategy remain enigmatic. In this study, we report a high‐quality chromosome‐level genome assembly of the representative orange‐spotted grouper (Epinephelus coioides). No duplication or deletion of sex differentiation‐related genes was found in the genome, suggesting that sex development in this grouper may be related to changes in regulatory sequences or environmental factors. Transcriptomic analyses showed that aromatase and retinoic acid are probably critical to promoting ovarian fate determination, and follicle‐stimulating hormone triggers the female‐to‐male sex change. Socially controlled sex‐change studies revealed that, in sex‐changing fish, the brain's response to the social environment may be mediated by activation of the phototransduction cascade and the melatonin synthesis pathway. In summary, our genomic and experimental results provide novel insights into the molecular mechanisms of sex differentiation and sex change in the protogynous groupers.

Mechanisms of sex differentiation and sex reversal in hermaphrodite fish as revealed by the Epinephelus coioides genome

With current and future leading systems adopting heterogeneous architectures, adapting existing models for heterogeneous supercomputers is of urgent need for improving model resolution and reducing modeling uncertainty. This paper presents our three-week effort on porting a complex earth system model, CESM 2.2, to a 40-million-core Sunway supercomputer. Taking a non-intrusive approach that tries to minimizes manual code modifications, our project tries to achieve both improvement of performance and consistency of the model code. By using a hierarchical grid system and an OpenMP-based offloading toolkit, our porting and parallelization effort covers over 80% of the code, and achieves a simulation speed of 340 SDPD (simulated days per day) for 5-km atmosphere, 265 SDPD for 3-km ocean, and 222 SDPD for a coupled model, thus making multi-year or even multi-decadal experiments at such high resolution possible.

Kilometer-Level Coupled Modeling Using 40 Million Cores: An Eight-Year Journey of Model Development

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Mechanisms of sex differentiation and sex reversal in hermaphrodite fish as revealed by the Epinephelus coioides genome

Kilometer-Level Coupled Modeling Using 40 Million Cores: An Eight-Year Journey of Model Development