Mafft-einsi was used, with default settings, to create a multiple sequence alignment (MSA) for the vertebrate protein sequences [26] . The MSAs were thereafter examined and refined in Jalview 2.5.1 [27] , i.e. the sequences were trimmed and well conserved and aligned regions were kept, which included 82 aligned amino acid columns. Phylogenetic analysis was performed with a Bayesian approach implemented in MrBayes [28] . The following settings for the eukaryote proteins were adjusted: The analysis was run using a gamma shaped model for the variation of evolutionary rates across sites (rates = gamma) and the mixed option (aamodelpr = mixed) was used to estimate the best amino acid substitution model. We generated 5 000 000 trees and the Markov chain Monte Carlo analysis reached well below a standard deviation of split frequencies of 0.01. Each hundred tree was sampled from the mcmc run and the first 25% of the sampled trees were discarded (burnin = 0.25) to reassure a good sample from the posterior probability distribution. A consensus tree was built from the remaining 37 500 trees with the MrBayes sumt command using the 50% majority rule method. The sump command was used to assure that an adequate sample of the posterior probability distribution was reached during the mcmc procedure. To validate the phylogenetic inference with MrBayes a maximum likelihood method implmemented in RAxML was used [29] . The combined rapid bootstrapping and search for the bestscoring ML tree option (-f a) in RAxML was used to create 1000 bootstraps (-# 1000) using a gamma model of evolutionary rates and the JTT substitution model (-m PROTGAMMAJTT). The JTT substitution model was identified as the most suitable model in the Bayesian analysis and therefore selected for the maximum likelihood phylogeny. The consensus phylogenetic tree found with MrBayes was drawn in Dendroscope 3.0 and the bootstrap support values from RAxML were annotated on the corresponding nodes [30] . The phylogenetic tree was used to determine subfamilies by identifying clusters with a high posterior probability and bootstrap support. Invertebrate sequences were excluded from the phylogenetic analysis as they induced highly unstable topologies together with 1 M. musculus, 2 D. rerio and 3 X. tropicalis sequences. These excluded sequences were categorized into their respective subfamilies by using a BLAST search towards the categorized sequences. The top five hits were examined to classify the invertebrate and excluded sequences into subfamilies. A sequence was assigned to the subfamily if four out of the five top hits are from the same subfamily.