Autophagy genes across the tree of life: from prokaryotic homologs to eukaryotic complexity

Abstract Macroautophagy (referred to as autophagy hereafter) is an intracellular degradation system essential for cell homeostasis. It requires the concerted actions of around 20 autophagy-related ( ATG ) genes, as well as components from the cytoskeleton and the endomembrane systems. The autophagy pathway likely already existed in the last eukaryotic common ancestor (LECA) and subsequently diversified in different lineages. While the pathway itself does not exist in prokaryotes, some ATG genes have prokaryotic remote homologs. In this Review, we summarize recent advances in three areas related to the evolution of the autophagy pathway, and discuss possible future directions: (1) the evolutionary context surrounding the emergence of the autophagy pathway during eukaryogenesis; (2) evolutionary diversifications of the ATG genes in different eukaryotic lineages through gene duplications, losses, and lineage-specific gains; and (3) the functions that the remote homologs of the ATG genes carried out in prokaryotes, and the phylogenetic and evolutionary relationships between the eukaryotic and prokaryotic genes.