The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Choanoflagellates are the closest known relatives of metazoans. To understand the molecular mechanisms underlying the evolution of metazoan multicellularity, the genome of the unicellular choanoflagellate Monosiga brevicollis was sequenced and analyzed. The genome contains approximately 9,200 intron-rich genes, including those that encode cell adhesion and signaling protein domains typically found in metazoans. The study shows that the physical linkages among protein domains differ between M. brevicollis and metazoans, suggesting that domain shuffling occurred after the divergence of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows for a more detailed reconstruction of the genomic changes that accompanied the origin of metazoans. Choanoflagellates have long been of interest to evolutionary biologists due to their similarity to the feeding cells of sponges and their potential as the closest living relatives of metazoans. Evidence supporting this relationship has accumulated from phylogenetic analyses, comparative genomics, and the identification of homologues of metazoan signaling and adhesion genes. Studies show that choanoflagellates are not derived from metazoans but represent a distinct lineage that evolved before the origin of metazoans. Choanoflagellates are abundant and globally distributed microbial eukaryotes found in marine and freshwater environments. They have a unicellular life-history stage and can form simple colonies, although these differ from the differentiated cell associations in metazoans. Studies of basal metazoans indicate that the ancestral metazoan was multicellular with differentiated cell types, an epithelium, a body plan, and regulated development. In contrast, the last common ancestor of choanoflagellates and metazoans was unicellular or capable of forming simple colonies, highlighting the biological innovation that accompanied metazoan origins. Despite their evolutionary and ecological importance, little is known about the genetics and cell biology of choanoflagellates. To gain insight into their biology and reconstruct the genomic changes associated with the early evolution of metazoans, the genome of M. brevicollis was sequenced and compared with genomes from metazoans and other eukaryotes. The M. brevicollis genome contains approximately 9,200 genes and is comparable in size to the genomes of filamentous fungi and other free-living unicellular eukaryotes. M. brevicollis genes are intron-rich, with short introns compared to metazoan introns. Comparisons of intron positions in conserved genes from M. brevicollis, metazoans, and other eukaryotes reveal that the last common ancestor of choanoflagThe genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Choanoflagellates are the closest known relatives of metazoans. To understand the molecular mechanisms underlying the evolution of metazoan multicellularity, the genome of the unicellular choanoflagellate Monosiga brevicollis was sequenced and analyzed. The genome contains approximately 9,200 intron-rich genes, including those that encode cell adhesion and signaling protein domains typically found in metazoans. The study shows that the physical linkages among protein domains differ between M. brevicollis and metazoans, suggesting that domain shuffling occurred after the divergence of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows for a more detailed reconstruction of the genomic changes that accompanied the origin of metazoans. Choanoflagellates have long been of interest to evolutionary biologists due to their similarity to the feeding cells of sponges and their potential as the closest living relatives of metazoans. Evidence supporting this relationship has accumulated from phylogenetic analyses, comparative genomics, and the identification of homologues of metazoan signaling and adhesion genes. Studies show that choanoflagellates are not derived from metazoans but represent a distinct lineage that evolved before the origin of metazoans. Choanoflagellates are abundant and globally distributed microbial eukaryotes found in marine and freshwater environments. They have a unicellular life-history stage and can form simple colonies, although these differ from the differentiated cell associations in metazoans. Studies of basal metazoans indicate that the ancestral metazoan was multicellular with differentiated cell types, an epithelium, a body plan, and regulated development. In contrast, the last common ancestor of choanoflagellates and metazoans was unicellular or capable of forming simple colonies, highlighting the biological innovation that accompanied metazoan origins. Despite their evolutionary and ecological importance, little is known about the genetics and cell biology of choanoflagellates. To gain insight into their biology and reconstruct the genomic changes associated with the early evolution of metazoans, the genome of M. brevicollis was sequenced and compared with genomes from metazoans and other eukaryotes. The M. brevicollis genome contains approximately 9,200 genes and is comparable in size to the genomes of filamentous fungi and other free-living unicellular eukaryotes. M. brevicollis genes are intron-rich, with short introns compared to metazoan introns. Comparisons of intron positions in conserved genes from M. brevicollis, metazoans, and other eukaryotes reveal that the last common ancestor of choanoflag