Abstract
Inhibitors of apoptosis (IAPs) are key regulators of apoptosis that inhibit caspase activity by sterically blocking their active site, sequestering them or promoting their degradation by the proteasome. However, recent reports show that the role of IAPs may be much broader and that they may be involved in the regulation of important non-apoptotic cellular processes such as cell division, cell migration, signal transduction, autophagy or innate immunity. This makes IAPs important cellular players.From an evolutionary point of view, IAPs form a large multigenic protein family characterised by a high degree of diversity in both sequence and functional architecture. Present-day animal lineages have very different IAP repertoires, with some species having a small number of IAPs (2 genes in the nematode Caenorhabditis elegans), while in others, such as the hard clam Mercenaria mercenaria, the number of IAP-coding genes exceeds 150. This reflects a very complex but poorly understood evolutionary history, the understanding of which could shed light on the evolution of key cellular processes.To go further, we analysed 2,843 IAPs from 312 species, covering all major animal groups, revealing even greater diversity than expected. We identified 121 different domain architectures, most of which are found in a limited number of species. This illustrates the huge evolutionary potential of IAPs and the ability of metazoans to modulate their IAP repertoires. It also highlights the challenges of studying the evolution of IAPs. Nevertheless, using an accurate phylogenomic approach, we have identified a set of four ancient IAPs in metazoans that have been conserved and that have given rise to the incredible diversity of IAPs observed in animals today. We have also traced the history of IAPs in the major metazoan phyla, with a particular focus on the protostomes. This study provides a detailed evolutionary framework for metazoan IAPs, which will serve as the basis for future studies.