PhD defence: Pei Zhang

On the Origin and Evolution of RNA Editing in Metazoans

Supervisor
Professor Guojie Zhang, Section for Ecology and Evolution, UCPH

Examiners
Anders Albrechtsen (Chair), Wen Wang, and Xin Zhou

Abstract
A-to-I editing is the most prevalent editing type in metazoan, and diversifies the transcriptome by altering selected adenosines to inosines in RNA molecules. Given inosine is recognized as guanosine by biological machines in vovo, A-to-I editing plays important roles in numerous biochemical processes. Recent advances have revealed the important biological implications of A-to-I editing, including modulating neural system, regulating immune process, contributing to environmental adaptation. But until now, systematically investigations on A-to-I editing are still limited to a handle of metazoan lineages. I profiled of editomes in 22 species that encompass all the key transitions in metazoan evolution. First, I designed a strategy to identify reliable RNA editing sites for non-model species of which the individuals always harbor high levels of genetic heterozygosity and are generally genetic distinct from the strains or individuals used to assemble genome references. Then, comparative analyses of editomes reveal the origin, prevalence, distribution, evolution and adaptive potential of A-to-I editing in metazoan. Analyses in this thesis present the first direct evidence that extensive A-to-I editing of nuclear-transcribed RNAs originated in the last common ancestor of extant metazoans, following its divergence from unicellular choanoflagellates. Since then, the nucleotide sequence features surrounding the A-to-I editing sites have been under strong evolutionary constraint in most animal phyla, which is tightly associated with editing level of A-to-I sites. Analyses in this thesis also demonstrated that recoding editing of protein-coding sequences is generally rare and nonadaptive in metazoans, except in Drosophila and cephalopods. More importantly, the extensive survey across the phylogeny of metazoans uncovered for the first time that, in addition to regulating neurological functions, RNA editing prefers to target on cytoskeleton-related genes in diverse lineages, emphasizing an important, but previously unappreciated, role of RNA editing in regulating cytoskeleton-related functions in metazoans.