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Freeze tolerance, the ability of an organism to survive internal ice formation, is a striking survival strategy employed by some ectotherms living in cold environments. However, the genetic bases of this remarkable adaptation are largely unknown. The Amur sleeper (Perccottus glenii), the only known freeze-tolerant fish species, can overwinter with its entire body frozen in ice. Here, we sequenced the chromosome-level genome of the Amur sleeper and performed comparative genomic, transcriptomic, and metabolomic analyses to investigate its strategies for surviving freezing. Evolutionary analysis suggested that the Amur sleeper diverged from its closest non-cold-hardy relative about 15.07 million years ago and has experienced a high rate of protein evolution. Transcriptomic and metabolomic data identified a coordinated and tissue-specific regulation of genes and metabolites involved in hypometabolism, cellular stress response, and cryoprotectant accumulation involved in freezing and thawing. Several genes show evidence of accelerated protein sequence evolution or family size expansion were found as adaptive responses to freezing-induced stresses. Specifically, genetic changes associated with cytoskeleton stability, cryoprotectant synthesis, transmembrane transport, and neuroprotective adaptations were identified as potentially key innovations that aid in freezing survival. Our work provides valuable resources and opportunities to unveil the molecular adaptations supporting freeze tolerance in ectothermic vertebrates.
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Gelo , Perciformes , Animais , Congelamento , Multiômica , Vertebrados , Adaptação Fisiológica/fisiologia , Aclimatação/genéticaRESUMO
BACKGROUND: Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated. METHODS: The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells. RESULTS: The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model. CONCLUSIONS: This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.
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Movimento Celular , Mitocôndrias , Pré-Eclâmpsia , Receptores Acoplados a Proteínas G , Trofoblastos , Regulação para Cima , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Humanos , Gravidez , Feminino , Mitocôndrias/metabolismo , Regulação para Cima/genética , Trofoblastos/metabolismo , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Movimento Celular/genética , Lectinas/metabolismo , Placenta/metabolismo , Camundongos , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Antígenos de Diferenciação de Linfócitos B/genética , AdultoRESUMO
BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.
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Fatores de Crescimento de Fibroblastos , Humanos , Masculino , Feminino , Fatores de Crescimento de Fibroblastos/genética , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética , Sistema Nervoso Simpático/fisiopatologia , Sistema Nervoso Simpático/patologia , Idoso , Linhagem , Expansão das Repetições de Trinucleotídeos/genética , Sequências de Repetição em Tandem/genética , Degenerações EspinocerebelaresRESUMO
The noncovalent interactions between formamide (FM) and the heteroaromatic compounds (furan and thiophene) were investigated through microwave spectroscopy and theoretical calculations. Each of the investigated complexes exhibits a single rotational spectrum corresponding to the lowest energy structure predicted theoretically. In the detected structures, N-H···O and C-H···O hydrogen bonds dominate the complexation between FM and furan, resulting in a planar configuration. Conversely, a superposed configuration linked by a N-H···π hydrogen bond and CâO···π contact is observed for the FM-thiophene complex. In both cases, hydrogen bonding interactions with N-H as proton donor rank as the dominant forces, and the interaction energy of N-H···O is larger than that of N-H···π. It was found that the electrostatic component is the largest contributor to the attraction between FM and furan, while the dispersion component is the most significant attractive factor in the FM-thiophene complex. These findings highlight the distinct features of hydrogen bonding interactions of amides with heteroaromatics in the studied complexes.
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The C-Hâ¯S-S interactions are fundamentally important to understand the stability of biomacromolecules and their binding with small molecules, but they are still underappreciated. Herein, we characterized the C-Hâ¯S-S interactions in model molecular complexes. The rotational spectra of the complexes of diethyl disulfide with CH2CH2 and CH2CHF were measured and analyzed. All the detected structures are mainly stabilized by a C-Hâ¯S-S hydrogen bond, providing stabilization energies of 2.3-7.2 kJ mol-1. Incidental C-Hâ¯π or C-Hâ¯F interactions enhance the stabilization of the complexes. London dispersion, which accounts for 54%-68% of the total attractions, is the main driving force of stabilization. The provided bonding features of C-Hâ¯S-S are crucial for understanding the stabilizing role of this type of interaction in diverse processes such as supramolecular recognition, protein stability, and enzyme activity.
