Sloths are the slowest mammals on the planet, and living in dense jungles has made them difficult to study. For the first time, scientists have now sequenced and analysed the two-toed sloth genome and revealed the genetics behind their extremely slow metabolism. By mapping their evolution, the international team discovered sloth-specific ‘jumping genes’ that have been conserved over millions of years and are linked to the metabolism. The results, published in the journal BMC Biology, reveal insights into the genetics behind the sloth’s unique biology. This could pave the way for further research into metabolism-related conditions and ageing in other mammals, including humans.
Building on work initiated at the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), scientists from the Wellcome Sanger Institute, Leibniz IZW, Hospital Sírio Libanês in São Paulo (Brazil), and their collaborators sequenced and analysed the genome of a captive Linnaeus's two-toed sloth (Choloepus didactylus). The team extracted DNA from tissue samples taken from the sloth, which was then sequenced at the Max Planck Institute for Molecular Cell Biology and Genetics in Germany. The team then analysed the sloth genome and compared the sequence to other mammal genomes, including an anteater and an armadillo, in a technique known as comparative genomics.
The scientists found that the sloth genome had several copies of active transposable elements, called ‘transposons’ or ‘jumping genes’, which are DNA sequences that can copy and paste themselves to change their position in the genome. Some transposons are still seen in the human genome, but are usually inactive, old and fragmented. Active transposable elements, however, create rearrangements in the chromosomes, which can lead to cancer in humans.
By using genomics to look back through time and map the evolution of sloths, the scientists also found these ‘jumping genes’ arose in the last common ancestor of all extant sloth species, around 30 million years ago. The genes have since been conserved over time, making them ingrained genetic sequences that are unique to sloths. The team was surprised to find that many of these genes are connected to mitochondria – the ‘power houses’ of cells that generate their energy – and metabolic pathways. Since sloths have one of the most unique metabolisms among mammals, the scientists believe that these sloth-specific genes are related to their unusual adaptations to the environment and evolution of their extremely slow metabolism.
Unique adaptations in the only placental mammals that originated in South America
Along with armadillos and anteaters, sloths are members of Xenarthra, the only clade of placental mammals to have originated in South America. Xenarthrans have been around for 65.5 million years, with extinct sloth ancestors including elephant-sized giant ground sloths. Now, modern-day sloths are all tree-dwelling and belong to two groups – two-toed sloths and three-toed sloths.
Sloths are the slowest of all mammals. They spend most of their time in the trees where they hang motionless and camouflaged, and when they do move between branches to feed on leaves and fruits – it all happens at a slow pace. Sloths have the lowest metabolism among mammals, often less than half of what is expected for their body size. To conserve energy, they can switch between self-regulating their body temperature, and allowing it to fluctuate with the environment. While being slow, they are strong swimmers, sometimes covering large distances in water when searching for a mate.
Opening the door for studying metabolism- and age-related health conditions in mammals
To gain a deeper understanding of the unusual biology of sloths, the team of scientists and their collaborators turned to genomics. The next step is to study these genes in more detail using cell lines, lab experiments and single-cell sequencing to validate their function. The team suggests that sloth cell lines could be an excellent model for studying metabolism- and age-related health conditions in mammals, including humans.
Dr Marcela Uliano-Silva, Senior Bioinformatician and co-lead author at the Wellcome Sanger Institute, said: “Evolution has already run billions of experiments. By studying unusual animals like sloths, we sometimes uncover biological solutions that humans never evolved. Using genomics to look back through time, we found ‘jumping genes’ that sloths have conserved over millions of years. These sloth-specific genes are linked to mitochondria and metabolic pathways, suggesting they might be related to the evolution of their extremely slow metabolism.”
Dr Pedro Galante, co-lead author at the Hospital Sírio Libanês in São Paulo, Brazil, said: “Many human conditions – including diabetes, ageing-related disorders, neurodegeneration, and muscle wasting – involve problems with energy production and mitochondrial function. While further research is needed, sloth cell lines may offer a natural model for understanding how organisms cope with low-energy states, and what goes wrong in disease. In the long term, this could inform research into tissue preservation, critical care medicine, ageing, metabolic disease, and even long-duration space travel.”
Dr Camila Mazzoni, co-lead author and Head of Evolutionary and Conservation Genomics at the Leibniz-IZW in Berlin, Germany, said: “Sloths have the slowest metabolism of any mammal, yet they remain healthy. Understanding how they achieve this may reveal new insights into how cells manage energy efficiently. Our findings suggest that sloths might have evolved genetic ‘backup systems’ that help compensate for their ‘relaxed mitochondria’ and support their unique lifestyle.”
This research was supported by Wellcome, the European Union’s Horizon 2020 research and innovation programme and the São Paulo Research Foundation.