Genome Of The Coelacanth Sequenced
April 18, 2013

Coelacanth Genome: Unexpected Insights From Fish With A 300-million-year-old Fossil Record

April Flowers for - Your Universe Online

The genome of the coelacanth, a creature with an evolutionary history that is both enigmatic and illuminating, has been decoded by the Genome Center of the Broad Institute of MIT and Harvard, and analyzed by an international team of researchers. The findings of this study are published in the journal Nature.

The coelacanth, a sea-cave dwelling, five-foot long fish with limb-like fins, was once thought to be extinct until a living specimen was discovered off the African coast in 1938. According to the AFP news agency, only 308 other coelacanths have been reported since.

Questions about this ancient-looking fish commonly referred to as "living fossils" have since loomed large in scientific circles. Modern coelacanths closely resemble the fossilized skeletons of their ancestors of more than 300 million years ago and the genome confirms what has long been suspected: coelacanth genes are evolving more slowly than other organisms.

"We found that the genes overall are evolving significantly slower than in every other fish and land vertebrate that we looked at," Jessica Alföldi, a research scientist at the Broad Institute, said in a statement. "This is the first time that we've had a big enough gene set to really see that."

The slow rate of evolutionary change might be because the coelacanths have not needed to change. For the most part, they live off the Eastern African coast (a second coelacanth species lives off the coast of Indonesia), at ocean depths where relatively little has changed over the millennia.

"We often talk about how species have changed over time," said Kerstin Lindblad-Toh, scientific director of the Broad Institute's vertebrate genome biology group. "But there are still a few places on Earth where organisms don't have to change, and this is one of them. Coelacanths are likely very specialized to such a specific, non-changing, extreme environment — it is ideally suited to the deep sea just the way it is."

Despite their resemblance to ancient ancestors, modern coelacanths are not a relic of the past brought back to life. They are a species that has survived and reproduced without large changes in appearance for millions of years. "It's not a living fossil; it's a living organism," said Alföldi. "It doesn't live in a time bubble; it lives in our world, which is why it's so fascinating to find out that its genes are evolving more slowly than ours."

The team has tested other long-debated questions as they decoded the coelacanth genome. Coelacanths have features that seem oddly similar to those seen only in land dwelling animals, for example. These features include "lobed" fins, which resemble the limbs of four-legged land animals known as tetrapods. Lungfish, another odd looking group of fish, also has lobed fins. Scientists have long thought that one of the ancestral lobed-finned fish species gave rise to the first amphibians, but until now they could not determine which of the two was a more likely candidate.

The team not only sequenced the entire genome of nearly 3 billion "letters" of DNA, they also examined the RNA content from both species of the coelacanth and the lungfish, allowing them to compare genes used in the brain, kidneys, liver, spleen and gut of the lungfish with gene sets from coelacanth and 20 other vertebrate species. The results of this examination suggest that tetrapods are more closely related to lungfish than coelacanths.

In order to understand what is often called the water-to-land transition, however, the coelacanth is still a critical organism to study. Although lungfish may be more closely related to land animals, its genome remains unreadable. The lungfish genome — at 100 billion "letters" - is simply too long and unwieldy for sequencing, assembly or analysis. The more modest-sized genome of the coelacanth, which is close in size to our own, yields valuable clues about the genetic changes that may have allowed tetrapods to flourish on land.

The team made several unusual discoveries when looking at what genes were lost when vertebrates came on land, as well as what regulatory elements — parts of the genome that govern where, when, and to what degree genes are active — were gained. Among these changes are sense of smell, immunity, evolutionary development and the urea cycle.

- Many regulatory changes have influenced the genes involved in smell perception and the detection of airborne odors. The team suggests that as animals moved from sea to land, a need arose for new means of detecting chemicals in the environment.

- A significant number of immune-related regulatory changes were found when the coelacanth genome was compared to those of land animals. These changes may be part of a response to new land-borne pathogens.

- The team found several key genetic regions that might have been "evolutionarily recruited" to form tetrapod innovations, including limbs, fingers and toes, and the mammalian placenta. One such region, HoxD, harbors a particular sequence that is shared across coelacanths and tetrapods, making it likely that this sequence was co-opted from the coelacanths to help form tetrapod hands and feet.

- Ammonia is excreted into the water by fish to get rid of nitrogen in their systems. Humans and other land animals, however, quickly convert ammonia into less toxic urea using the urea cycle. The team found that the most important gene involved in this cycle had been modified in tetrapods.

For researchers studying the evolution of tetrapods, the coelacanth genome may hold further clues. "This is just the beginning of many analyses on what the coelacanth can teach us about the emergence of land vertebrates, including humans, and, combined with modern empirical approaches, can lend insights into the mechanisms that have contributed to major evolutionary innovations," said Chris Amemiya, PhD., Director of Molecular Genetics at the Benaroya Research Institute at Virginia Mason (BRI). Amemiya is also Professor of Biology at the University of Washington.

For many reasons, sequencing the full coelacanth genome was a uniquely challenging exercise. Samples for research are nearly non-existent because the coelacanth is an endangered species, meaning that each sample obtained was precious. The researchers would have "one shot" at sequencing collected genetic material, according to Alföldi. This difficulty also seemed to knit the scientific community together. The LA Times reports that obtaining enough samples for genetic sequencing took decades; partially because they are "crazily endangered" and partially because sequencing technology wasn´t up to speed to decode the entire genome from the tiny samples the team had.

"The international nature of the work, its evolutionary value and history, and the fact that it was a technically challenging project really brought people together," said Lindblad-Toh. "We had representatives from every populated continent on earth working on this project."

Further study of the coelacanth's immunity, respiration, physiology, and more is needed to provide insights into how some vertebrates adapted to life on land, while others remained creatures of the sea. The research team is preparing several companion papers for publication in a special open access issue of the Journal of Experimental Zoology.

John Hutchinson, professor of evolutionary biomechanics from the Royal Veterinary College, told BBC News it was an interesting study.

"The lungfish-coelacanth question has gone back and forth over the years; the lungfish answer is not new, but this is a much better, bigger dataset so it does tip the balance a bit," he said. "They are missing some critical animals - it would be interesting to see what addition of salamander or more ray-finned fish would do to their analysis, but it might not change anything important."

There are other studies concerning the coelacanth, including one from the French organization Andromede Oceanology which is working with the Natural History Museum in Paris to attach acoustic tracking devices to the fish in order to study their behavior and capture 3D moving images of their fins as they swim.