Sloth DNA Reveals How Jumping Genes Support Slow Metabolism

Sloths are remarkable animals: they are the world’s slowest-moving mammals, possess the slowest metabolisms, and do not continuously control their body temperature.

A fresh genetic investigation has now provided hints about how these notoriously leisurely creatures developed such an exceptionally low-energy way of life.

Sloth DNA and jumping genes

An international research group carried out an extensive study of the two-toed sloth (Choloepus didactylus), assessing its genome alongside those of dozens of mammals, including its fellow xenarthrans, anteaters and armadillos.

The researchers identified multiple DNA sequences able to relocate or reproduce themselves at new sites in the genome.

Called ‘transposons’ or ‘jumping genes’, these sequences are an important component of an animal’s evolutionary history.

For sloths and their evolutionary lineage, signs that these transposons have been moving through the genome extend back more than 30 million years.

What particularly interested the team, however, was that several of these genes were associated with mitochondria - the cell’s energy-producing structures - as well as other genes connected with metabolism.

"Our findings suggest that sloths might have evolved genetic 'backup systems' that help compensate for their 'relaxed mitochondria' and support their unique lifestyle," says biodiversity genomicist Camila Mazzoni, from the Leibniz Institute for Zoo and Wildlife Research in Germany.

Put another way, sloth cells’ modest energy requirements may have enabled mutations to build up in their slow-moving mitochondrial genomes.

The ‘jumping genes’ could offset this by establishing alternative genetic pathways that keep the animal functioning. Further research will be needed to establish whether this is the case.

Several of the genetic sequences identified in the study have, notably, been retained for roughly 30 million years. They seem to have emerged in a shared ancestor of present-day sloths, after the sloth lineage split from anteaters and armadillos.

"Sloths have the slowest metabolism of any mammal, yet they remain healthy," says Mazzoni.

"Understanding how they achieve this may reveal new insights into how cells manage energy efficiently."

Mitochondria, metabolism and human health

Supporting such an unhurried existence may be the principal advantage, while the study’s findings could also matter for human health.

"Many human conditions – including diabetes, aging-related disorders, neurodegeneration, and muscle wasting – involve problems with energy production and mitochondrial function," says molecular biologist Pedro Galante, from the Hospital Sírio Libanês in Brazil.

For instance, conditions including obesity can affect mitochondria, and disturbances in these cellular power stations have been associated with illnesses such as Parkinson’s.

The idea is that, if sloth DNA shows how a mammal can remain healthy while operating below full capacity, it might point towards ways to safeguard these energy-producing units in human cells.

"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," says Galante.

"In the long term, this could inform research into tissue preservation, critical care medicine, aging, metabolic disease, and even long-duration space travel."

The next steps for sloth genetic research

This work will nevertheless require a careful approach.

DNA changes introduced by jumping genes can cause illnesses including cancer in humans, which makes sloths’ apparently high tolerance of them all the more striking.

The researchers’ next task is to examine more closely the copy-and-paste genes retained by sloths for tens of millions of years, determining exactly what biological roles they perform - particularly in relation to mitochondria and metabolism.

These intriguing animals have developed traits that could otherwise seem disadvantageous - survival is generally thought to favour speed over slowness - and part of the reason can be traced directly to sloth DNA.

"Evolution has already run billions of experiments," says bioinformatician Marcela Uliano-Silva, from the Wellcome Sanger Institute in the UK.

"By studying unusual animals like sloths, we sometimes uncover biological solutions that humans never evolved."

The research was published in BMC Biology.