Phylogenetic tracing of midbrain-specific regulatory sequences suggests single origin of eubilaterian brains

Conserved cis-regulatory elements (CREs) control Engrailed-, Pax2-, and dachshund-related gene expression net-works directing the formation and function of corresponding midbrain circuits in arthropods and vertebrates. Polarized outgroup analyses of 31 sequenced metazoan genomes representing all animal clades reveal the emergence of Pax2- and dachshund-related CRE-like sequences in anthozoan Cnidaria. The full complement, including Engrailed-related CRE-like sequences, is only detectable in spiralians, ecdysozoans, and chordates that have a brain; they exhibit comparable genomic locations and extensive nucleotide identities that reveal the presence of a conserved core domain, all of which are absent in non-neural genes and, together, distinguish them from randomly assembled sequences. Their presence concurs with a genetic boundary separating the rostral from caudal nervous systems, demonstrated for the metameric brains of annelids, arthropods, and chor-dates and the asegmental cycloneuralian and urochordate brain. These findings suggest that gene regulatory networks for midbrain circuit formation evolved within the lineage that led to the common ancestor of proto-stomes and deuterostomes.

Automated summary

Conserved cis-regulatory elements (CREs) control the expression networks of Engrailed-, Pax2-, and dachshund-related genes, directing the formation and function of midbrain circuits in arthropods and vertebrates. Analysis of 31 sequenced genomes from different animal clades reveals the presence of Pax2- and dachshund-related CRE-like sequences in anthozoan Cnidaria. The full complement, including Engrailed-related CRE-like sequences, is found in spiralians, ecdysozoans, and chordates with a brain, indicating a conserved core domain that distinguishes these genes from randomly assembled sequences.