Largest animal genome ever gives new insight into tetrapods’ ancestor

The South American lungfish (Lepidosiren paradoxa) has the largest animal genome ever sequenced, according to a new Nature paper.

“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 biologist Axel Meyer of the University of Konstanz, Germany, who co-led the research.

“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.”

Illustration of a lungfish against a black background. It is a warm brown, eel-like fish with small fins
South American lungfish (Lepidosiren paradoxa). Credit: © Katherine Seghers, Louisiana State University

If you were to picture a double-helix DNA molecule as a twisting ladder, a nucleotide base pair would be a single rung in that ladder. This is what encodes the genetic information.

The researchers found that “autonomous transposons” are responsible for the South American lungfish’s enormous genome. Also known as “jumping genes”, these are DNA sequences that can copy and paste themselves throughout the genome and causing it to expand.

The new analysis shows that the expansion rate of the South American lungfish genome is the fastest ever seen – growing by the size of the entire human genome every 10 million years.

This has happened, in part, due to very low amounts of PIWI-interacting RNAs (piRNAs). These are a class of RNA that control the copy number and activity of transposons, and therefore control genome size.

According to Meyer, the South American lungfish’s genome continues to grow today: “We have found evidence that the transposons responsible are still active.”

Lungfishes are named for their ability to breathe air using their lung or lungs. There are 6 known species living today in Africa, South America, and Australia. The African lungfish (Protopterus annecten) was also sequenced in this study.

Illustration of a lungfish against a black background. It is a brown, eel-like fish with small fins
South American lungfish (Lepidosiren paradoxa). Credit: © Katherine Seghers, Louisiana State University

As Sarcopterygii (lobe-finned fishes), lungfish are more closely related to tetrapods – modern day amphibians, reptiles, birds, and mammals – than to other fishes.

This is because the ancestor of all tetrapods was a lobe-finned fish. In the Devonian period, some 420 to 360 million years ago, it would have used its powerful pectoral fins to pull itself out of the water and onto land.

“Tetrapod ancestors conquered land with limbs that evolved from fins and were breathing air through lungs,” the authors write in the paper.

“These features probably predated the colonisation of land. Only by studying the biology of the surviving lungfish lineages can we investigate the genomic basis and molecular-developmental mechanisms that facilitated the water–land transition of vertebrates.”

Australian lungfish still retain these limb-like fins, but African and South American species’ have simplified back into filamentous fins over the last 100 million years or so.

“In our research, we also used experiments with CRISPR-Cas transgenic mice to show that this simplification of the fins is attributable to a change in what is known as the sonic hedgehog (Shh)-signalling pathway,” says Meyer.

The team’s resource of chromosome-level genomes for all living lungfish lineages will allow further research into lobe-finned ancestors of tetrapods.

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