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Genomic,transcriptomic,and epigenomic analysis of a medicinal snake,Bungarus multicinctus,to provides insights into the origin of Elapidae neurotoxins

引用

Acta Pharmaceutica Sinica B 2023年第5期13卷 2234-2249页

作者： Jiang Xu Shuai Guo Xianmei Yin Mingqian Li He Su Xuejiao Liao Qiushi Li Liang Le Shiyu Chen Baosheng Liao Haoyu Hu Juan Lei Yingjie Zhu Xiaohui Qiu Lu Luo Jun Chen Ruiyang Cheng Zhenzhan Chang Han Zhang Nicholas Chieh Wu Yiming Guo Dianyun Hou Jin Pei Jihai Gao Yan Hua Zhihai Huang Shilin Chen Institute of Herbgenomics State Key Laboratory of Southwest Chinese Medicine ResourcesPharmacy CollegeChengdu University of Traditional Chinese MedicineChengdu 611137China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province Zhejiang Academy of Traditional Chinese MedicineTongde Hospital of Zhejiang ProvinceHangzhou 310012China Guangdong Provincial Hospital of Chinese Medicine(the Second Clinical Medical College of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Traditional Chinese Medicine)Guangzhou 510006China Pharmacy College Shandong University of Traditional Chinese MedicineJinan 250355China Department of Pathology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Beijing Engineering Research Center of Pediatric Surgery Engineering and Transformation CenterBeijing Children's HospitalNational Center for Children's HealthCapital Medical UniversityBeijing 100045China School of Basic Medical Sciences Peking UniversityBeijing 100191China School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 300193China School of Life and Environmental Sciences the University of SydneyNSW2006Australia University of Pittsburgh Kenneth P.Dietrich School of Arts and SciencesPittsburghPA 15260USA Agricultural College Henan University of Science and TechnologyLuoyang 471000China Guangdong Provincial Key Laboratory of Silviculture Protection and UtilizationGuangdong Academy of ForestryGuangzhou 510520China

The many-banded krait,Bungarus multicinctus,has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese *** of its venoms classified chief phyla of modern animal ***,the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality ***,we present the 1.58 Gbp genome of *** assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 *** bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local *** truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins(3FTxs)from membrane tethering before the Colubroidea *** expansion and mutations diversified and recruited these *** the cobra/krait divergence,the modern unit-B ofβ-bungarotoxin emerged with an extra cysteine residue.A subsequent point substitution in unit-A enabled theβ-bungarotoxin covalent *** *** gene expression,chromatin topological organization,and histone modification characteristics were featured by transcriptome,proteome,chromatin conformation capture sequencing,and *** results highlighted that venom production was under a sophisticated *** findings provide new insights into snake neurotoxin research,meanwhile will facilitate antivenom development,toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

关键词： Medicinal snake neurotoxin origin Antivenoms Gene regulation Chromatin

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