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The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins
Nature Genetics ( IF 30.8 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41588-019-0559-8
Kushal Suryamohan 1, 2 , Sajesh P Krishnankutty 3, 4 , Joseph Guillory 1 , Matthew Jevit 5 , Markus S Schröder 1 , Meng Wu 1 , Boney Kuriakose 3 , Oommen K Mathew 3 , Rajadurai C Perumal 3 , Ivan Koludarov 6 , Leonard D Goldstein 1, 7 , Kate Senger 1 , Mandumpala Davis Dixon 3 , Dinesh Velayutham 3 , Derek Vargas 1, 2 , Subhra Chaudhuri 1 , Megha Muraleedharan 3 , Ridhi Goel 3 , Ying-Jiun J Chen 1 , Aakrosh Ratan 8 , Peter Liu 9 , Brendan Faherty 9 , Guillermo de la Rosa 10 , Hiroki Shibata 11 , Miriam Baca 12 , Meredith Sagolla 12 , James Ziai 12 , Gus A Wright 13 , Domagoj Vucic 14 , Sangeetha Mohan 15 , Aju Antony 15 , Jeremy Stinson 1 , Donald S Kirkpatrick 9 , Rami N Hannoush 14 , Steffen Durinck 1, 7 , Zora Modrusan 1 , Eric W Stawiski 1, 2 , Kristen Wiley 16 , Terje Raudsepp 5 , R Manjunatha Kini 17 , Arun Zachariah 4, 18 , Somasekar Seshagiri 1, 4
Affiliation  

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the ‘venom-ome’ and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 ‘venom-ome-specific toxins’ (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery.



中文翻译:

印度眼镜蛇参考基因组和转录组能够全面鉴定毒液毒素

毒蛇咬伤是一种严重且被忽视的热带疾病,每年造成约 100,000 人死亡。对毒素基因进行高质量、基于基因组的综合表征将有助于开发有效的人源化重组抗蛇毒血清。我们报告了眼镜蛇眼镜蛇的从头近染色体基因组组装,印度眼镜蛇,一种剧毒,医学上重要的蛇。我们的组装有一个 223.35 Mb 的支架 N50,其中 19 个支架包含 95% 的基因组。在预测的 23,248 个蛋白质编码基因中,12,346 个毒腺表达基因构成了“毒液组”,其中包括来自 33 个毒素家族的 139 个基因。在 139 个毒素基因中,有 19 个“毒液组特异性毒素”(VSTs)显示出毒液腺特异性表达,这些可能编码最小的核心毒液效应蛋白。通过重组 VST 表达重组的合成毒液将有助于快速开发安全有效的合成抗蛇毒血清。此外,我们的基因组可以作为蛇基因组的参考,支持进化研究并实现毒液驱动的药物发现。

更新日期:2020-01-06
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