South American Lungfish Genome Is the Largest Animal Genome Ever Found

The longest genome in the animal kingdom does not belong to a giant animal or an especially intelligent creature. Instead, it belongs to a wriggling aquatic species that appears almost unchanged by time, poised at the evolutionary threshold of life on land.

Lungfish and the transition to land

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

Determining what this exceptionally long genome contains could reveal how our ancestors left watery environments and began moving on land. Scientists have now taken a major step forward 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."

In practical terms, this vast run of DNA bases is roughly 30 times longer than the human genome. Surprisingly, 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. This places the coding totals of both species in broadly the same range as our own genetic library, leaving a great deal of additional DNA whose role remains to be determined.

The sequencing of these two lungfish species builds on similar research into the Australian lungfish (Neoceratodus forsteri), published three years ago. Together, the sequences provide fresh insight into how these fish diversified and evolved across 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.

Three surviving lungfish lineages

Only three lungfish lineages still survive today: African, South American and Australian. Regarded as living fossils, they can be compared to examine the distinct ways each has changed since the earliest tetrapods emerged around 390 million years ago - although the precise date remains debated. This comparison can help explain a pivotal moment in the evolution of life on Earth, including that of our own species.

Meyer, co-lead biochemist Manfred Schartl of the University of Würzburg in Germany, and their international colleagues concluded that the immense size of the Lepidosiren genome results from its abundance of ‘jumping genes’, also known as transposable elements.

These disruptive sequences are able to replicate themselves and shift to new positions within a genome. Although they may harm the organism in which they occur, they can also drive rapid genetic change.

Research on another living fossil closely related to lungfish, the coelacanth, had indicated that transposons may have had a fairly important part in tetrapod evolution. Lepidosiren could help explain why. During the past 100 million years, its genome has increased by the equivalent of the entire human genome every 10 million years.

The researchers found that this is probably because lungfish have very low levels of piRNA, a form of RNA that usually suppresses transposon activity. As a result, their genome has simply expanded dramatically.

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

Jumping genes in the South American lungfish genome

Since the jumping genes remain active in Lepidosiren, the team expected its genome to be too difficult to analyse. Instead, they were surprised to discover that it is strikingly stable, with a relatively conservative gene arrangement that keeps the lungfish lean and mean.

This stability also allowed the scientists to reconstruct the chromosome architecture of ancestral lobe-finned fish, covering not only the three species examined but also the ancestors of every tetrapod. The study confirmed this ancestry and offers a more complete set of tools for investigating our own evolutionary history.

The team also catalogued notable differences among the three living species. Australian lungfish have only one lung, can still breathe using their gills, and retain the limb-like fins that once enabled movement onto land. African and South American lungfish have reduced gills and two lungs, while their limbs have evolved back into filament-like fins.

Using mice genetically edited to carry lungfish genes, the researchers showed that this reversal of limb development was linked to alterations in a signalling pathway called Shh, which directs embryonic development. Further discoveries are still to come.

"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 has been published in Nature.