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.

中文翻译：

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软壳蛤的基因组和细胞凋亡的进化。

细胞凋亡是多细胞动物的一个基本特征，在哺乳动物、果蝇和线虫中得到最好的理解，无脊椎动物模型被认为代表了一种祖先简单的情况。然而，软壳蛤Mya arenararia 中白血病样癌症的存在为重新评估细胞凋亡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，我们利用现有数据来测试关于动物细胞凋亡起源的进化假设。我们表明，与现存的蜕皮动物 p53s 相比，祖先的双侧 p53 基因座是细胞凋亡的主要调节器，具有复杂的结构域结构。此外，蜕皮动物类群，但不是脊索动物或 lophotrochozoans，如M. arenaria显示出细胞凋亡基因拷贝数的普遍减少。最后，细胞凋亡基因拷贝数的系统发育探索揭示了跨物种的 p53 结构域复杂性的显着联系。我们的结果挑战了目前对细胞凋亡进化的理解，并突出了双边细胞凋亡工具包的祖先复杂性及其在蜕皮动物辐射期间的后续拆除。