The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores, or comb jellies, have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here, we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well-recognized in ctenophores, many bilaterian neuron-specific genes and genes of “classical” neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.

The full complement of homeobox transcription factor sequences, including genes and pseudogenes, was determined from the analysis of 10 complete genomes from flowering plants, moss, Selaginella, unicellular green algae, and red algae. Our exhaustive genome-wide searches resulted in the discovery in each class of a greater number of homeobox genes than previously reported. All homeobox genes can be unambiguously classified by sequence evolutionary analysis into 14 distinct classes also characterized by conserved intron–exon structure and by unique codomain architectures. We identified many new genes belonging to previously defined classes (HD-ZIP I to IV, BEL, KNOX, PLINC, WOX). Other newly identified genes allowed us to characterize PHD, DDT, NDX, and LD genes as members of four new evolutionary classes and to define two additional classes, which we named SAWADEE and PINTOX. Our comprehensive analysis allowed us to identify several newly characterized conserved motifs, including novel zinc finger motifs in SAWADEE and DDT. Members of the BEL and KNOX classes were found in Chlorobionta (green plants) and in Rhodophyta. We found representatives of the DDT, WOX, and PINTOX classes only in green plants, including unicellular green algae, moss, and vascular plants. All 14 homeobox gene classes were represented in flowering plants, Selaginella, and moss, suggesting that they had already differentiated in the last common ancestor of moss and vascular plants.

Ctenophora, compromising approximately 200 described species, is an important lineage for understanding metazoan evolution and is of great ecological and economic importance. Ctenophore diversity includes species with unique colloblasts used for prey capture, smooth and striated muscles, benthic and pelagic lifestyles, and locomotion with ciliated paddles or muscular propulsion. However, ancestral states of traits are debated and relationships among many lineages are unresolved. Here, using 27 newly sequenced ctenophore transcriptomes, publicly available data, and methods to control systematic error we establish the placement of Ctenophora as the sister group to all other animals and refine phylogenetic relationships within ctenophores. Molecular clock analyses suggest modern ctenophore diversity originated approximately 350MYA ± 88 MY, conflicting with previous hypotheses of approximately 65 MYA. We recover Euplokamis dunlapae, a species with striated muscles, as the sister lineage to other sampled ctenophores. Ancestral state reconstruction shows the most recent common ancestor of extant ctenophores was pelagic, possessed tentacles, was bioluminescent, and did not have separate sexes. Our results imply at least two transitions from a pelagic to a benthic lifestyle within Ctenophora, suggesting such transitions were more common in animal diversification than appreciated.