Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.
Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.
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DOI：
10.1186/1471-2164-15-366
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发表时间：
2014-06-11
期刊：
影响因子：
4.4
通讯作者：
Garb JE
中科院分区：
文献类型：
--
作者：
Haney RA;Ayoub NA;Clarke TH;Hayashi CY;Garb JE
动物毒液因其在药理发现和了解天然化学进化方面的潜力而吸引了人们的极大兴趣。下一代转录组学和蛋白质组学为毒液表征提供了无与伦比但未得到充分利用的能力。我们将多组织RNA-Seq与质谱学和生物信息学分析相结合，对西部黑寡妇蜘蛛(Latrodectus Heperus)的毒腺特异性转录本和毒液蛋白进行了分析，并对其进化进行了研究。我们估计了97,217个 L.Hesperus转录本在毒腺中的表达，而不是丝绸和头胸组织。我们鉴定了695个毒腺特异性转录本(VST)，其中许多BLAST和GO术语分析表明可能作为毒素或其递送媒介发挥作用。约38%的VST具有BLAST，包括乳杆菌毒素、抑制物胱氨酸结毒素、薯片、透明质酸酶、几丁质酶和蛋白酶，59%的VST具有预测的蛋白质结构域。乳杆菌毒素是一种毒素，可导致脊椎动物或无脊椎动物神经元释放大量神经递质。我们发现 ≥ 20不同的乳杆菌毒素类似物在橙子毒腺中表达，显著增加了这个具有重要生物医学意义的家族。橙皮蛇毒的质谱学鉴定出49种VST蛋白，其中24种是毒素。系统发育分析表明，毒腺特异基因家族的扩张和组织表达的变化。比较多个组织的定量表达分析对于鉴定毒腺特异性转录本是必要的。我们呈现了一个黑寡妇毒液特定的外显子组，它揭示了一个不同的毒素和相关蛋白的宝库，暗示了一个动态的进化史。鉴于新出现的复杂性，有理由重新评估黑寡妇毒液的功能活性。本文的在线版本(DOI：10.1186/1471-2164-15-366)包含补充材料，授权用户可以使用。
Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution. We estimated expression of 97,217 L. hesperus transcripts in venom glands relative to silk and cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs), many of which BLAST and GO term analyses indicate may function as toxins or their delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of VSTs had predicted protein domains. Latrotoxins are venom toxins that cause massive neurotransmitter release from vertebrate or invertebrate neurons. We discovered ≥ 20 divergent latrotoxin paralogs expressed in L. hesperus venom glands, significantly increasing this biomedically important family. Mass spectrometry of L. hesperus venom identified 49 proteins from VSTs, 24 of which BLAST to toxins. Phylogenetic analyses showed venom gland specific gene family expansions and shifts in tissue expression. Quantitative expression analyses comparing multiple tissues are necessary to identify venom gland specific transcripts. We present a black widow venom specific exome that uncovers a trove of diverse toxins and associated proteins, suggesting a dynamic evolutionary history. This justifies a reevaluation of the functional activities of black widow venom in light of its emerging complexity. The online version of this article (doi:10.1186/1471-2164-15-366) contains supplementary material, which is available to authorized users.
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影响因子：
5.6
作者：
Kaplan, Noarn;Morpurgo, Noa;Linial, Michal
通讯作者：
Linial, Michal
影响因子：
4.8
作者：
Dulubova, IE;Krasnoperov, VG;Usherwood, PNR
通讯作者：
Usherwood, PNR
DOI：
10.1093/bioinformatics/btp348
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Capella-Gutiérrez S;Silla-Martínez JM;Gabaldón T
通讯作者：
Gabaldón T
影响因子：
5.8
作者：
Graudins, Andis;Little, Michelle J.;Nicholson, Graham M.
通讯作者：
Nicholson, Graham M.
影响因子：
56.9
作者：
FINKELSTEIN, A;RUBIN, LL;TZENG, MC
通讯作者：
TZENG, MC