Close relatives, sharing an overall sequence identity above for example 50% and a set of functional properties, can also be grouped into families and subfamilies. In turn, these families share also evolutionary relationships with other domains and form together so-called domain superfamilies [18, 35] . Evolutionary distances between related domain sequences can easily be estimated from sequence alignments, provided that the correct rate assumptions are made. Subsequently, these can be used to compute the phylogenies of the domain that share an evolutionary history. These, often tree-like graphs (Fig. 1B) , depend heavily on rate variation models, such as molecular clocks or relaxed molecular clocks (e.g., Maximum Likelyhood and Bayesian estimation), which are calibrated with additional evidence Fig. (1A) . It was computed using Bayesian estimation and presents the best-supported topology for the alignment. Numbers indicate % support by the two methods used, while # indicates gene duplication events in the common ancestor and * marks a species-specific duplication event. For computational details, please see [42] . such as fossils and may therefore also provide valuable information on aspects like divergence times and ancestral sequences [36] [37] [38] . Commonly used phylogenetic analysis strategies are listed in Table 1 .