Organisation and turnover of developmental regulatory elements in Metazoan genomes

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Syntenic arrays of extremely conserved non-coding elements (CNEs) regulate key developmental genes in multiple diverse Metazoan lineages. Due to a lack of sequence conservation between CNEs across distant lineages, it has been proposed that this form of long-range gene regulation has been acquired independently in multiple lineages. Our alternative hypothesis is that while these sequences are extremely conserved within a lineage, no sequence is totally indispensable and therefore given enough time, sequence turnover within CNEs would make their identification between lineages impossible. By analysing deeply and shallowly conserved arrays of CNEs, known as genomic regulatory blocks (GRBs), in three metazoan lineages, and find that in all three, deeply and shallowly conserved GRBs target distinct subsets of genes: the most conserved GRBs regulate mostly developmental transcription factors, and the least conserved regulating cell adhesion molecules and neural developmental genes. Even shallowly conserved GRBs often have CNEs in all three lineages, arguing in favour of their ancient origin and divergence by turnover rather than lineage-specific emergence. Deeply and shallowly conserved GRBs also differ in the timing of their expression during development, their chromatin state and their repeat content. This suggest that GRB-like gene regulation of animal development has an ancient origin, and that the rate of regulatory region turnover within GRBs is influenced by the pleiotropy of the gene under regulation.