Evolution of the Metazoan Protein Domain Repertoire Revealed by a Birth-Death-Gain Model

Reconstruction of the ancestral protein repertoire offers valuable insights into the tempo and mode of protein content evolution, but can be highly sensitive to model choice. We used a phylogenetic Birth-Death-Gain model to investigate the evolution of the metazoan protein domain repertoire. Domains, protein modules with a distinct structure and function, represent the basic components of protein repertoire.  Given a species tree and a census of protein domain families in present-day species, we estimated the most likely rates of domain family origination, duplication, and loss. Rates were allowed to vary across species lineages and domain families, decoupling these factors. Statistical hierarchical clustering of family-specific rates reveals groups of domains evolving in concert. Moreover, we observe a strong and significant association between family rate and family function.  Interestingly, families with functions associated with metazoan innovations tend to have the fastest rates. We further inferred the expected ancestral domain content and the history of domain family gains, losses, expansions, and contractions in each species lineage. Our analysis reveals an ongoing process of domain family replacement and resizing, consistent with extensive remodeling of the protein domain repertoire. This stands in contrast to recent reports of widespread loss during metazoan evolution, which were obtained with more constrained models. The use of a powerful, probabilistic Birth-Death-Gain model reveals an unexpected level of genomic plasticity.