Department of Zoology, University of Innsbruck, Austria.
Metallomics. 2020 May 27;12(5):702-720. doi: 10.1039/c9mt00259f.
The tiny contribution of cadmium (Cd) to the composition of the earth's crust contrasts with its high biological significance, owing mainly to the competition of Cd with the essential zinc (Zn) for suitable metal binding sites in proteins. In this context it was speculated that in several animal lineages, the protein family of metallothioneins (MTs) has evolved to specifically detoxify Cd. Although the multi-functionality and heterometallic composition of MTs in most animal species does not support such an assumption, there are some exceptions to this role, particularly in animal lineages at the roots of animal evolution. In order to substantiate this hypothesis and to further understand MT evolution, we have studied MTs of different snails that exhibit clear Cd-binding preferences in a lineage-specific manner. By applying a metallomics approach including 74 MT sequences from 47 gastropod species, and by combining phylogenomic methods with molecular, biochemical, and spectroscopic techniques, we show that Cd selectivity of snail MTs has resulted from convergent evolution of metal-binding domains that significantly differ in their primary structure. We also demonstrate how their Cd selectivity and specificity has been optimized by the persistent impact of Cd through 430 million years of MT evolution, modifying them upon lineage-specific adaptation of snails to different habitats. Overall, our results support the role of Cd for MT evolution in snails, and provide an interesting example of a vestigial abiotic factor directly driving gene evolution. Finally, we discuss the potential implications of our findings for studies devoted to the understanding of mechanisms leading to metal specificity in proteins, which is important when designing metal-selective peptides.
镉 (Cd) 在地球地壳组成中的微小贡献与其重要的生物学意义形成鲜明对比，这主要归因于 Cd 与必需的锌 (Zn) 对蛋白质中合适金属结合位点的竞争。在这种情况下，有人推测，在几个动物谱系中，金属硫蛋白 (MT) 蛋白家族已经进化为专门解毒 Cd。尽管大多数动物物种的 MT 的多功能性和异金属组成不支持这种假设，但在动物进化的根源处的一些动物谱系中存在一些例外。为了证实这一假设并进一步了解 MT 的进化，我们研究了不同蜗牛的 MT，这些 MT 以谱系特异性的方式表现出明显的 Cd 结合偏好。通过应用包括 47 种腹足纲物种的 74 个 MT 序列的代谢组学方法，并结合系统基因组学方法与分子、生化和光谱技术，我们表明蜗牛 MT 的 Cd 选择性是由金属结合域的趋同进化产生的，这些金属结合域在其一级结构上有很大的差异。我们还展示了它们的 Cd 选择性和特异性是如何通过 4.3 亿年的 MT 进化中的 Cd 的持续影响而得到优化的，通过蜗牛对不同栖息地的谱系特异性适应来改变它们。总的来说，我们的研究结果支持 Cd 在蜗牛的 MT 进化中的作用，并提供了一个有趣的例子，即一个残余的非生物因素直接驱动基因进化。最后，我们讨论了我们的发现对致力于理解导致蛋白质金属特异性的机制的研究的潜在影响，这对于设计金属选择性肽很重要。
