文献类型： 外文期刊

作者： Zhang, Dong ¹ ; Zhao, Jie-Mei ¹ ; Xiang, Chuan-Yu ¹ ; Ma, Yi-Wen ¹ ; Lei, Hong-Peng ⁴ ; Shi, Yu-Ying ¹ ; Zhou, Shun ⁶ ; Zeng, Xiaofei ⁵ ; Chen, Jinsong ⁷ ; Liu, Fei ³ ; Zeng, Benhe ⁹ ; Song, Rui ¹⁰ ; Hu, Ye ¹ ; Zhang, Feng ¹ ; Liu, Xiang ¹ ; Li, Wen-Xiang ¹² ; Wang, Gui-Tang ¹² ; Jakovlic, Ivan ¹ ;

作者机构： 1.Lanzhou Univ, State Key Lab Herbage Improvement & Grassland Agro, Lanzhou 730000, Gansu, Peoples R China

2.Lanzhou Univ, Coll Ecol, Lanzhou 730000, Gansu, Peoples R China

3.Xizang Univ, Sch Ecol & Environm, Key Lab Biodivers & Environm Qinghai Tibetan Plate, Minist Educ, Lhasa 850000, Xizang, Peoples R China

4.Shenyang Municipal Bur Ecol & Environm, Shenyang 110167, Liaoning, Peoples R China

5.Chinese Acad Agr Sci, Guangdong Lab Lingnan Modern Agr,Genome Anal Lab, Agr Genom Inst Shenzhen,Minist Agr & Rural Affairs, Shenzhen Branch,State Key Lab Trop Crop Breeding, Shenzhen 518120, Guangdong, Peoples R China

6.Chinese Acad Fishery Sci, Yangtze River Fisheries Res Inst, Wuhan 430223, Hubei, Peoples R China

7.Sun Yat Sen Univ, State Key Lab Biocontrol, Guangzhou 510275, Peoples R China

8.Sun Yat Sen Univ, Sch Life Sci, Southern Marine Sci & Engn Guangdong Lab Zhuhai, Guangdong Prov Key Lab Aquat Econ Anim, Guangzhou 510275, Peoples R China

9.Xizang Acad Agr & Anim Husb Sci, Inst Fisheries Sci, Lhasa 850032, Xizang, Peoples R China

10.Hunan Fisheries Res Inst, Changsha 410153, Hunan, Peoples R China

11.Aquat Prod Seed Stock Stn, Changsha 410153, Hunan, Peoples R China

12.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Breeding Biotechnol & Sustainable Aq, Wuhan 430072, Peoples R China

关键词： antagonistic coevolution; cAMP signaling; GPCRs; immune coadaptation; innexins; interactome; PRKACB

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

ISSN：

年卷期： 2025 年

页码：

收录情况： SCI

摘要： The host-parasite arms race involves complex molecular crosstalk mediated by protein-protein interactions (PPIs). Bioinformatic analyses can be used to predict both host-parasite PPIs and potential drug targets in parasite genomes, but high-quality genomic data remain scarce for parasitic monogenean flatworms. Herein, an experimental lineage of Gyrodactylus kobayashii (Monopisthocotylea: Gyrodactylidae) is set up on goldfish hosts and used to conduct phased genome assembly using long-range PacBio HiFi and Hi-C technologies. In silico analyses of genomes of three Gyrodactylus species identified innexins as the most promising novel drug candidate genes. Drug screening and experimental verification singled out Imatinib as the most promising drug targeting innexins, with a high efficiency against G. kobayashii (100% mortality at 25 mu M within 6 h in vitro) and low toxicity to the host. Prediction of PPIs in three Gyrodactylus-host pairs revealed proteins associated with cAMP-dependent signaling as key candidates, including the host's PRKACB and the parasite's PRKAR2A, RAP1A, ULK2, and Catenin Beta-2. Two interacting G proteins are also identified: GNAO1 and GNB5. As the first high-quality phased chromosome-level genomic assembly for "monogeneans" and the first identification of PPIs in a fish-parasite system, this study significantly advances the understanding of host-parasite interactions at the genomic level.