Naturalis Biodiversity Center, 2333 CR, Leiden, The Netherlands.
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20651-6. doi: 10.1073/pnas.1314702110. Epub 2013 Dec 2.
Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection.
蛇是无肢的掠食者，许多物种利用毒液来帮助制服相对较大、灵活的猎物。蛇毒是由几个多基因家族编码的复杂蛋白质混合物，它们协同作用导致猎物丧失能力。为了研究毒液的进化，我们对一种毒蛇——眼镜王蛇（Ophiophagus hannah）的基因组进行了测序和分析，并将其与我们从该物种获得的独特转录组、microRNA 和蛋白质组数据集，以及其他脊椎动物的数据进行了比较。与鸭嘴兽（唯一具有测序基因组的其他有毒脊椎动物）不同，我们发现蛇毒素基因通过几种不同的共适应机制进化，并表现出惊人的基因重复和定向选择水平的变化，这与它们在猎物捕获中的功能重要性相关。神秘的附属毒液腺与主毒液腺的毒素基因表达模式非常不同，似乎多次招募毒素样凝集素基因用于新的非毒性功能。此外，组织特异性 microRNA 分析表明，毒液分泌系统的核心遗传调控成分可能是从胰腺起源共适应的。尽管眼镜王蛇没有四肢，但我们从蛇毒腺中恢复了所有参与羊膜动物肢体发育的 Hox 基因的编码序列，除了 Hoxd12 基因。我们的研究结果提供了一个独特的视角，了解蛇毒的起源和进化，并揭示了在这种复杂的生物武器系统中对自然选择的多种基因组水平适应性反应。更广泛地说，它们为在强烈选择压力下蛋白质进化的机制提供了深入的了解。
