Genome-Wide Analysis on Driver and Passenger RNA Editing Sites Suggests an Underestimation of Adaptive Signals in Insects

Adenosine-to-inosine (A-to-I) RNA editing leads to a similar effect to A-to-G mutations. RNA editing provides a temporo-spatial flexibility for organisms. Nonsynonymous (Nonsyn) RNA editing in insects is over-represented compared with synonymous (Syn) editing, suggesting adaptive signals of positive selection on Nonsyn editing during evolution. We utilized the brain RNA editome of Drosophila melanogaster to systematically study the LD (r2) between editing sites and infer its impact on the adaptive signals of RNA editing. Pairs of editing sites (PESs) were identified from the transcriptome. For CDS PESs of two consecutive editing sites, their occurrence was significantly biased to type-3 PES (Syn-Nonsyn). The haplotype frequency of type-3 PES exhibited a significantly higher abundance of AG than GA, indicating that the rear Nonsyn site is the driver that promotes the editing of the front Syn site (passenger). The exclusion of passenger Syn sites dramatically amplifies the adaptive signal of Nonsyn RNA editing. Our study for the first time quantitatively demonstrates that the linkage between RNA editing events comes from hitchhiking effects and leads to the underestimation of adaptive signals for Nonsyn editing. Our work provides novel insights for studying the evolutionary significance of RNA editing events

The Many Roles of A-to-I RNA Editing in Animals: Functional or Adaptive?

Metazoan adenosine-to-inosine (A-to-I) RNA editing is a highly conserved mechanism that diversifies the transcriptome by post-transcriptionally converting adenosine to inosine. Millions of editing sites have been identified in different species and, based on abnormal editing observed in various disorders, it is intuitive to conclude that RNA editing is both functional and adaptive. In this review, we propose the following major points: (1) “Function/functional” only represents a molecular/phenotypic consequence and is not necessarily connected to “adaptation/adaptive”; (2) Adaptive editing should be judged in the light of evolution and emphasize advantages of temporal-spatial flexibility; (3) Adaptive editing could, in theory, be extended from nonsynonymous sites to all potentially functional sites. This review seeks to conceptually bridge the gap between molecular biology and evolutionary biology and provide a more objective understanding on the biological functions and evolutionary significance of RNA editing

Differential adaptive RNA editing signals between insects and plants revealed by a new measurement termed haplotype diversity

Abstract Background C-to-U RNA editing in plants is believed to confer its evolutionary adaptiveness by reversing unfavorable DNA mutations. This “restorative hypothesis” has not yet been tested genome-wide. In contrast, A-to-I RNA editing in insects like Drosophila and honeybee is already known to benefit the host by increasing proteomic diversity in a spatial-temporal manner (namely “diversifying hypothesis”). Methods We profiled the RNA editomes of multiple tissues of Arabidopsis thaliana, Drosophila melanogaster, and Apis melifera. We unprecedentedly defined the haplotype diversity (HD) of RNA molecules based on nonsynonymous editing events (recoding sites). Results Signals of adaptation is confirmed in Arabidopsis by observing higher frequencies and levels at nonsynonymous editing sites over synonymous sites. Compared to A-to-I recoding sites in Drosophila, the C-to-U recoding sites in Arabidopsis show significantly lower HD, presumably due to the stronger linkage between C-to-U events. Conclusions C-to-U RNA editing in Arabidopsis is adaptive but it is not designed for diversifying the proteome like A-to-I editing in Drosophila. Instead, C-to-U recoding sites resemble DNA mutations. Our observation supports the restorative hypothesis of plant C-to-U editing which claims that editing is used for fixing unfavorable genomic sequences

The evolutionary arms race between transposable elements and piRNAs in Drosophila melanogaster

Abstract Background The piwi-interacting RNAs (piRNAs) are small non-coding RNAs that specifically repress transposable elements (TEs) in the germline of Drosophila. Despite our expanding understanding of TE:piRNA interaction, whether there is an evolutionary arms race between TEs and piRNAs was unclear. Results Here, we studied the population genomics of TEs and piRNAs in the worldwide strains of D. melanogaster. By conducting a correlation analysis between TE contents and the abundance of piRNAs from ovaries of representative strains of D. melanogaster, we find positive correlations between TEs and piRNAs in six TE families. Our simulations further highlight that TE activities and the strength of purifying selection against TEs are important factors shaping the interactions between TEs and piRNAs. Our studies also suggest that the de novo generation of piRNAs is an important mechanism to repress the newly invaded TEs. Conclusions Our results revealed the existence of an evolutionary arms race between the copy numbers of TEs and the abundance of antisense piRNAs at the population level. Although the interactions between TEs and piRNAs are complex and many factors should be considered to impact their interaction dynamics, our results suggest the emergence, repression specificity and strength of piRNAs on TEs should be considered in studying the landscapes of TE insertions in Drosophila. These results deepen our understanding of the interactions between piRNAs and TEs, and also provide novel insights into the nature of genomic conflicts of other forms

