Sloths are the slowest mammals on Earth, and their dense jungle habitat has made them notoriously difficult to study. Now, for the first time, scientists have sequenced and analyzed the two-toed sloth genome, uncovering the genetics behind their exceptionally slow metabolism. The results were published in BMC Biology.
The work was led by researchers at the Wellcome Sanger Institute, the Leibniz Institute for Zoo and Wildlife Research (IZW), and Hospital Sírio Libanês, building on work initiated at IZW. Using DNA extracted from the tissues of a captive two-toed sloth—sequenced at the Max-Planck Institute for Molecular Cell Biology & Genetics—the team compared the sloth genome to those of related mammals, including anteaters and armadillos, through comparative genomics.
Sloths belong to Xenarthra, the only clade of placental mammals to have originated in South America, a group that has existed for 65.5 million years. Modern sloths spend most of their time hanging motionless in trees, feeding on leaves and fruit at a slow pace. Their metabolism is often less than half of what would be expected for their body size, and to conserve energy they can switch between regulating their own body temperature and allowing it to fluctuate with the environment.
The scientists found that the sloth genome contains several copies of active transposable elements—known as transposons or "jumping genes"—DNA sequences that can copy and paste themselves to new positions in the genome. In humans, transposons are typically inactive, old, and fragmented; active ones can cause chromosomal rearrangements linked to cancer. In sloths, these elements are still active and have been conserved since arising in the last common ancestor of all surviving sloth species approximately 30 million years ago.
Notably, many of these genes are connected to mitochondria and to metabolic pathways. The researchers believe these sloth-specific genes are related to the evolution of the animal's unusual metabolism.
“Evolution has already run billions of experiments,” said Marcela Uliano-Silva, co-lead author of the study. “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.”
The team's next step is to study these genes in cell lines using lab experiments and single-cell sequencing to validate their function. Sloth cell lines, the researchers suggest, may offer a useful model for studying metabolism-associated and age-related conditions in mammals.
“Many human conditions—including diabetes, ageing-related disorders, neurodegeneration, and muscle wasting—involve problems with energy production and mitochondrial function,” said co-lead Pedro Galante. “In the long term, this could inform research into tissue preservation, critical care medicine, ageing, metabolic disease, and even long-duration space travel.”
The work was led by researchers at the Wellcome Sanger Institute, the Leibniz Institute for Zoo and Wildlife Research (IZW), and Hospital Sírio Libanês, building on work initiated at IZW. Using DNA extracted from the tissues of a captive two-toed sloth—sequenced at the Max-Planck Institute for Molecular Cell Biology & Genetics—the team compared the sloth genome to those of related mammals, including anteaters and armadillos, through comparative genomics.
Sloths belong to Xenarthra, the only clade of placental mammals to have originated in South America, a group that has existed for 65.5 million years. Modern sloths spend most of their time hanging motionless in trees, feeding on leaves and fruit at a slow pace. Their metabolism is often less than half of what would be expected for their body size, and to conserve energy they can switch between regulating their own body temperature and allowing it to fluctuate with the environment.
The scientists found that the sloth genome contains several copies of active transposable elements—known as transposons or "jumping genes"—DNA sequences that can copy and paste themselves to new positions in the genome. In humans, transposons are typically inactive, old, and fragmented; active ones can cause chromosomal rearrangements linked to cancer. In sloths, these elements are still active and have been conserved since arising in the last common ancestor of all surviving sloth species approximately 30 million years ago.
Notably, many of these genes are connected to mitochondria and to metabolic pathways. The researchers believe these sloth-specific genes are related to the evolution of the animal's unusual metabolism.
“Evolution has already run billions of experiments,” said Marcela Uliano-Silva, co-lead author of the study. “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.”
The team's next step is to study these genes in cell lines using lab experiments and single-cell sequencing to validate their function. Sloth cell lines, the researchers suggest, may offer a useful model for studying metabolism-associated and age-related conditions in mammals.
“Many human conditions—including diabetes, ageing-related disorders, neurodegeneration, and muscle wasting—involve problems with energy production and mitochondrial function,” said co-lead Pedro Galante. “In the long term, this could inform research into tissue preservation, critical care medicine, ageing, metabolic disease, and even long-duration space travel.”