Fig. 6. Species-specific dsRNA structures contribute to the formation of novel RNA editing sites.

a Several hominid-specific exonic RNA editing sites were introduced to the Asns gene following a single G-to-A genomic substitution modifying the RNA secondary structure. Two uppermost sequences show a few CDS adenosines being edited in human and chimpanzee. These editing events are not conserved in more distant primates. In non-hominid primates (two lowermost structures), the RNA structure is very similar, except for a single hominid-specific mismatch (internal loop) feature, resulting from a genomic G-to-A substitution in the intronic ECS of hominids. b The extensive editing in NEIL1 CDS seen in primates (top) is conserved in some non-primates as well (bottom). However, editing is much weaker in rodents (middle). Mutations in the rat sequence alter the secondary structure, while the sheep structure is more similar to the human one. c The emergence of human-specific RNA-editing site. A human-specific G-to-A substitution results in an A:C mismatch within a dsRNA structure already present in the ancestral hominid. This newly introduced adenosine is efficiently deaminated by the ADAR enzymes, and an additional weaker site appears in the complementary sequence. In each of the three panels, the top track shows the locus of the edited CDS region and the ECS (gray dashed-line boxes) within the corresponding gene (blue boxes – exons; lines with arrowheads – introns); the bottom track shows the corresponding calculated secondary structures. The topology of the phylogenetic tree for the species presented is shown on the left (branch lengths not to scale). Species names are denoted on the right. Major structure alternations along with indels and single nucleotide substitutions (relative to human) are indicated. Adenosines in all structures are annotated in different colors based on their calculated RNA editing levels (pooling all brain samples available, per species; Gray – no detectable editing, blue – low editing levels; red – high editing levels). Editing levels were not assessed for sites covered by <50 reads.