Emergence of distinct syntenic density regimes is associated with early metazoan genomic transitions.

BACKGROUND: Animal genomes are strikingly conserved in terms of local gene order (microsynteny). While some of these microsyntenies have been shown to be coregulated or to form gene regulatory blocks, the diversity of their genomic and regulatory properties across the metazoan tree of life remains largely unknown. RESULTS: Our comparative analyses of 49 animal genomes reveal that the largest gains of synteny occurred in the last common ancestor of bilaterians and cnidarians and in that of bilaterians. Depending on their node of emergence, we further show that novel syntenic blocks are characterized by distinct functional compositions (Gene Ontology terms enrichment) and gene density properties, such as high, average and low gene density regimes. This is particularly pronounced among bilaterian novel microsyntenies, most of which fall into high gene density regime associated with higher gene coexpression levels. Conversely, a majority of vertebrate novel microsyntenies display a low gene density regime associated with lower gene coexpression levels. CONCLUSIONS: Our study provides first evidence for evolutionary transitions between different modes of microsyntenic block regulation that coincide with key events of metazoan evolution. Moreover, the microsyntenic profiling strategy and interactive online application (Syntenic Density Browser, available at: http://synteny.csb.univie.ac.at/ ) we present here can be used to explore regulatory properties of microsyntenic blocks and predict their coexpression in a wide-range of animal genomes.

Retinoic acid signaling and neurogenic niche regulation in the developing peripheral nervous system of the cephalochordate amphioxus.

The retinoic acid (RA) signaling pathway regulates axial patterning and neurogenesis in the developing central nervous system (CNS) of chordates, but little is known about its roles during peripheral nervous system (PNS) formation and about how these roles might have evolved. This study assesses the requirement of RA signaling for establishing a functional PNS in the cephalochordate amphioxus, the best available stand-in for the ancestral chordate condition. Pharmacological manipulation of RA signaling levels during embryogenesis reduces the ability of amphioxus larvae to respond to sensory stimulation and alters the number and distribution of ectodermal sensory neurons (ESNs) in a stage- and context-dependent manner. Using gene expression assays combined with immunohistochemistry, we show that this is because RA signaling specifically acts on a small population of soxb1c-expressing ESN progenitors, which form a neurogenic niche in the trunk ectoderm, to modulate ESN production during elongation of the larval body. Our findings reveal an important role for RA signaling in regulating neurogenic niche activity in the larval amphioxus PNS. Although only few studies have addressed this issue so far, comparable RA signaling functions have been reported for neurogenic niches in the CNS and in certain neurogenic placode derivatives of vertebrates. Accordingly, the here-described mechanism is likely a conserved feature of chordate embryonic and adult neural development.

Robust 3D modeling reveals spatiosyntenic properties of animal genomes.

Animal genomes are organized into chromosomes that are remarkably conserved in their gene content, forming distinct evolutionary units (synteny). Using versatile chromosomal modeling, we infer three-dimensional topology of genomes from representative clades spanning the earliest animal diversification. We apply a partitioning approach using interaction spheres to compensate for varying quality of topological data. Using comparative genomics approaches, we test whether syntenic signal at gene pair, local, and whole chromosomal scale is reflected in the reconstructed spatial organization. We identify evolutionarily conserved three-dimensional networks at all syntenic scales revealing novel evolutionarily maintained interactors associated with known conserved local gene linkages (such as hox). We thus present evidence for evolutionary constraints that are associated with three-, rather than just two-, dimensional animal genome organization, which we term spatiosynteny. As more accurate topological data become available, together with validation approaches, spatiosynteny may become relevant in understanding the functionality behind the observed conservation of animal chromosomes.

Ancestral Role of Ecdysis-Related Neuropeptides in Animal Life Cycle Transitions.

Ecdysis or molting evolved ∼535 mya in Ecdysozoa, the most diverse and species-rich animal superphylum.1 A cascade of ecdysis-related neuropeptides (ERNs) controls the innate behavioral programs required for cuticle shedding in some ecdysozoan lineages (e.g., arthropods)2-12 but is lacking in others (e.g., nematodes).13 We recently reported on the surprisingly ancient bilaterian origin of key ERNs, such as eclosion hormone (EH), crustacean cardioactive neuropeptide (CCAP), myoinhibitory peptide (MIP), bursicon alpha (Bursα), and bursicon beta (Bursß).13,14 Thus, ERNs far predate the emergence of ecdysis, but the question as to their ancestral functions remains unresolved. Here, we compare the ERN toolkits and temporal expression profiles of six ecdysozoans (tardigrades, crustaceans, and insects), eight lophotrochozoans (planarians, annelids, and mollusks), and five deuterostomes (crinoids, sea urchins, and hemichordates). Our results show that the major, coordinated upregulation of ERNs always coincides with a transition between key life history stages, such as hatching in direct developers and metamorphosis in indirect developers. This implies that ERNs already played an ancestral role in the switch from embryonic or larval ontogeny to juvenile maturation in the last common ancestor of Nephrozoa. Consequently, the transcriptional signature of invertebrate life cycle transitions presented here was already in place in the Precambrian and was only secondarily co-opted into regulating the molting process at the dawn of Ecdysozoa.

Ecdysis-related neuropeptide expression and metamorphosis in a non-ecdysozoan bilaterian.

Ecdysis-related neuropeptides (ERNs), including eclosion hormone, crustacean cardioactive peptide, myoinhibitory peptide, bursicon alpha, and bursicon beta regulate molting in insects and crustaceans. Recent evidence further revealed that ERNs likely play an ancestral role in invertebrate life cycle transitions, but their tempo-spatial expression patterns have not been investigated outside Arthropoda. Using RNA-seq and in situ hybridization, we show that ERNs are broadly expressed in the developing nervous system of a mollusk, the polyplacophoran Acanthochitona fascicularis. While some ERN-expressing neurons persist from larval to juvenile stages, others are only present during settlement and metamorphosis. These transient neurons belong to the "ampullary system," a polyplacophoran-specific larval sensory structure. Surprisingly, however, ERN expression is absent from the apical organ, another larval sensory structure that degenerates before settlement is completed in A. fascicularis. Our findings thus support a role of ERNs in A. fascicularis metamorphosis but contradict the common notion that the apical organ-like structures shared by various aquatic invertebrates (i.e., cnidarians, annelids, mollusks, echinoderms) are of general importance for this process.

Ancient animal genome architecture reflects cell type identities.

The level of conservation of ancient metazoan gene order (synteny) is remarkable. Despite this, the functionality of the vast majority of such regions in metazoan genomes remains elusive. Utilizing recently published single-cell expression data from several anciently diverging metazoan species, we reveal the level of correspondence between cell types and genomic synteny, identifying genomic regions conferring ancient cell type identity.