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Modern biology has been revolutionized by the advent of comparative molecular sequence data and powerful methods of phylogenetic analysis that allow us greater insight into evolutionary history than ever before. Rapid development of bioinformatics and avalanche of genomic data from a great variety of organisms make it timely and feasible to ascertain evolutionary affinities within and among major branches of the tree of life using extensive molecular evidence. In this context, inferring deep phylogeny of Metazoa (largely represented by multicellular animals with true tissues and complex body plan) in many respects is considered a priority . The diversity of extant animal body plans far exceeds that accommodated in modern phylogenies, many are represented by aberrant, often neglected phyla with traditionally disputable evolutionary affinities. In this study, full advantage was taken of the bulk of existing, and continuously accumulating, genomic data to build phylogenetically informative datasets with extensive sampling of animal diversity. A host of techniques, including original methods, was employed to mine for homologous genetic markers in databases containing complete metazoan genomes and EST libraries, assembling and translating ESTs, assessing markers’ orthology and their informativity for establishing large-scale relationships. Original methods were used to control for quality of multiple sequence alignments of the found markers via reducing the amount of uninformative “noisy” columns thus providing for the best possible resolution of individual-marker trees. A constructed dataset contains 51 genes from 30 animal species of 11 phyla constituting a representative sample of extant metazoan diversity (Ctenophora, Cnidaria, Priapulida, Tardigrada, Platyhelminthes, Nematoda, Arthropoda, Annelida, Mollusca, Echinodermata, Chordata). Currently in phylogenomics, a multigene dataset for more than four phyla is obtained for the first time. It is used in sophisticated phylogenetic analyses to build a tree of the Metazoa based on total evidence from the 51 gene and on combining individual gene trees into a supertree. The outcome of this analyses provides important new knowledge and insights into a number of fundamental biological questions, e.g. ancestral nature of the metazoan body plan, origins of the secondary body cavity (coelom) among the bilaterally symmetric animals and its fate in groups currently considered acoelomic, such as nematodes and flatworms.