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Cervical cancer is a significant global health issue primarily caused by high-risk types of human papillomavirus (HPV). Recent studies have reported an association between Trichomonas vaginalis (T. vaginalis) infections and HPV infections, highlighting the importance of simultaneously detecting these pathogens for effective cervical cancer risk management. However, current methods for detecting both T. vaginalis and HPV are limited. In this study, we present a novel approach using a microfluidic-chip-based system with loop-mediated isothermal amplification (LAMP) for the rapid and parallel detection of T. vaginalis, HPV16, HPV18, and HPV52 in a reagent-efficient and user-friendly manner. Compared to conventional LAMP assays in tubes, our system exhibits enhanced sensitivity with values of 2.43 × 101, 3.00 × 102, 3.57 × 101, and 3.60 × 102 copies per reaction for T. vaginalis, HPV16, HPV18, and HPV52, respectively. Additionally, we validated the performance of our chip by testing 47 clinical samples, yielding results consistent with the diagnostic methods used by the hospital. Therefore, our system not only offers a promising solution for concurrent diagnosis of T. vaginalis and HPV infections, particularly in resource-limited areas, due to its cost-effectiveness, ease of use, and rapid and accurate detection performance, but can also contribute to future research on the co-infection of these two pathogens. Moreover, the system possesses the capability to simultaneously detect up to 22 different types of pathogens, making it applicable across a wide range of domains such as diagnostics, food safety, and water monitoring.
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Infecções por Papillomavirus , Trichomonas vaginalis , Neoplasias do Colo do Útero , Feminino , Humanos , Trichomonas vaginalis/genética , Papillomavirus Humano , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Microfluídica , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Papillomavirus Humano 16 , Papillomavirus Humano 18/genéticaRESUMO
Recombinase polymerase amplification (RPA) is a useful pathogen identification method. Several label-free detection methods for RPA amplicons have been developed in recent years. However, these methods still lack sensitivity, specificity, efficiency, or simplicity. In this study, we propose a rapid, highly sensitive, and label-free pathogen assay system based on a solid-phase self-interference RPA chip (SiSA-chip) and hyperspectral interferometry. The SiSA-chips amplify and capture RPA amplicons on the chips, rather than irrelevant amplicons such as primer dimers, and the SiSA-chips are then analysed by hyperspectral interferometry. Optical length increases of SiSA-chips are used to demonstrate RPA detection results, with a limit of detection of 1.90 nm. This assay system can detect as few as six copies of the target 18S rRNA gene of Plasmodium falciparum within 20 min, with a good linear relationship between the detection results and the concentration of target genes (R2 = 0.9903). Single nucleotide polymorphism (SNP) genotyping of the dhfr gene of Plasmodium falciparum is also possible using the SiSA-chip, with as little as 1% of mutant gene distinguished from wild-type loci (m/wt). This system offers a high-efficiency (20 min), high-sensitivity (6 copies/reaction), high-specificity (1% m/wt), and low-cost (â¼1/50 of fluorescence assays for RPA) diagnosis method for pathogen DNA identification. Therefore, this system is promising for fast identification of pathogens to help diagnose infectious diseases, including SNP genotyping.
