Table S1 Invasion criteria in the entropy model. *''a.s. = Almost surely'' refers to the fact the result is a stochastic process. The criteria for large and small population size are defined in more detail in Demetrius et al. [19] . The criteria noted in Table S1 have been tested against simulation where they have been shown to be replicated. Found at: doi:10.1371/journal.pone.0012951.s001 (0.07 MB DOC) Figure S1 Life cycle for an infective corresponding to the matrix in equation S1 with 4 infectious age classes.  The Nature of Protein Domain Evolution: Shaping the Interaction Network The proteomes that make up the collection of proteins in contemporary organisms evolved through recombination and duplication of a limited set of domains. These protein domains are essentially the main components of globular proteins and are the most principal level at which protein function and protein interactions can be understood. An important aspect of domain evolution is their atomic structure and biochemical function, which are both specified by the information in the amino acid sequence. Changes in this information may bring about new folds, functions and protein architectures. With the present and still increasing wealth of sequences and annotation data brought about by genomics, new evolutionary relationships are constantly being revealed, unknown structures modeled and phylogenies inferred. Such investigations not only help predict the function of newly discovered proteins, but also assist in mapping unforeseen pathways of evolution and reveal crucial, co-evolving inter- and intra-molecular interactions. In turn this will help us describe how protein domains shaped cellular interaction networks and the dynamics with which they are regulated in the cell. Additionally, these studies can be used for the design of new and optimized protein domains for therapy. In this review, we aim to describe the basic concepts of protein domain evolution and illustrate recent developments in molecular evolution that have provided valuable new insights in the field of comparative genomics and protein interaction networks. The protein universe is the collection of proteins of all biological species that exist or have once existed on Earth [1] . Our sampling and understanding of it began over half a century ago, when the first peptide and protein sequences were determined by Sanger [2, 3] and, subsequently, the sequencing of RNA and DNA [4] [5] [6] . In the meantime, the genome projects of the last decade have uncovered an overwhelming amount of sequence data and researchers are now starting to address a series of fundamental questions that should shed light onto protein evolution processes [7] [8] [9] [10] . For instance, how many gene encoding sequences are present in one genome? How many sequences are repetitive and are these sequences similar in the various organisms on Earth? Which genes were involved in the large scale genome duplications that we see in animals?