Origins, genomic structure and copy number variation of snake venom myotoxins
Origins, genomic structure and copy number variation of snake venom myotoxins
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DOI：
10.1016/j.toxicon.2022.06.014
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发表时间：
2022-07-12
期刊：
影响因子：
2.8
通讯作者：
Castoe, Todd A.
中科院分区：
文献类型：
--
作者：
Gopalan, Siddharth S.;Perry, Blair W.;Castoe, Todd A.
巴豆胺，肌毒素a和同系物是短肽，通常构成响尾蛇毒液的主要部分，并已被广泛研究其生物活性。这些毒素被认为是重要的快速固定哺乳动物猎物，并牵连在严重的，有时是致命的，对人类的毒液蛰入的反应。虽然可以获得多种毒蛇的高质量参考基因组，但编码肌毒素的基因座尚未在任何现有的基因组组装中成功组装。在这里，我们整合新的和现有的基因组和转录组数据从草原响尾蛇（响尾蛇viridis viridis）重建，表征和推断肌肉毒素编码基因座的染色体位置。我们整合了长读转录组学（Pacific Bioscience的Iso-Seq）和短读RNA-seq，以推断基因序列多样性并表征多种组织中肌毒素和旁系同源β-防御素表达的模式。我们还确定了两个长的非编码RNA序列都编码功能性肌毒素，证明了一个新发现的来源毒液编码序列的多样性。我们还整合了长距离配对染色质接触数据和连接阅读测序，以推断三个肌毒素样基因座的结构和染色体位置。此外，我们的结论是，毒液相关的肌肉毒素位于1号染色体上，是相邻的非毒液旁系同源物。与这个位点的毒液成分，我们发现的证据表明，该基因的启动子是选择性开放的毒液腺组织，并包含广泛的反式调节途径，调节蛇毒涉及的转录因子结合位点。这项研究提供了迄今为止最好的肌毒素基因座基因组重建，并提出了有关肌毒素与相关基因之间的生理作用和相互作用以及蛇毒变异的基因组起源的问题。
Crotamine, myotoxin a and homologs are short peptides that often comprise major fractions of rattlesnake venoms and have been extensively studied for their bioactive properties. These toxins are thought to be important for rapidly immobilizing mammalian prey and are implicated in serious, and sometimes fatal, re-sponses to envenomation in humans. While high quality reference genomes for multiple venomous snakes are available, the loci that encode myotoxins have not been successfully assembled in any existing genome assembly. Here, we integrate new and existing genomic and transcriptomic data from the Prairie Rattlesnake (Crotalus viridis viridis) to reconstruct, characterize, and infer the chromosomal locations of myotoxin-encoding loci. We integrate long-read transcriptomics (Pacific Bioscience's Iso-Seq) and short-read RNA-seq to infer gene sequence diversity and characterize patterns of myotoxin and paralogous beta-defensin expression across multiple tissues. We also identify two long non-coding RNA sequences which both encode functional myotoxins, demonstrating a newly discovered source of venom coding sequence diversity. We also integrate long-range mate-pair chromatin contact data and linked-read sequencing to infer the structure and chromosomal locations of the three myotoxin-like loci. Further, we conclude that the venom-associated myotoxin is located on chromosome 1 and is adjacent to non-venom paralogs. Consistent with this locus contributing to venom composition, we find evidence that the promoter of this gene is selectively open in venom gland tissue and contains transcription factor binding sites implicated in broad trans-regulatory pathways that regulate snake venoms. This study provides the best genomic reconstruction of myotoxin loci to date and raises questions about the physiological roles and interplay between myotoxin and related genes, as well as the genomic origins of snake venom variation.