Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins.
10.1016/j.apsb.2022.11.015
- Author:
Jiang XU
1
;
Shuai GUO
1
;
Xianmei YIN
1
;
Mingqian LI
2
;
He SU
3
;
Xuejiao LIAO
4
;
Qiushi LI
5
;
Liang LE
5
;
Shiyu CHEN
1
;
Baosheng LIAO
3
;
Haoyu HU
5
;
Juan LEI
5
;
Yingjie ZHU
6
;
Xiaohui QIU
3
;
Lu LUO
5
;
Jun CHEN
7
;
Ruiyang CHENG
5
;
Zhenzhan CHANG
8
;
Han ZHANG
9
;
Nicholas Chieh WU
10
;
Yiming GUO
11
;
Dianyun HOU
12
;
Jin PEI
1
;
Jihai GAO
1
;
Yan HUA
13
;
Zhihai HUANG
3
;
Shilin CHEN
1
Author Information
1. Institute of Herbgenomics, State Key Laboratory of Southwest Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
2. Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
3. 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 510006, China.
4. Pharmacy College, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
5. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
6. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7. Beijing Engineering Research Center of Pediatric Surgery, Engineering and Transformation Center, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing 100045, China.
8. School of Basic Medical Sciences, Peking University, Beijing 100191, China.
9. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
10. School of Life and Environmental Sciences, the University of Sydney, NSW, 2006, Australia.
11. University of Pittsburgh, Kenneth P. Dietrich School of Arts and Sciences, Pittsburgh, PA 15260, USA.
12. Agricultural College, Henan University of Science and Technology, Luoyang 471000, China.
13. Guangdong Provincial Key Laboratory of Silviculture, Protection and Utilization, Guangdong Academy of Forestry, Guangzhou 510520, China.
- Publication Type:Journal Article
- Keywords:
Antivenoms;
Chromatin;
Gene regulation;
Medicinal snake;
Neurotoxin origin
- From:
Acta Pharmaceutica Sinica B
2023;13(5):2234-2249
- CountryChina
- Language:English
-
Abstract:
The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, 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 genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.
