title: Origin and evolution of the metazoan non-coding regulatory genome.
abstract: Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa. High-throughput next-generation sequencing, largely in bilaterian model species, has led to the discovery of tens of thousands of non-coding RNA genes (ncRNAs), including short, long and circular forms, and uncovered the central roles they play in development. Based on the analysis of non-bilaterian metazoan, unicellular holozoan and fungal genomes, the evolution of some ncRNAs, such as Piwi-interacting RNAs, correlates with the emergence of metazoan multicellularity, while others, including microRNAs, long non-coding RNAs and circular RNAs, appear to be more ancient. Analysis of non-coding regulatory DNA and histone post-translational modifications have revealed that some cis-regulatory mechanisms, such as those associated with proximal promoters, are present in non-animal holozoans, while others appear to be metazoan innovations, most notably distal enhancers. In contrast, the cohesin-CTCF system for regulating higher-order chromatin structure and enhancer-promoter long-range interactions appears to be restricted to bilaterians. Taken together, most bilaterian non-coding regulatory mechanisms appear to have originated before the divergence of crown metazoans. However, differential expansion of non-coding RNA and cis-regulatory DNA repertoires in bilaterians may account for their increased regulatory and morphological complexity relative to non-bilaterians.
authors.affiliation: School of Biological Sciences, University of Queensland, Brisbane, Australia. Electronic address: federico.gaiti@gmail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Gaiti
authors.affiliation: Department of Integrative Zoology, University of Vienna, Vienna, Austria. Electronic address: andrew.calcino@univie.ac.at.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Calcino
authors.affiliation: School of Biological Sciences, University of Queensland, Brisbane, Australia. Electronic address: m.tanurdzic@uq.edu.au.
authors.forename: Miloš
authors.initials: M
authors.lastname: Tanurdžić
authors.affiliation: School of Biological Sciences, University of Queensland, Brisbane, Australia. Electronic address: b.degnan@uq.edu.au.
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Degnan
mesh_terms: D000818:Animals; D005075:Biological Evolution; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid
keywords: Cis-regulation; Complexity; Enhancers; Evolution; Gene regulation; Holozoans; Metazoans; Multicellularity; Non-coding RNAs