Full-Length Transcriptome Profiling of <i>Coridius chinensis</i> Mitochondrial Genome Reveals the Transcription of Genes with Ancestral Arrangement in Insects

Coridius chinensis (Hemiptera: Dinidoridae) is a medicinal insect. Its mitochondrial gene arrangement is consistent with that of Drosophila melanogaster and Erthesina fullo, the two insects with well-studied mitochondrial transcription. To investigate whether the structural consistency of mitochondrial genes leads to similarities in transcription and post-transcriptional processing, we improved the gene annotation and constructed a quantitative transcription map for the C. chinensis mitochondrial genome (mitogenome) using full-length transcriptome sequencing. The size of this mitogenome was 16,214 bp and the proposed model of mitochondrial transcription was similar to that of Drosophila. Both strands were nearly entirely transcribed except for the antisense genes downstream of trnS2 on N strand. The expression of cytochrome c subunit genes is higher than that of NADH-dehydrogenase subunit genes. The post-transcriptional cleavage process followed the “tRNA punctuation” model, and both the “reverse cleavage” model in Drosophila and “forward cleavage” model in E. fullo were found in C. chinensis. In addition, we found that long non-coding RNAs from the control region contained tandem repeats. Polyadenylation was performed after CCA triplet at the 3′ end of tRNA. The isoform diversity of lrRNA was identified. Our study sheds light on the transcriptional regulation and RNA processing of insect mitogenomes with the putative ancestral gene arrangement

Adaptation of A-to-I RNA editing in <i>Drosophila</i>

<div><p>Adenosine-to-inosine (A-to-I) editing is hypothesized to facilitate adaptive evolution by expanding proteomic diversity through an epigenetic approach. However, it is challenging to provide evidences to support this hypothesis at the whole editome level. In this study, we systematically characterized 2,114 A-to-I RNA editing sites in female and male brains of <i>D</i>. <i>melanogaster</i>, and nearly half of these sites had events evolutionarily conserved across <i>Drosophila</i> species. We detected strong signatures of positive selection on the nonsynonymous editing sites in <i>Drosophila</i> brains, and the beneficial editing sites were significantly enriched in genes related to chemical and electrical neurotransmission. The signal of adaptation was even more pronounced for the editing sites located in X chromosome or for those commonly observed across <i>Drosophila</i> species. We identified a set of gene candidates (termed “PSEB” genes) that had nonsynonymous editing events favored by natural selection. We presented evidence that editing preferentially increased mutation sequence space of evolutionarily conserved genes, which supported the adaptive evolution hypothesis of editing. We found prevalent nonsynonymous editing sites that were favored by natural selection in female and male adults from five strains of <i>D</i>. <i>melanogaster</i>. We showed that temperature played a more important role than gender effect in shaping the editing levels, although the effect of temperature is relatively weaker compared to that of species effect. We also explored the relevant factors that shape the selective patterns of the global editomes. Altogether we demonstrated that abundant nonsynonymous editing sites in <i>Drosophila</i> brains were adaptive and maintained by natural selection during evolution. Our results shed new light on the evolutionary principles and functional consequences of RNA editing.</p></div

The editing sites with events observed in brain of <i>D</i>. <i>simulans</i> and the matched brain sample of <i>D</i>. <i>melanogaster</i>.

<p>The editing sites with events observed in brain of <i>D</i>. <i>simulans</i> and the matched brain sample of <i>D</i>. <i>melanogaster</i>.</p

The editing sites detected in female and male adults in five strains of <i>D</i>. <i>melanogaster</i>.

<p>The editing sites detected in female and male adults in five strains of <i>D</i>. <i>melanogaster</i>.</p

Additional file 1 of Differential adaptive RNA editing signals between insects and plants revealed by a new measurement termed haplotype diversity

Supplementary Material