Milestone as RNA recovered from Tasmanian tiger specimen

Swedish researchers have successfully isolated and sequenced century-old RNA molecules from a Tasmanian tiger specimen preserved at room temperature in a museum collection, resulting in the reconstruction of skin and skeletal muscle transcriptomes from an extinct species for the first time. Writing in the journal Genome Research, the researchers noted that their findings have relevant implications for international efforts to resurrect extinct species, as well as for studying pandemic RNA viruses.

The Tasmanian tiger, also known as the thylacine, was once widespread in Australia but had been confined to Tasmania by the time Europeans arrived in the 18th century. The species’ ultimate demise came about when it was declared as an agricultural pest and a bounty of £1 per each full-grown animal killed was set by 1888. The last known living thylacine died in captivity in 1936 at the Beaumaris Zoo in Hobart.

Recent efforts in de-extinction have focused on the thylacine, as its natural habitat in Tasmania is still mostly preserved, and its reintroduction could help recovering past ecosystem equilibriums lost after its final disappearance. However, reconstructing a functional living thylacine not only requires a comprehensive knowledge of its genome (DNA) but also of tissue-specific gene expression dynamics and how gene regulation worked, which are only attainable by studying its transcriptome (RNA).

“Resurrecting the Tasmanian tiger or the woolly mammoth is not a trivial task and will require a deep knowledge of both the genome and transcriptome regulation of such renowned species, something that only now is starting to be revealed,” said Emilio Mármol, the lead author of the new study, which was conducted by researchers at SciLifeLab in collaboration with the Centre for Palaeogenetics — a joint venture between the Swedish Museum of Natural History and Stockholm University.

The researchers behind the study sequenced the transcriptome of the skin and skeletal muscle tissues from a 130-year-old desiccated thylacine specimen preserved at room temperature in the Swedish Museum of Natural History, which led to the identification of tissue-specific gene expression signatures that resemble those from living extant marsupial and placental mammals. The recovered transcriptomes were of such good quality that it was possible to identify muscle- and skin-specific protein coding RNAs, and led to the annotation of missing ribosomal RNA and microRNA genes — the latter following MirGeneDB recommendations.

“This is the first time that we have had a glimpse into the existence of thylacine-specific regulatory genes, such as microRNAs, that got extinct more than one century ago,” said Marc R Friedländer, an associate professor at Stockholm University and SciLifeLab.

This pioneering study opens up exciting opportunities and implications for exploring the vast collections of specimens and tissues stored at museums across the globe, where RNA molecules might await to be uncovered and sequenced. Love Dalén, a professor at Stockholm University and the Centre for Palaeogenetics, concluded, “In the future, we may be able to recover RNA not only from extinct animals, but also RNA virus genomes such as SARS-CoV-2 and their evolutionary precursors from the skins of bats and other host organisms held in museum collections.”

Image caption: Tasmanian tiger specimen used in the study and preserved in desiccation at room temperature in the Swedish National History Museum. Image credit: Emilio Mármol Sánchez (photograph) and Panagiotis Kalogeropoulos (editing).