Circular RNA repertoires are associated with evolutionarily young transposable elements
- University of Lausanne, Switzerland
- Center for Molecular Biology of Heidelberg University, Germany
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).
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.
Download links
Further reading
-
- Evolutionary Biology
- Neuroscience
Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.
-
- Ecology
- Evolutionary Biology
Eurasia has undergone substantial tectonic, geological, and climatic changes throughout the Cenozoic, primarily associated with tectonic plate collisions and a global cooling trend. The evolution of present-day biodiversity unfolded in this dynamic environment, characterised by intricate interactions of abiotic factors. However, comprehensive, large-scale reconstructions illustrating the extent of these influences are lacking. We reconstructed the evolutionary history of the freshwater fish family Nemacheilidae across Eurasia and spanning most of the Cenozoic on the base of 471 specimens representing 279 species and 37 genera plus outgroup samples. Molecular phylogeny using six genes uncovered six major clades within the family, along with numerous unresolved taxonomic issues. Dating of cladogenetic events and ancestral range estimation traced the origin of Nemacheilidae to Indochina around 48 mya. Subsequently, one branch of Nemacheilidae colonised eastern, central, and northern Asia, as well as Europe, while another branch expanded into the Burmese region, the Indian subcontinent, the Near East, and northeast Africa. These expansions were facilitated by tectonic connections, favourable climatic conditions, and orogenic processes. Conversely, aridification emerged as the primary cause of extinction events. Our study marks the first comprehensive reconstruction of the evolution of Eurasian freshwater biodiversity on a continental scale and across deep geological time.
