Why are sloths slow? It's in their DNA

Why are sloths slow? It's in their DNA Lisa Lock Scientific Editor Robert Egan Associate Editor Sloths are the slowest mammals on the planet, but living in dense jungles has made them notoriously difficult to study. For the first time, scientists have now sequenced and analyzed the two-toed sloth genome and revealed the genetics behind its extremely slow metabolism. Building on work initiated at the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, Germany, researchers at the Wellcome Sanger Institute, IZW, Hospital Sírio Libanês in São Paulo, Brazil, and their collaborators sequenced and analyzed the genome of a captive two-toed sloth. By mapping its evolution, they discovered sloth-specific "jumping genes" that have been conserved over millions of years and are linked to its metabolism. The results, published in BMC Biology, begin to uncover the genetics behind the sloth's unique biology and could lead to new research into metabolism-associated conditions and aging in other mammals, including humans. How sloths evolved 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. 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 trees, where they hang motionless and camouflaged, and when they do move between branches to feed on leaves and fruit, 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, hovering around 5°C (41°F). Although they are slow, they are surprisingly strong swimmers, sometimes swimming long distances when searching for a mate. Sequencing the sloth genome To delve deeper into the unusual biology of sloths, IZW, Sanger Institute scientists and their collaborators turned to genomics. Using samples from a captive sloth, the team extracted DNA from tissues, which was then sequenced at the Max Planck Institute for Molecular Cell Biology and Genetics in Germany. Sanger Institute and IZW researchers then analyzed the sloth genome and compared the sequence with other mammal genomes, including those of an anteater and an armadillo, in a technique known as comparative genomics. This compares the genomes, or genetic "instruction manuals," of different mammals to understand what makes sloths unique. 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 chromosomes, which can lead to cancer in humans. Genes tied to metabolism By using genomics to look back through time and map the evolution of sloths, the researchers 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 "powerhouses" of cells that generate their energy—and metabolic pathways. Because sloths have one of the most unique metabolisms among mammals, the researchers believe these sloth-specific genes are related to their unusual adaptations to the environment and the evolution of their extremely slow metabolism. The next step is for the team to study these genes in more detail in cell lines, using lab experiments and single-cell sequencing to validate their function. They suggest that sloth cell lines could become a very good model for studying metabolism-associated and age-related health conditions in mammals, including humans. "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," says Dr. Marcela Uliano-Silva, senior bioinformatician and co-lead author at the Wellcome Sanger Institute. "Many human conditions—including diabetes, aging-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, aging, metabolic disease and even long-duration space travel," says Dr. Pedro Galante, co-lead author at Hospital Sírio Libanês in São Paulo, Brazil. "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," says Dr. Camila Mazzoni, co-lead author and head of evolutionary and conservation genomics at the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, Germany. Publication details Marcela Uliano-Silva et al, Elevated retrocopy burden and sloth-specific expansions illuminate mammalian genome evolution, BMC Biology (2026). DOI: 10.1186/s12915-026-02632-5 Journal information: BMC Biology Key concepts DNA sequencingbioenergeticsAdaptation, BiologicalBiological EvolutionBody Temperature RegulationEvolution, MolecularGenomesProvided by Wellcome Trust Sanger Institute