Circular RNA repertoires are associated with evolutionarily young transposable elements
Abstract
Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution - as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.
Data availability
Sequencing data have been deposited in GEO under accession code GSE162152
-
Suppl. Table 4. Mouse circRNA summary.Journal of Molecular and Cellular Cardiology, doi.org/10.1016/j.yjmcc.2016.07.007.
-
Suppl. Table 5. Human circRNA summary.Journal of Molecular and Cellular Cardiology, doi.org/10.1016/j.yjmcc.2016.07.007.
-
DNA replication time of the human genome G1 phase.Sequence Read Archive, SRA052697.
-
Suppl. Table S2. Haploinsufficiency predictions without study bias.Nucleic Acids Research, https://doi.org/10.1093/nar/gkv474.
-
The evolution of gene expression levels in mammalian organsNCBI Gene Expression Omnibus, GSE30352.
Article and author information
Author details
Funding
Swiss Institute of Bioinformatics (SIB PhD Fellowship)
- Franziska Gruhl
Human Frontiers Science Program (LT000158/2013-L)
- Peggy Janich
European Research Council (242597,SexGenTransEvolution)
- Henrik Kaessmann
European Research Council (615253,OntoTransEvol)
- Henrik Kaessmann
Swiss National Science Foundation (NCCR RNA & Disease (141735,182880))
- David Gatfield
Swiss National Science Foundation (individual grant 179190)
- David Gatfield
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mouse samples were collected by the Kaessmann lab at the Center for Integrative Genomics in Lausanne. Rat samples were kindly provided by Carmen Sandi, EPFL, Lausanne. Opossum samples were kindly provided by Peter Giere, Museum für Naturkunde, Berlin. All animal procedures were performed in compliance with national and international ethical guidelines and regulations for the care and use of laboratory animals and were approved by the local animal welfare authorities (Vaud Cantonal Veterinary office, Berlin State Office of Health and Social Affairs). The rhesus macaque samples were provided by the Suzhou Experimental Animal Center (China); the Biomedical Research Ethics Committee of Shanghai Institutes for Biological Sciences reviewed the use and care of the animals in the research project (approval ID: ER-SIBS-260802P). All rhesus macaques used in this study suffered sudden deaths for reasons other than their participation in this study and without any relation to the organ sampled. The use of all samples for the work described in this study was approved by an ERC Ethics Screening panel (associated with H.K.'s ERC Consolidator Grant 615253, OntoTransEvol).
Human subjects: The human post-mortem samples were provided by the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland (USA). They originated from individuals with diverse causes of death that, given the information available, were not associated with the organ sampled. Written consent for the use of human tissues for research was obtained from all donors or their next of kin by this tissue bank. The use of these samples was approved by an ERC Ethics Screening panel (associated with H.K.'s ERC Consolidator Grant 615253, OntoTransEvol), and, in addition, by the local ethics committee in Lausanne (authorization 504/12).
Reviewing Editor
- Juan Valcárcel, Centre de Regulació Genòmica (CRG), Spain
Version history
- Preprint posted: March 1, 2021 (view preprint)
- Received: March 1, 2021
- Accepted: September 19, 2021
- Accepted Manuscript published: September 20, 2021 (version 1)
- Accepted Manuscript updated: September 22, 2021 (version 2)
- Accepted Manuscript updated: September 28, 2021 (version 3)
- Version of Record published: October 14, 2021 (version 4)
Copyright
© 2021, Gruhl et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,341
- Page views
-
- 316
- Downloads
-
- 9
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Evolutionary Biology
Changes in an organism’s environment, genome, or gene expression patterns can lead to changes in its metabolism. The metabolic phenotype can be under selection and contributes to adaptation. However, the networked and convoluted nature of an organism’s metabolism makes relating mutations, metabolic changes, and effects on fitness challenging. To overcome this challenge, we use the long-term evolution experiment (LTEE) with E. coli as a model to understand how mutations can eventually affect metabolism and perhaps fitness. We used mass spectrometry to broadly survey the metabolomes of the ancestral strains and all 12 evolved lines. We combined this metabolic data with mutation and expression data to suggest how mutations that alter specific reaction pathways, such as the biosynthesis of nicotinamide adenine dinucleotide, might increase fitness in the system. Our work provides a better understanding of how mutations might affect fitness through the metabolic changes in the LTEE and thus provides a major step in developing a complete genotype–phenotype map for this experimental system.
-
- Ecology
- Evolutionary Biology
Temperature determines the geographical distribution of organisms and affects the outbreak and damage of pests. Insects seasonal polyphenism is a successful strategy adopted by some species to adapt the changeable external environment. Cacopsylla chinensis (Yang & Li) showed two seasonal morphotypes, summer-form and winter-form, with significant differences in morphological characteristics. Low temperature is the key environmental factor to induce its transition from summer-form to winter-form. However, the detailed molecular mechanism remains unknown. Here, we firstly confirmed that low temperature of 10 °C induced the transition from summer-form to winter-form by affecting the cuticle thickness and chitin content. Subsequently, we demonstrated that CcTRPM functions as a temperature receptor to regulate this transition. In addition, miR-252 was identified to mediate the expression of CcTRPM to involve in this morphological transition. Finally, we found CcTre1 and CcCHS1, two rate-limiting enzymes of insect chitin biosyntheis, act as the critical down-stream signal of CcTRPM in mediating this behavioral transition. Taken together, our results revealed that a signal transduction cascade mediates the seasonal polyphenism in C. chinensis. These findings not only lay a solid foundation for fully clarifying the ecological adaptation mechanism of C. chinensis outbreak, but also broaden our understanding about insect polymorphism.