Department of Earth and Planetary Sciences, University of California, Davis, Davis, CA.
Harvard Medical School, Boston, MA.
Mol Biol Evol. 2022 Sep 1;39(9). doi: 10.1093/molbev/msac192.
Sirtuins are a family of proteins that protect against cellular injury and aging; understanding their evolution should reveal fundamental mechanisms governing longevity. "Early-branching" animals such as sea sponges and jellyfish have been understudied in previous analyses of sirtuin diversity. These organisms not only hold important positions at the base of the evolutionary tree, but also have unique aging dynamics that defy convention, such as quasi-immortality and high regenerative capacity. In this study, we survey the evolution of sirtuin proteins in animals, with a focus on the oldest living lineages. We describe previously unrecognized expansions of "Class IV" and "Class I" sirtuins around the origin of animals, raising the number of sirtuin families in the last common ancestor to at least nine. Most of these undescribed sirtuins have been lost in vertebrates and other bilaterian animals. Our work also clarifies the evolution of PNC1 and NAMPT enzymes that carry out the rate-limiting step in sirtuin-related NAD+ biosynthesis. The genes for PNC1 and NAMPT enzymes were both present in the first animals, with the genes being lost a minimum of 11 and 13 times, respectively, over the course of animal evolution. We propose that species with these ancestral gene repertoires are ideal model organisms for studying the genetic regulation of animal longevity and will provide clues to increasing longevity in humans.
Sirtuins 是一类能够抵抗细胞损伤和衰老的蛋白质；对其进化的理解应该能够揭示出控制寿命的基本机制。在以前对 Sirtuins 多样性的分析中，海海绵和水母等“早期分支”动物的研究较少。这些生物不仅在进化树的底部占据着重要的位置，而且还具有独特的衰老动态，例如准永生和高再生能力。在这项研究中，我们调查了动物中 Sirtuins 蛋白的进化，重点关注最古老的生物谱系。我们描述了在动物起源时“Class IV”和“Class I”Sirtuins 的先前未被识别的扩张，使最后共同祖先中的 Sirtuins 家族数量至少增加到九个。这些未被描述的 Sirtuins 中的大多数在脊椎动物和其他两侧对称动物中已经丢失。我们的工作还澄清了进行 Sirtuin 相关 NAD+生物合成限速步骤的 PNC1 和 NAMPT 酶的进化。PNC1 和 NAMPT 酶的基因都存在于第一批动物中，在动物进化过程中，这些基因分别至少丢失了 11 次和 13 次。我们提出，具有这些祖先基因库的物种是研究动物长寿的遗传调控的理想模式生物，并将为提高人类的寿命提供线索。
