Pett, WalkerAdamski, MarcinAdamska, MajaFrancis, Warren R.Eitel, MichaelPisani, DavideWorheide, Gert2019-12-180737-4038http://hdl.handle.net/1885/195776Resolving the relationships of animals (Metazoa) is crucial to our understanding of the origin of key traits such as muscles, guts, and nerves. However, a broadly accepted metazoan consensus phylogeny has yet to emerge. In part, this is because the genomes of deeply diverging and fast-evolving lineages may undergo significant gene turnover, reducing the number of orthologs shared with related phyla. This can limit the usefulness of traditional phylogenetic methods that rely on alignments of orthologous sequences. Phylogenetic analysis of gene content has the potential to circumvent this orthology requirement, with binary presence/absence of homologous gene families representing a source of phylogenetically informative characters. Applying binary substitution models to the gene content of 26 complete animal genomes, we demonstrate that patterns of gene conservation differ markedly depending on whether gene families are defined by orthology or homology, that is, whether paralogs are excluded or included. We conclude that the placement of some deeply diverging lineages may exceed the limit of resolution afforded by the current methods based on comparisons of orthologous protein sequences, and novel approaches are required to fully capture the evolutionary signal from genes within genomes.W.P. was supported by the French National Research Agency (ANR) grant Ancestrome (ANR-10-BINF-01-01), and by grants from the National Science Foundation (DEB1556615, DEB-1256993). D.P. was supported by a NERC BETR (NE/P013643/1) grant. G.W. was supported by LMU Munich’s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, and the German Research Foundation (DFG) grant Wo896/19-1, and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 764840 (ITN IGNITE)application/pdfen-AU© 2019 The Author(s)phylogenomicsgene contentanimal phylogenyhomologyorthology2019-01-2810.1093/molbev/msz0132019-08-04