MutS is a key component of the mismatch repair (MMR) pathway. Members of the MutS protein family are present in prokaryotes, eukaryotes, and viruses. Six MutS homologs (MSH1–6) have been identified in yeast, of which three function in nuclear MMR, while MSH1 functions in mitochondrial DNA repair. MSH proteins are believed to be well conserved in animals, except for MSH1—which is thought to be lost. Two intriguing exceptions to this general picture have been found, both in the class Anthozoa within the phylum Cnidaria. First, an ortholog of the yeast-MSH1 was reported in one hexacoral species. Second, a MutS homolog (mtMutS) has been found in the mitochondrial genome of all octocorals. To understand the origin and potential functional implications of these exceptions, we investigated the evolution of the MutS family both in Cnidaria and in animals in general. Our study confirmed the acquisition of octocoral mtMutS by horizontal gene transfer from a giant virus. Surprisingly, we identified MSH1 in all hexacorals and several sponges and placozoans. By contrast, MSH1 orthologs were lacking in other cnidarians, ctenophores, and bilaterian animals. Furthermore, while we identified MSH2 and MSH6 in nearly all animals, MSH4, MSH5, and, especially, MSH3 were missing in multiple species. Overall, our analysis revealed a dynamic evolution of the MutS family in animals, with multiple losses of MSH1, MSH3, some losses of MSH4 and MSH5, and a gain of the octocoral mtMutS. We propose that octocoral mtMutS functionally replaced MSH1 that was present in the common ancestor of Anthozoa.

中文翻译：

---

动物中 MSH1 的多重丢失、mtMutS 的增加以及 DNA 修复蛋白 MutS 家族的其他变化


MutS 是错配修复 (MMR) 途径的关键组成部分。 MutS 蛋白家族的成员存在于原核生物、真核生物和病毒中。在酵母中已鉴定出 6 个 MutS 同源物 (MSH1-6)，其中 3 个在核 MMR 中发挥作用，而 MSH1 在线粒体 DNA 修复中发挥作用。 MSH 蛋白被认为在动物体内保存完好，但 MSH1 除外，MSH1 被认为已丢失。人们在这一总体情况中发现了两个有趣的例外，它们都属于刺胞动物门的珊瑚虫纲。首先，在一种六珊瑚物种中报道了酵母 MSH1 的直系同源物。其次，在所有八珊瑚的线粒体基因组中都发现了 MutS 同源物 (mtMutS)。为了了解这些异常的起源和潜在的功能影响，我们研究了刺胞动物和一般动物中 MutS 家族的进化。我们的研究证实了通过水平基因转移从巨型病毒获得八珊瑚mtMutS。令人惊讶的是，我们在所有六珊瑚以及一些海绵和长生动物中都发现了 MSH1。相比之下，其他刺胞动物、栉水母动物和两侧对称动物中缺乏 MSH1 直系同源物。此外，虽然我们在几乎所有动物中都鉴定出了 MSH2 和 MSH6，但 MSH4、MSH5，尤其是 MSH3 在多个物种中缺失。总体而言，我们的分析揭示了动物中 MutS 家族的动态进化，其中 MSH1、MSH3 多次丢失，MSH4 和 MSH5 部分丢失，以及八珊瑚 mtMutS 的增加。我们认为八珊瑚 mtMutS 在功能上取代了 Anthozoa 共同祖先中存在的 MSH1。