The genome of the softshell clam mya arenaria and the evolution of apoptosis

Abstract

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 clamMya arenaria provides an opportunity to re-evaluate the evolution of the geneticmachinery of apoptosis. Here, we report thewhole-genome sequence forM. arenariawhichwe leveragewith existing data to test evolutionary hypotheses on the originsof apoptosis in animals.We showthat the ancestralbilaterianp53 locus, amaster regulator of apoptosis, possessed a complex domain structure, in contrast to that of extant ecdysozoan p53s. Further, ecdysozoan taxa, but not chordates or lophotrochozoans likeM. arenaria, show a widespread reduction in apoptosis gene copy number. Finally, phylogenetic exploration of apoptosis gene copy number reveals a striking linkagewith 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.