Ancient microRNA profiles of 14,300-yr-old canid samples confirm taxonomic origin and provide glimpses into tissue-specific gene regulation from the Pleistocene
- Bastian Fromm1,
- Marcel Tarbier1,
- Oliver Smith2,3,
- Emilio Mármol-Sánchez1,4,
- Love Dalén4,5,
- M. Tom P. Gilbert2,6 and
- Marc R. Friedländer1
- 1Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden
- 2Section for Evolutionary Genomics, The Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen, 1350 Copenhagen, Denmark
- 3Micropathology Ltd., Venture Centre, University of Warwick Science Park, Coventry CV4 7EZ, United Kingdom
- 4Centre for Palaeogenetics, 10691 Stockholm, Sweden
- 5Department of Bioinformatics and Genetics, Swedish Museum of Natural History, 10405 Stockholm, Sweden
- 6Norwegian University of Science and Technology, University Museum, 7012 Trondheim, Norway
- Corresponding authors: bastianfromm{at}gmail.com, marc.friedlander{at}scilifelab.se
Abstract
DNA sequencing is the current key technology for historic or ancient biological samples and has led to many exciting discoveries in the field of paleogenomics. However, functional insights into tissue identity, cellular composition, or gene regulation cannot be gained from DNA. Recent analyses have shown that, under favorable conditions, RNA can also be sequenced from ancient samples, enabling studies at the transcriptomic and regulatory level. Analyzing ancient RNA data from a Pleistocene canid, we find hundreds of intact microRNAs that are taxonomically informative, show tissue specificity and have functionally predictive characteristics. With an extraordinary age of 14,300 yr, these microRNA sequences are by far the oldest ever reported. The authenticity of the sequences is further supported by (i) the presence of canid/Caniformia-specific sequences that never evolved outside of this clade, (ii) tissue-specific expression patterns (cartilage, liver, and muscle) that resemble those of modern dogs, and (iii) RNA damage patterns that are clearly distinct from those of fresh samples. By performing computational microRNA-target enrichment analyses on the ancient sequences, we predict microRNA functions consistent with their tissue pattern of expression. For instance, we find a liver-specific microRNA that regulates carbohydrate metabolism and starvation responses in canids. In summary, we show that straightforward paleotranscriptomic microRNA analyses can give functional glimpses into tissue identity, cellular composition, and gene regulatory activity of ancient samples and biological processes that took place in the Pleistocene, thus holding great promise for deeper insights into gene regulation in extinct animals based on ancient RNA sequencing.
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Footnotes
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.078410.120.
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Freely available online through the RNA Open Access option.
- Received November 16, 2020.
- Accepted December 9, 2020.
This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