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Técnicas de Amplificação de Ácido Nucleico , Recombinases , Interferometria , Técnicas de Amplificação de Ácido Nucleico/métodos , Nucleotidiltransferases , Plasmodium falciparum/genética , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The order Oedogoniales within the single family Oedogoniaceae comprised of three genera, Oedogonium, Oedocladium, and Bulbochaete based on traditional morphological criteria. While several molecular phylogenetic studies have suggested that both Oedogonium and Oedocladium may not be monophyletic, broader taxon sampling and large amounts of molecular data acquisition could help to resolve the phylogeny and evolutionary problems of this order. This study determined five chloroplast (cp) genomes of Oedogonium species and aimed to provide further information on cp genome for a better understanding of the phylogenetic and evolutionary relationships of the order Oedogoniales. RESULTS: The five Oedogonium cp genomes showed typical quadripartite and circular structures, and were relatively conserved in their structure, gene synteny, and inverted repeats boundaries in general, except for small variation in genome sizes, AT contents, introns, and repeats. Phylogenetic analyses based on 54 cp protein-coding genes examined by maximum likelihood and Bayesian analyses using amino acid and nucleotide datasets indicated that both Oedocladium and Oedogonium are polyphyletic groups. A positively selected gene (psbA) was identified in the two Oedocladium species and the terrestrial Oedogonium species, indicating that terrestrial Oedogoniales taxa may have undergone adaptive evolution to adjust to the difference in light intensity between aquatic and terrestrial habitats. CONCLUSIONS: Our results enrich the data on cp genomes of the genus Oedogonium. The availability of these cp genomes can help in understanding the cp genome characteristics and resolve phylogenetic and evolutionary relationships of the order Oedogoniales.
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Genoma de Cloroplastos , Teorema de Bayes , Evolução Molecular , Tamanho do Genoma , Filogenia , Sequenciamento Completo do GenomaRESUMO
Single cell research with microfluidic chip is of vital importance in biomedical studies and clinical medicine. Simultaneous microfluidic cell manipulations and long-term cell monitoring needs further investigations due to the lack of label-free quantitative imaging techniques and systems. In this work, single cell capture, isolation and long-term in-situ monitoring was realized with a microfluidic cell chip, compact cell incubator and quantitative self-interference spectroscopy. The proposed imaging method could obtain quantitative and dynamic refractive index distribution in living cells. And the designed microfluidic chip could capture and isolate single cells. The customized incubator could support cell growth conditions when single cell was captured in microfluidic chip. According to the results, single cells could be trapped, transferred and pushed into the culture chamber with the microfluidic chip. The incubator could culture single cells in the chip for 120 h. The refractive index sensitivity of the proposed quantitative imaging method was 0.0282 and the relative error was merely 0.04%.
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Técnicas Analíticas Microfluídicas , Técnicas de Cultura de Células , Diagnóstico por Imagem , Microfluídica , Análise EspectralRESUMO
To investigate the molecular evolution of mitochondrial genomes among the family Odontobutidae, the complete mitochondrial genomes of Neodontobutis hainanensis and Perccottus glenii were sequenced and compared with seven odontobutids species. The genome organization, base composition, codon usage, and gene arrangement of N. hainanensis exhibited high similarity to P. glenii compared to those of other Odontobutidae species. Reconstructed phylogenetic analyses of Odontobutidae strongly supported that Neodontobutis and Perccottus formed a unifying group sister to Odontobutis. Our molecular dating time revealed that the two species diverged approximately 21.7 Ma during Miocene, later than that of Odontobutis. Selection analyses showed stronger selective constraints in mitochondrial genes for P. glenii. However, two positively selected sites in NADH4 and NADH6 genes were respectively detected in N. hainanensis and P. glenii, indicating that they might evolve different metabolic performance in response to the contrasting environments.
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Genoma Mitocondrial/genética , Perciformes/genética , Filogenia , Animais , Evolução Molecular , NAD/genética , Seleção Genética , Análise de Sequência de DNARESUMO
Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.
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High hydrostatic pressure, low temperature, and scarce food supply are the major factors that limit the survival of vertebrates in extreme deep-sea environments. Here, we constructed a high-quality genome of the deep-sea Muddy arrowtooth eel (MAE, Ilyophis brunneus, captured below a depth of 3,500 m) by using Illumina, PacBio, and Hi-C sequencing. We compare it against those of shallow-water eel and other outgroups to explore the genetic basis that underlies the adaptive evolution to deep-sea biomes. The MAE genome was estimated to be 1.47 Gb and assembled into 14 pseudo-chromosomes. Phylogenetic analyses indicated that MAE diverged from its closely related shallow-sea species, European eel, â¼111.9 Mya and experienced a rapid evolution. The genome evolutionary analyses primarily revealed the following: (i) under high hydrostatic pressure, the positively selected gene TUBGCP3 and the expanded family MLC1 may improve the cytoskeleton stability; ACOX1 may enhance the fluidity of cell membrane and maintain transport activity; the expansion of ABCC12 gene family may enhance the integrity of DNA; (ii) positively selected HARS likely maintain the transcription ability at low temperatures; and (iii) energy metabolism under a food-limited environment may be increased by expanded and positively selected genes in AMPK and mTOR signaling pathways.
