Figure 3. Gene origin and age are not uniquely defined in the human MaGuK superfamily.

The membrane-associated guanylate kinase (MaGuK) superfamily is a multigene family with complex substructure and domain architecture. There are many potential choices for the MaGuK progenitor, which span a broad range of times. (a) MaGuK gene tree inferred from the guanylate kinase domain. Nodes 1–3 show three possible origins for MPP1: (1) the origin of the entire MaGuK family (pre-Opisthokonts), (2) the duplication that gave rise to separate CASK and MPP1 genes (pre-Metazoan), (3) the common ancestor of MPP1 and its orthologs (pre-Craniata). Domain architectures are shown on the leaves. Clades of genes with identical domain architectures are collapsed (e.g., MAGI1–3). (b) Species tree showing lineages when domains and specific MaGuKs first appeared. Leaves are decorated with the domains that are present in that species. Arrows indicate when the progenitor of a subfamily first arose, with the subfamily listed below that arrow. Red arrows indicate duplication events that either expanded a subfamily or gave rise to a new one. Branches 1, 2, and 3 represent three possible ages for MPP1, and correspond to nodes 1, 2, and 3, respectively, in the gene tree. Domain origins were inferred using Dollo parsimony with Count [36]. Gene origins are based on phylogenetic analysis [41] and Dollo parsimony.