Molecular, Cellular and Biomedical Sciences, University of New Hampshire.
School of Marine Science and Ocean Engineering, University of New Hampshire.
Genome Biol Evol. 2020 Oct 1;12(10):1681-1693. doi: 10.1093/gbe/evaa143.
Apoptosis is a fundamental feature of multicellular animals and is best understood in mammals, flies, and nematodes, with the invertebrate models being thought to represent a condition of ancestral simplicity. However, the existence of a leukemia-like cancer in the softshell clam Mya arenaria provides an opportunity to re-evaluate the evolution of the genetic machinery of apoptosis. Here, we report the whole-genome sequence for M. arenaria which we leverage with existing data to test evolutionary hypotheses on the origins of apoptosis in animals. We show that the ancestral bilaterian p53 locus, a master regulator of apoptosis, possessed a complex domain structure, in contrast to that of extant ecdysozoan p53s. Further, ecdysozoan taxa, but not chordates or lophotrochozoans like M. arenaria, show a widespread reduction in apoptosis gene copy number. Finally, phylogenetic exploration of apoptosis gene copy number reveals a striking linkage with p53 domain complexity across species. Our results challenge the current understanding of the evolution of apoptosis and highlight the ancestral complexity of the bilaterian apoptotic tool kit and its subsequent dismantlement during the ecdysozoan radiation.
细胞凋亡是多细胞动物的一个基本特征，在哺乳动物、果蝇和线虫中研究得最为透彻，无脊椎动物模型被认为代表了一种原始的简单状态。然而，软壳蛤 Mya arenaria 中存在一种类似白血病的癌症，为重新评估细胞凋亡的遗传机制的进化提供了机会。在这里，我们报告了 M. arenaria 的全基因组序列，并利用现有数据来检验关于细胞凋亡在动物中起源的进化假说。我们表明，凋亡的祖先两侧对称动物 p53 基因座，是凋亡的主要调控因子，拥有复杂的结构域，与现存的节肢动物 p53s 不同。此外，节肢动物类群，而不是脊索动物或像 M. arenaria 这样的螺旋动物类群，显示出凋亡基因拷贝数的广泛减少。最后，对凋亡基因拷贝数的系统发育探索揭示了一个显著的联系，即跨越物种的 p53 结构域复杂性。我们的研究结果挑战了细胞凋亡进化的现有认识，并强调了两侧对称动物凋亡工具包的原始复杂性及其在节肢动物辐射过程中的后续解体。
