In this thesis, evolutionary models and frameworks for studying protein coding sequence evolution in the Metazoa are explored. The Metazoa refers to all multicellular animals. The models and frameworks applied are phylogeny and network based – we propose that both approaches are necessary to understand the various mechanisms of protein evolution that can be involved in protein family evolution. Firstly, we apply a phylogenetic approach to assess whether the additional parameterisation and computational requirements associated with heterogeneous modelling can be justified in terms of model fit and adequacy. The question addressed in Chapter 2 is whether we can accurately and adequately model the position of the placental mammal root. We show that model misspecification has resulted in the conflicting positions for the root of the placental mammal phylogeny in the recent literature. Therefore, inadequate models can result in wrong inferences about the evolutionary history of the sequences. Indeed, phylogenetic models may not be appropriate for the evolutionary process at work, for example in the case of recombinatorial processes. Therefore, Chapters 3 and 4 focus on the application of network theory, and specifically sequence similarity networks, to model the evolution of protein coding sequences by gene fission/fusion and domain shuffling – referred to throughout as gene remodelling events. Little is known about the contribution of these remodelling events in protein evolution and in the evolution of the Metazoa in particular. These are innovations in the protein coding sequences that are brought about by shuffling of regions of DNA from different proteins (this is not direct descent with modification and therefore not strictly phylogenetic in nature as it requires multiple roots on the phylogenetic tree). In this thesis, we describe the application of phylogenetic and network based models of protein coding evolution to sequence data from all major groups across the Metazoa and we define the basic characteristics and rules for gene remodelling in the Metazoa.