Soft-bodied slow-moving sea creatures such as sea stars and sea cucumbers lack an adaptive immune system and have instead evolved the ability to make specialized protective chemicals (glycosylated steroids and triterpenes) as part of their innate immune system. This raises the intriguing question of how these biosynthetic pathways have evolved. Sea star saponins are steroidal, while those of the sea cucumber are triterpenoid. Sterol biosynthesis in animals involves cyclization of 2,3-oxidosqualene to lanosterol by the oxidosqualene cyclase (OSC) enzyme lanosterol synthase (LSS). Here we show that sea cucumbers lack LSS and instead have two divergent OSCs that produce triterpene saponins and that are likely to have evolved from an ancestral LSS by gene duplication and neofunctionalization. We further show that sea cucumbers make alternate sterols that confer protection against self-poisoning by their own saponins. Collectively, these events have enabled sea cucumbers to evolve the ability to produce saponins and saponin-resistant sterols concomitantly.

海星和海参等身体柔软、行动缓慢的海洋生物缺乏适应性免疫系统，而是进化出了制造特殊保护性化学物质（糖基化类固醇和三萜类化合物）的能力，作为其先天免疫系统的一部分。这就提出了一个有趣的问题，即这些生物合成途径是如何进化的。海星皂苷属于甾体，而海参皂苷属于三萜类。动物中的甾醇生物合成涉及通过氧化角鲨烯环化酶 (OSC) 羊毛甾醇合酶 (LSS) 将 2,3-氧化角鲨烯环化为羊毛甾醇。在这里，我们表明海参缺乏 LSS，而是有两个不同的 OSC，它们产生三萜皂苷，并且很可能是通过基因复制和新功能化从祖先的 LSS 进化而来的。我们进一步表明，海参会产生替代甾醇，这些甾醇可以防止它们自己的皂甙导致自身中毒。总的来说，这些事件使海参进化出同时产生皂苷和皂苷抗性甾醇的能力。