Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable models for evolutionary developmental biology.The dragon-eye strain is characterized by protrud...Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable models for evolutionary developmental biology.The dragon-eye strain is characterized by protruding eyes(analogous to those of Chinese dragons).Although the strain has been selected for about 400 years,the mechanism of its eye development remains unclear.In this study,a stable dragon-eye goldfish strain with a clear genetic background was rapidly established and studied.We found that upregulation of the PPAR signaling pathway accompanied by an increase in lipid accumulation might trigger the morphological and structural transformation of the eye in dragon-eye goldfish.At the developmental stage of proptosis(eye protrusion),downregulation of the phototransduction pathway was consistent with the structural defects and myopia of the dragon-eye strain.With the impairment of retinal development,cytokine-induced inflammation was activated,especially after proptosis,similar to the pathologic symptoms of many human ocular diseases.In addition,differentially expressed transcription factors were significantly enriched in the PAX and homeobox families,two well-known transcription factor families involved in eye development.Therefore,our findings reveal the dynamic changes in key pathways during eye development in dragon-eye goldfish,and provide insights into the molecular mechanisms underlying drastically altered eyes in goldfish and human ocular disease.展开更多
Goldfish(Carassius auratus) have long fascinated evolutionary biologists and geneticists because of their diverse morphological and color variations.Recent genome-wide association studies have provided a clue to uncov...Goldfish(Carassius auratus) have long fascinated evolutionary biologists and geneticists because of their diverse morphological and color variations.Recent genome-wide association studies have provided a clue to uncover genomic basis underlying these phenotypic variations,but the causality between phenotypic and genotypic variations have not yet been confirmed.Here,we edited proposed candidate genes to recreate phenotypic traits and developed a rapid biotechnology approach which combines gene editing with high-efficiency breeding,artificial gynogenesis,and temperature-induced sex reversal to establish homozygous mutants within two generations(approximately eight months).We first verified that low-density lipoprotein receptorrelated protein 2B(lrp2a B) is the causal gene for the dragon-eye variation and recreated the dragon-eye phenotype in side-view Pleated-skirt Lion-head goldfish.Subsequently,we demonstrated that the albino phenotype was determined by both homeologs of oculocutaneous albinism type II(oca2),which has subfunctionalized to differentially govern melanogenesis in the goldfish body surface and pupils.Overall,we determined two causal genes for dragon-eye and albino phenotypes,and created four stable homozygous strains and more appealing goldfish with desirable traits.The developed biotechnology approach facilitates precise genetic breeding,which will accelerate re-domestication and recreation of phenotypically desirable goldfish.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(31930111)+2 种基金the China Agriculture Research System(CARS-45-07)the Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology(2019FBZ04)supported by the Wuhan Branch,Supercomputing Centre,Chinese Academy of Sciences,China。
文摘Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable models for evolutionary developmental biology.The dragon-eye strain is characterized by protruding eyes(analogous to those of Chinese dragons).Although the strain has been selected for about 400 years,the mechanism of its eye development remains unclear.In this study,a stable dragon-eye goldfish strain with a clear genetic background was rapidly established and studied.We found that upregulation of the PPAR signaling pathway accompanied by an increase in lipid accumulation might trigger the morphological and structural transformation of the eye in dragon-eye goldfish.At the developmental stage of proptosis(eye protrusion),downregulation of the phototransduction pathway was consistent with the structural defects and myopia of the dragon-eye strain.With the impairment of retinal development,cytokine-induced inflammation was activated,especially after proptosis,similar to the pathologic symptoms of many human ocular diseases.In addition,differentially expressed transcription factors were significantly enriched in the PAX and homeobox families,two well-known transcription factor families involved in eye development.Therefore,our findings reveal the dynamic changes in key pathways during eye development in dragon-eye goldfish,and provide insights into the molecular mechanisms underlying drastically altered eyes in goldfish and human ocular disease.
基金supported by the National Key Research and Development Program of China(2018YFD0901202)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB31000000)+3 种基金the Knowledge Innovation Program of Wuhan-Basic Research(2022020801010143)the Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology(2021FB02)the China Agriculture Research System of MOF and MARAsupported by the Wuhan Branch,Supercomputing Center,Chinese Academy of Sciences,China。
文摘Goldfish(Carassius auratus) have long fascinated evolutionary biologists and geneticists because of their diverse morphological and color variations.Recent genome-wide association studies have provided a clue to uncover genomic basis underlying these phenotypic variations,but the causality between phenotypic and genotypic variations have not yet been confirmed.Here,we edited proposed candidate genes to recreate phenotypic traits and developed a rapid biotechnology approach which combines gene editing with high-efficiency breeding,artificial gynogenesis,and temperature-induced sex reversal to establish homozygous mutants within two generations(approximately eight months).We first verified that low-density lipoprotein receptorrelated protein 2B(lrp2a B) is the causal gene for the dragon-eye variation and recreated the dragon-eye phenotype in side-view Pleated-skirt Lion-head goldfish.Subsequently,we demonstrated that the albino phenotype was determined by both homeologs of oculocutaneous albinism type II(oca2),which has subfunctionalized to differentially govern melanogenesis in the goldfish body surface and pupils.Overall,we determined two causal genes for dragon-eye and albino phenotypes,and created four stable homozygous strains and more appealing goldfish with desirable traits.The developed biotechnology approach facilitates precise genetic breeding,which will accelerate re-domestication and recreation of phenotypically desirable goldfish.