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Adaptação Fisiológica , Enguias , Animais , Filogenia , Adaptação Fisiológica/genética , Enguias/genética , Citoesqueleto , Cromossomos/genéticaRESUMO
Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.
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Encefalopatias , Animais , Encefalopatias/genética , Encefalopatias/terapia , Receptor do Retrovírus Politrópico e Xenotrópico , Encéfalo/patologiaRESUMO
Lung cancer remains the most commonly diagnosed cancer and the leading cause of death from cancer. Recent research shows that the human eye can provide useful information about one's health status, but few studies have revealed that the eye's features are associated with the risk of cancer. The aims of this paper are to explore the association between scleral features and lung neoplasms and develop a non-invasive artificial intelligence (AI) method for detecting lung neoplasms based on scleral images. A novel instrument was specially developed to take the reflection-free scleral images. Then, various algorithms and different strategies were applied to find the most effective deep learning algorithm. Ultimately, the detection method based on scleral images and the multi-instance learning (MIL) model was developed to predict benign or malignant lung neoplasms. From March 2017 to January 2019, 3923 subjects were recruited for the experiment. Using the pathological diagnosis of bronchoscopy as the gold standard, 95 participants were enrolled to take scleral image screens, and 950 scleral images were fed to AI analysis. Our non-invasive AI method had an AUC of 0.897 ± 0.041(95% CI), a sensitivity of 0.836 ± 0.048 (95% CI), and a specificity of 0.828 ± 0.095 (95% CI) for distinguishing between benign and malignant lung nodules. This study suggested that scleral features such as blood vessels may be associated with lung cancer, and the non-invasive AI method based on scleral images can assist in lung neoplasm detection. This technique may hold promise for evaluating the risk of lung cancer in an asymptomatic population in areas with a shortage of medical resources and as a cost-effective adjunctive tool for LDCT screening at hospitals.
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Rapid identification of Candida species is significant for the diagnosis of vulvovaginal candidiasis (VVC). An integrated and multi-target system for the rapid, high-specificity, and high-sensitivity detection of four Candida species was developed. The system consists of a rapid sample processing cassette and a rapid nucleic acid analysis device. The cassette could process the Candida species to release nucleic acids in 15 min. The released nucleic acids were analyzed by the device as fast as within 30 min, using the loop-mediated isothermal amplification method. The four Candida species could be simultaneously identified, with each reaction using only 1.41 µL of reaction mixture, which was low cost. The RPT (rapid sample processing and testing) system could detect the four Candida species with high sensitivity (<2 CFU/reaction) and high specificity. The system also processed and analyzed 32 clinical samples, giving the results with high clinical sensitivity and specificity. Hence, the system was a significant and effective platform for the diagnosis of VVC. Furthermore, the period of validity of the reagents and chips used in the system was >90 days, and the system could also be used for the detection of bacteria.
