The genome of Trichoplax adhaerens, a simple free-living animal, has been sequenced and analyzed, revealing a compact genome of approximately 98 million base pairs. Phylogenetic analysis suggests that placozoans belong to a eumetazoan clade that includes cnidarians and bilaterians, with sponges as the earliest diverging animals. The genome shows conserved gene content, structure, and synteny relative to human and other eumetazoan genomes. Despite its apparent simplicity, the genome encodes a rich array of transcription factors and signaling pathway genes typically associated with complex developmental processes in eumetazoans, suggesting the presence of cryptic cellular complexity. Trichoplax is a flat, disc-shaped organism with two epithelial layers and a layer of multi-nucleate fiber cells. It lacks nerves, sensory cells, and muscle cells. It feeds by using its bottom surface as a temporary gastric cavity, and moves via cilia on the bottom surface and fiber cells. It reproduces by binary fission, and sexual reproduction has not been observed in culture, though putative oocyte formation is seen in degenerating animals. The genome analysis reveals that Trichoplax has a genome with a high degree of conservation in gene structure and synteny compared to other eumetazoans. It contains a large number of protein-coding genes, many of which have homologs in other animals. The genome also shows conserved intron structures, which is unusual for small genomes. Phylogenetic analysis using 104 nuclear genes suggests that placozoans are a sister group to cnidarians and bilaterians, with demosponge sequences diverging prior to the Trichoplax-cnidarian-bilaterian clade. This is supported by parsimony analysis, though with weaker support. The results contradict some mitochondrial tree analyses, which are complicated by long branch lengths in mitochondrial peptides. The Trichoplax genome exhibits conserved synteny with other eumetazoans, including larger blocks of conserved linkage compared to the human genome. This suggests that the Trichoplax genome retains many ancestral features of its last common ancestor with cnidarians and bilaterians. The genome encodes a variety of transcription factors and signaling pathway genes, including those involved in development, patterning, and cell fate specification. These genes are typically associated with complex developmental processes in eumetazoans, suggesting that Trichoplax may have cryptic cellular complexity. The genome also contains genes involved in signaling pathways such as Wnt/beta-catenin, BMP/TGF-beta, and Notch, as well as genes involved in neuroendocrine function, extracellular matrix, and cell adhesion. These genes suggest that Trichoplax may have complex regulatory events required for growth, fission, and other processes. The genome also contains genes involved in meiosis and germ cellThe genome of Trichoplax adhaerens, a simple free-living animal, has been sequenced and analyzed, revealing a compact genome of approximately 98 million base pairs. Phylogenetic analysis suggests that placozoans belong to a eumetazoan clade that includes cnidarians and bilaterians, with sponges as the earliest diverging animals. The genome shows conserved gene content, structure, and synteny relative to human and other eumetazoan genomes. Despite its apparent simplicity, the genome encodes a rich array of transcription factors and signaling pathway genes typically associated with complex developmental processes in eumetazoans, suggesting the presence of cryptic cellular complexity. Trichoplax is a flat, disc-shaped organism with two epithelial layers and a layer of multi-nucleate fiber cells. It lacks nerves, sensory cells, and muscle cells. It feeds by using its bottom surface as a temporary gastric cavity, and moves via cilia on the bottom surface and fiber cells. It reproduces by binary fission, and sexual reproduction has not been observed in culture, though putative oocyte formation is seen in degenerating animals. The genome analysis reveals that Trichoplax has a genome with a high degree of conservation in gene structure and synteny compared to other eumetazoans. It contains a large number of protein-coding genes, many of which have homologs in other animals. The genome also shows conserved intron structures, which is unusual for small genomes. Phylogenetic analysis using 104 nuclear genes suggests that placozoans are a sister group to cnidarians and bilaterians, with demosponge sequences diverging prior to the Trichoplax-cnidarian-bilaterian clade. This is supported by parsimony analysis, though with weaker support. The results contradict some mitochondrial tree analyses, which are complicated by long branch lengths in mitochondrial peptides. The Trichoplax genome exhibits conserved synteny with other eumetazoans, including larger blocks of conserved linkage compared to the human genome. This suggests that the Trichoplax genome retains many ancestral features of its last common ancestor with cnidarians and bilaterians. The genome encodes a variety of transcription factors and signaling pathway genes, including those involved in development, patterning, and cell fate specification. These genes are typically associated with complex developmental processes in eumetazoans, suggesting that Trichoplax may have cryptic cellular complexity. The genome also contains genes involved in signaling pathways such as Wnt/beta-catenin, BMP/TGF-beta, and Notch, as well as genes involved in neuroendocrine function, extracellular matrix, and cell adhesion. These genes suggest that Trichoplax may have complex regulatory events required for growth, fission, and other processes. The genome also contains genes involved in meiosis and germ cell