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.
Sequencing data have been deposited in GEO under accession code GSE162152
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Suppl. Table 5. Human circRNA summary.Journal of Molecular and Cellular Cardiology, doi.org/10.1016/j.yjmcc.2016.07.007.
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The evolution of gene expression levels in mammalian organsNCBI Gene Expression Omnibus, GSE30352.
- Franziska Gruhl
- Peggy Janich
- Henrik Kaessmann
- Henrik Kaessmann
- David Gatfield
- David Gatfield
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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).
- Juan Valcárcel, Centre de Regulació Genòmica (CRG), Spain
- 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)
© 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.