Xenacoelomorpha are simple, marine worms with net-like nervous systems, no circulatory or respiratory systems and a blind gut. The phylogenetic position of Xenacoelomorpha is the subject of ongoing debate in the literature. The two possible locations for the Xenacoelomorpha within the animal tree are i) as the sister clade to all other bilaterians and ii) as deuterostomes, closely related to the Ambulacraria (echinoderms and hemichordates). The understanding of the phylogenetic position of Xenacoelomorpha has major implications in understanding the appearance of the Bilateria last common ancestor and the direction of the evolutionary process within the animal kingdom. If Xenacoelomorpha are in fact basal bilaterians, they can resemble many similarities to simple acoel-like bilaterian ancestor. However, if Xenacoelomorpha are sister group to Ambulacraria, they likely secondary simplified from a complex, segmented, coelomate Bilateria ancestor. I analysed the quality of 6 new xenacoelomorph genomic and 7 transcriptomic data sets (Symsagittifera roscoffensis, Pseudophanostoma variabilis, Paratomella rubra and Praesagittifera naikaiensis, the nemertodermatids Meara stichopi and Nemertoderma westbladi and the xenoturbellid Xenoturbella bocki), and have constructed comprehensive datasets of xenacoelomorph proteins (proteomes (entire set of proteins expressed by a specific organism (UniProt Consortium, 2010))). I used these, together with proteomes from 60 other species, to construct a database of gene families, which have descended from the same common ancestor within the broad range of 67 species within the animal kingdom. Based on inferred orthology/paralogy relations within 2 these families, I reconstructed the duplications, gains and losses of genes across the Metazoa. The analysis of ancestral gene family content is suggestive for the phylogenetic position of the Xenacoelomorpha, as ancestral Xenacoelomorpha gene content is more similar to inferred Xenambulacraria gene content then to ancestral Bilateria gene content. Moreover, Xenacoelomorpha show more simultaneous gene losses with Ambulacraria then with other major Bilateria clades. To reconstruct a molecular phylogenetic tree of Xenacoelomorpha, I first established a bioinformatics pipeline for large-scale molecular phylogeny reconstruction, by comparing 3 commonly used automated methods for orthology and paralogy prediction (OMA, CEGMA, OrthoMCL). I tested the application of these methods in constructing phylogenetic matrices from high throughput sequencing data. I used the best performing pipeline to infer the species tree involving 8 Xenacoelomorpha species. Our phylogenetic analysis tentatively supports the placement of Xenacoelomorpha as a sister group of Ambulacrari
