South American Lungfish Has the Largest Animal Genome on Earth

The animal with the longest genome on Earth is neither a giant species nor an especially intelligent one. Instead, the record belongs to a wriggling freshwater creature that appears almost unchanged by time, poised at the evolutionary threshold between aquatic life and life on land.

Lungfish and their enormous genomes

That creature is the lungfish, a group of freshwater vertebrates whose unusual biology is matched by an immense genetic code. Lungfish can breathe both air and water, possess fins resembling limbs, and have a highly developed skeletal structure. These ancient-looking animals are believed to share a common ancestor with the four-limbed vertebrates known as tetrapods.

Understanding what is contained within such a vast genome could reveal how our own ancestors left watery environments and began walking on land. Scientists have now taken a major step by sequencing the largest lungfish genome: that of the South American lungfish, Lepidosiren paradoxa.

"With over 90 gigabases (in other words, 90 billion bases), the DNA of the South American species is the largest of all animal genomes and more than twice as large as the genome of the previous record holder, the Australian lungfish," says evolutionary biologist Axel Meyer of the University of Konstanz in Germany.

"Eighteen of the 19 chromosomes of the South American lungfish are each individually larger than the entire human genome with its almost 3 billion bases."

For context, this immense run of DNA bases is around 30 times longer than the human genome. Remarkably, however, the researchers identified only about 20,000 protein-coding sequences.

The African lungfish (Protopterus annectens), also sequenced by the team, had a comparable number of individual genes. Both species therefore have coding-gene totals broadly similar to those in the human genetic library, leaving researchers with a great deal of additional DNA whose role remains to be determined.

What lungfish DNA reveals about tetrapod evolution

The sequencing of these two lungfish follows related research on the Australian lungfish (Neoceratodus forsteri), which was published three years ago. Taken together, the sequences offer fresh evidence about how these fish diversified and evolved during the past 100 million years.

Lungfish take their name from the fact that, unlike other fish, they possess one or two lungs for breathing. This feature would have been crucial in making the transition to tetrapod life possible.

Only three lungfish lineages survive today: African, South American and Australian. Often described as living fossils, they can be compared to show how each lineage has changed since the first tetrapods appeared roughly 390 million years ago, although that timing remains debated. Such comparisons can illuminate one of the most important transformations in Earth’s evolutionary history, including the history of our own species.

Meyer, co-lead biochemist Manfred Schartl of the University of Würzburg in Germany, and their international colleagues found that the exceptional size of the Lepidosiren genome results from an abundance of ‘jumping genes’, also called transposable elements.

These mobile sequences are able to duplicate themselves and shift to new positions in the genome. Although they can be harmful to the organism carrying them, they may also drive rapid genetic change.

Work on another living fossil related to lungfish, the coelacanth, has indicated that transposons may have had a significant part in tetrapod evolution. Lepidosiren may help explain why: during the past 100 million years, its genome has expanded by the equivalent of an entire human genome every 10 million years.

The researchers concluded that this expansion is probably linked to very low levels of piRNA in lungfish. This form of RNA usually suppresses transposon activity, allowing the lungfish genome to balloon when that control is weak.

"And it continues to grow," Meyer says. "We have found evidence that the transposons responsible are still active."

South American lungfish chromosomes remain stable

Because these jumping genes remain highly active in Lepidosiren, the researchers expected its genome to be too challenging to analyse. Instead, they discovered that it is strikingly stable, with a relatively conservative gene arrangement that keeps the lungfish lean and mean.

This stability also allowed the team to reconstruct the chromosome architecture of ancestral lobe-finned fish. Their work extended beyond the three species examined to the ancestors of all tetrapods. The research confirmed this ancestry, providing a more complete set of tools for investigating our own evolutionary route.

The team also identified notable differences among the three living lungfish species. Australian lungfish have a single lung, can still breathe through their gills, and have retained the limb-like fins that once enabled movement onto land. African and South American lungfish, by contrast, have reduced gills and two lungs, while their limbs have evolved back into filament-like fins.

Experiments using mice edited to carry lungfish genes showed that this reversal in limb form was associated with changes to a signalling pathway called Shh, which directs embryonic development. Further findings are still expected.

"The genomes of all three lineages of lungfish, because of their crucial phylogenetic position, hold the key to a better understanding of how molecular and developmental processes and genomic evolutionary changes contributed to the conquest of land and the evolution of tetrapods, one of the main transitions during vertebrate evolution," the researchers write in their paper.

"The resource of chromosome-level genomes for all living lungfish lineages will now enable further research into lobe-finned ancestors of tetrapods who conquered land in the Devonian."

The research was published in Nature.