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Candidíase Vulvovaginal , Ácidos Nucleicos , Feminino , Humanos , Candidíase Vulvovaginal/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e EspecificidadeRESUMO
The uplift of the Tibetan Plateau significantly altered the geomorphology and climate of the Euroasia by creating large mountains and rivers. Fishes are more likely to be affected relative to other organisms, as they are largely restricted to river systems. Faced with the rapidly flowing water in the Tibetan Plateau, a group of catfish has evolved greatly enlarged pectoral fins with more numbers of fin-rays to form an adhesive apparatus. However, the genetic basis of these adaptations in Tibetan catfishes remains elusive. In this study, we performed comparative genomic analyses based on the chromosome-level genome of Glyptosternum maculatum in family Sisoridae and detected some proteins with conspicuously high evolutionary rates in particular in genes involved in skeleton development, energy metabolism, and hypoxia response. We found that the hoxd12a gene evolved faster and a loss-of-function assay of hoxd12a supports a potential role for this gene in shaping the enlarged fins of these Tibetan catfishes. Other genes with amino acid replacements and signatures of positive selection included proteins involved in low temperature (TRMU) and hypoxia (VHL) responses. Functional assays reveal that the G. maculatumTRMU allele generates more mitochondrial ATP than the ancestral allele found in low-altitude fishes. Functional assays of VHL alleles suggest that the G. maculatum allele has lower transactivation activity than the low-altitude forms. These findings provide a window into the genomic underpinnings of physiological adaptations that permit G. maculatum to survive in the harsh environment of the Tibetan Himalayas that mirror those that are convergently found in other vertebrates such as humans.
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Peixes-Gato , Humanos , Animais , Peixes-Gato/genética , Tibet , Adaptação Fisiológica/genética , Aclimatação , Hipóxia/genética , AltitudeRESUMO
PURPOSE: The aim of this study is to establish a loop-mediated isothermal amplification (LAMP) method for the rapid detection of vulvovaginal candidiasis (VVC). METHODS: We developed and validated a loop-mediated isothermal amplification (LAMP) method for detecting the most common Candida species associated with VVC, including C. albicans, N. glabratus, C. tropicalis, and C. parapsilosis. We evaluated the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of the LAMP method to detect different Candida species, using the conventional culture method and internal transcribed spacer (ITS) sequencing as gold standards and smear Gram staining and real-time Rolymerase Chain Reaction (PCR) as controls. RESULTS: A total of 202 cases were enrolled, of which 88 were VVC-positive and 114 were negative. Among the 88 positive patients, the fungal culture and ITS sequencing results showed that 67 cases (76.14%) were associated with C. albicans, 13 (14.77%) with N. glabratus, 5 (5.68%) with C. tropicalis, and 3 (3.41%) with other species. Regarding the overall detection rate, the LAMP method presented sensitivity, specificity, PPV, NPV, and Kappa values of 90.91%, 100%, 100%, 93.4%, and 0.919, respectively. Moreover, the LAMP had a specificity of 100% for C. albicans, N. glabratus, and C. tropicalis, with a sensitivity of 94.03%, 100%, and 80%, respectively. Moreover, the microscopy evaluation had the highest sensitivity, while the real-time PCR was less specific for C. albicans than LAMP. In addition, CHROMagar Candida was inferior to LAMP in detecting non-albicans Candida (NAC) species. CONCLUSIONS: Based on the cost-effective, rapid, and inexpensive characteristics of LAMP, coupled with the high sensitivity and specificity of our VVC-associated Candida detection method, we provided a possibility for the point-of-care testing (POCT) of VVC, especially in developing countries and some laboratories with limited resources.
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Harsh environments provide opportunities to study how different species adapt, at the molecular level, to similar environmental stressors. High hydrostatic pressure, low temperature, and absence of sunlight in the deep-sea environment are challenging conditions for gene expression, cell morphology and vision. Adaptation of fish to this environment appears independently in at least 22 orders of fish, but it remains uncertain whether these adaptations represent convergent evolution. In this study, we performed comparative genomic analysis of 80 fish species to determine genetic evidences for adaptations to the deep-sea environment. The 80 fishes were divided into six groups according to their order. Positive selection and convergent evolutionary analysis were performed and functional enrichment analysis of candidate genes was performed. Positively selected genes (pik3ca, pik3cg, vcl and sphk2) were identified to be associated with the cytoskeletal response to mechanical forces and gene expression. Consistent signs of molecular convergence genes (grk1, ednrb, and nox1) in dark vision, skin color, and bone rarefaction were revealed. Functional assays of Grk1 showed that the convergent sites improved dark vision in deep-sea fish. By identifying candidate genes and functional profiles potentially involved in cold, dark, and high-pressure responses, the results of this study further enrich the understanding of fish adaptations to deep-sea environments.