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 ar...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.maculatum TRMU 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.展开更多
Signal transducer and activator of transcription 5b(STAT5b) has been identified as a key downstream mediator of growth hormone(GH) signaling in somatic growth of mammalian. However, the corresponding homologue gen...Signal transducer and activator of transcription 5b(STAT5b) has been identified as a key downstream mediator of growth hormone(GH) signaling in somatic growth of mammalian. However, the corresponding homologue gene of Stat5b is unknown in fish species. In this study, we generated loss-offunction mutants in stat5.1 and stat5.2, two stat5 homologues existing in zebrafish. In stat5.1-deficient zebrafish, a significant reduction of body length and body weight was detected in the embryos/larvae and adults compared with the wild-type control fish, and sexual size dimorphism in adult zebrafish was also eliminated. However, the stat5.2-deficient zebrafish displayed a normal developmental phenotype during all lifespan. Chromatin immunoprecipitation combined with deep sequencing(Ch IP-seq) method was adopted to further investigate the potential transcriptional targets of Stat5 protein and cast much light upon the biological function of Stat5. We identified more than 800 genes as transcriptional targets of Stat5 during zebrafish embryogenesis. KEGG analysis indicated that the Stat5 target gene network is predominantly linked to the metabolic pathways, neuroactive ligand-receptor interaction and JAK-STAT signaling pathways. Further validation studies suggested that Stat5.1 protein could directly regulate the expression of gh1, and stat5.1-mutated zebrafish showed a reduction of gh1 mRNA level. In the present study, stat5.1 was revealed as the corresponding homologue gene of Stat5b in fish species. Additionally,we found a novel molecular interaction between Stat5.1/Stat5b and GH, and unraveled a positive feedback loop Stat5.1-GH-Stat5.1 which is necessary for somatic growth and body development in zebrafish.展开更多
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(XDB31000000)the National Natural Science Foundation of China(32170480,31972866,31702016,31601858,32022009)+5 种基金Chinese Academy of Sciences(Youth Innovation Promotion Association),Chinese Academy of Sciences(http://www.yicas.cn)the Pioneer Hundred Talents Program,and ZDBS-LYSM005)the Second Tibetan Plateau Scientific Expedition and Research Program(STEP,2019QZKK0501)State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences(GREKF21-04)the Young Top-notch Talent Cultivation Program of Hubei Provincesupported by the Wuhan Branch,Supercomputing Center,Chinese Academy of Sciences,China。
文摘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.maculatum TRMU 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.
基金supported by the Fundamental Research Funds for the Central Universities(2662017PY013 and 2662015PY101)the Autonomous Project of State Key Laboratory of Freshwater Ecology and Biotechnology(2011FBZ22)the Autonomous Projects of the Institute of Hydrobiology,Chinese Academy of Sciences(Y25A17 and Y45A171301)
文摘Signal transducer and activator of transcription 5b(STAT5b) has been identified as a key downstream mediator of growth hormone(GH) signaling in somatic growth of mammalian. However, the corresponding homologue gene of Stat5b is unknown in fish species. In this study, we generated loss-offunction mutants in stat5.1 and stat5.2, two stat5 homologues existing in zebrafish. In stat5.1-deficient zebrafish, a significant reduction of body length and body weight was detected in the embryos/larvae and adults compared with the wild-type control fish, and sexual size dimorphism in adult zebrafish was also eliminated. However, the stat5.2-deficient zebrafish displayed a normal developmental phenotype during all lifespan. Chromatin immunoprecipitation combined with deep sequencing(Ch IP-seq) method was adopted to further investigate the potential transcriptional targets of Stat5 protein and cast much light upon the biological function of Stat5. We identified more than 800 genes as transcriptional targets of Stat5 during zebrafish embryogenesis. KEGG analysis indicated that the Stat5 target gene network is predominantly linked to the metabolic pathways, neuroactive ligand-receptor interaction and JAK-STAT signaling pathways. Further validation studies suggested that Stat5.1 protein could directly regulate the expression of gh1, and stat5.1-mutated zebrafish showed a reduction of gh1 mRNA level. In the present study, stat5.1 was revealed as the corresponding homologue gene of Stat5b in fish species. Additionally,we found a novel molecular interaction between Stat5.1/Stat5b and GH, and unraveled a positive feedback loop Stat5.1-GH-Stat5.1 which is necessary for somatic growth and body development in zebrafish.