Schematic representation of the phylogenetic pipeline used to reconstruct the human phylome. Each protein sequence encoded in the human genome is compared against a database of proteins from 39 fully sequenced eukaryotic genomes (Table 1) to select putative homologous proteins. Groups of homologous sequences are aligned and subsequently trimmed to remove gap-rich regions. The refined alignment is used to build a NJ tree, which is then used as a seed tree to perform a ML likelihood analysis as implemented in PhyML, using four different evolutionary models (five in the case of mitochondrially encoded proteins). The ML tree with the maximum likelihood is further refined with a Bayesian analysis using MrBayes. Finally, different algorithms are used to search for specific topologies in the phylome or to define orthology and paralogy relationships.