Scientists have successfully sequenced the largest genome found in the animal kingdom, which belongs to the lungfish. This research provides insights into how fish ancestors of modern terrestrial vertebrates managed to adapt to life on land.
This genome is thirty times larger than that of humans: An international group of researchers, spearheaded by evolutionary biologist Axel Meyer from Konstanz and biochemist Manfred Schartl from Würzburg, has sequenced the lungfish genome, the largest known among animals. Their findings shed light on how the fish ancestors of today’s land vertebrates transitioned to life on land.
Let us take a journey back to the Devonian era, which spanned 420 to 360 million years ago. In a shallow zone near the water, a momentous event took place: a lobe-finned fish crawled onto land using its sturdy pectoral fins, gliding its body over the muddy shore. This fish was in no hurry to return to the water, as it possessed lungs, much like the land-dwelling vertebrates of today.
Such a scenario may represent one of the earliest instances of a vertebrate making its way onto land, marking a pivotal moment in evolutionary history. All subsequent land vertebrates, commonly known as tetrapods—including amphibians, reptiles, birds, and mammals, including humans—can trace their lineage back to this aquatic ancestor. However, one question still lingers: What enabled the lobe-finned fish to be so well-equipped to transition to terrestrial life?
An examination of its living relatives
To answer this longstanding question, scientists analyzed the genetic material of the lungfish, the closest living relatives of our ancient Devonian ancestor. There are currently three lineages of lungfish: one in Africa, one in South America, and one in Australia. These ancient “living fossils” appear to have undergone little change over time, resembling their ancestors closely. Since DNA, our genetic material, consists of nucleobases and the arrangement of these bases encodes genetic information, a comparative analysis of lungfish genomes was only feasible with access to their complete sequences.
While it was previously known that lungfish possess large genomes, the full scope of their enormity and the implications of this were not understood until now. Sequencing these genomes was a complex task, requiring significant effort from both technical and bioinformatics perspectives. Nonetheless, Axel Meyer and Manfred Schartl’s international team successfully sequenced the genome of the South American lungfish as well as one from the African lineage. The previously largest genome sequence of the Australian lungfish (Neoceratodus) had already been accomplished by the same researchers. Their findings were published in the journal Nature.
Truly massive, but why?
Specifically, the genetic material of the South American lungfish shatters all records for size. “With over 90 gigabases—90 billion bases—the DNA of this species is the largest genome among animals, more than twice the size of the previous record holder, the Australian lungfish. Notably, 18 of the 19 chromosomes of the South American lungfish are each individually larger than the entire human genome, which has nearly 3 billion bases,” states Meyer. The expansion of the lungfish genome over time can primarily be attributed to autonomous transposons, which are DNA sequences that replicate themselves and change their location within the genome, leading to growth.
Though this phenomenon is observed in other organisms as well, the team’s analyses revealed that the South American lungfish’s genome expansion rate is unprecedented: Its genome has grown by an amount equivalent to the entire human genome approximately every 10 million years. “And it continues to grow,” Meyer notes, adding that they found indications that the active transposons are still functioning. The researchers identified that this incredible genome growth is, at least in part, due to a very low abundance of piRNA, a type of RNA involved in silencing transposons.
Yet surprisingly stable
While transposons can replicate and shift around within the genome, influencing its growth, this process can also significantly alter the genetic material of an organism and create instability. Surprisingly, the study found no correlation between the high number of transposons and genome instability; instead, the lungfish genome shows remarkable stability, with a relatively conservative arrangement of genes. This stability allowed the research team to reconstruct the chromosomal architecture (karyotype) of the ancestral tetrapod based on the sequences of currently living lungfish species.
Moreover, comparing the lungfish genomes provided insights into the genetic differences across the existing lineages. For example, the Australian lungfish still retains its limb-like fins, which once allowed its ancestors to navigate on land. Meanwhile, the fins of the African and South American lungfish evolved back into filamentous structures over the last 100 million years. “Our research also utilized experiments with CRISPR-Cas transgenic mice to demonstrate that this simplification of the fins is a result of changes in the Shh-signaling pathway,” Meyer explains.
This pathway is crucial during the embryonic development of various species, including determining the number and formation of fingers in mice, thereby offering further evidence of the evolutionary connection between the ray fins of bony fish and the fingers of terrestrial vertebrates. With the complete genome sequences of all existing lungfish families now available due to the recent research, further comparative genomic studies are anticipated to yield more insights into the lobe-finned ancestors of land vertebrates, helping to unravel the mystery of how vertebrates transitioned onto land.
