Breathing new life into 'living fossil'

Genome-hunter Byrappa Venkatesh may not look the part, dressed neatly in a striped polo tee and sitting behind his desk at the Institute of Molecular and Cell Biology in Buona Vista.

But he has the heart of Victorian explorers of old - it is the gleam in his eyes that gives him away as he begins to talk.

He offers up tales of international fish expeditions - of freezing rivers in Hokkaido, Japan, where he has waded waist-deep to find lampreys - eel-like fish that resemble devilish monsters. He has also tracked elephant sharks in rough Australian waters and searched for eels in Europe.

Getting hold of blood samples from exotic fish has all been part of his quest to sequence their genomes for science, and to delve into the secrets their genes hold.

But of all the locations he has visited, it is a quiet hotel lobby in Changi Village here that sticks out most in his memory, he revealed.

It was there in 2000 that he finally got his hands on the most precious DNA of all: a sample of tissue from the coelacanth - a rare, ancient fish long thought extinct till it was found in 1938 off the South African coast.

Like lungfish - the other surviving lineage of lobe-finned fish - coelacanths are actually more closely related to humans and other mammals than to ray-finned fishes such as tuna and trout.

Ancient lobe fins were the first vertebrates to move from water onto land 395 million years ago, and the coelacanth genome is expected to reveal much about the origins of tetrapods, the evolutionary line that gave rise to amphibians, reptiles, birds and mammals.

Scientists believe that understanding more about the coelacanth promises insights not just into the ancient fish but into human biology itself.

Studying how coelacanth genes work and comparing them with ours could also, in the long run, offer clues to how to detect and treat human diseases better.

Professor Venkatesh's hunt for the elusive coelacanth - only 700 or so remain in the wild - began in 1997 when he read of then University of Berkeley researcher Mark Erdmann's stunning discovery of a specimen in a North Sulawesi fish market in Indonesia.

Previously, all the fish had been found in deep waters of the western Indian Ocean, near the Comoros.

"It became big news and I wrote to him... but he lost track of that fish and had to spend one more year in Manado to find another specimen."

Three years later, Dr Erdmann found himself passing through Singapore, and arranged to meet Professor Venkatesh at the Changi Village hotel he was staying at to pass him some frozen tissue samples.

They ended up missing each other - but the precious cargo still made it into Professor Venkatesh's hands.

"He had to catch an earlier flight out and handed over the test tube to a receptionist at the hotel. Till this day, we've never actually met. It was not a lot (of tissue), but we could do a lot of work with that," he said, chuckling.

Thirteen years on, Professor Venkatesh, working with 90 other international researchers, has become the first to sequence the genome of this legendary fish, dubbed a "living fossil" as it still exists in much the same form as it did 400 million years ago.

The team's genome work, which made it to the cover of leading scientific journal Nature in April, threw up a surprising finding.

It turns out that the coelacanth is not the fish species evolutionarily closest to the earliest land animals, despite what many had earlier thought. The honour may instead belong to the lungfish, a freshwater fish found in Africa and Australia.

Still, the coelacanth is related closely enough to tetrapods that it may hold many clues to exactly how ancient fish evolved into terrestrial creatures, said Professor Venkatesh.

"It is still very informative. It seems to have retained many features of land animals, including its physiology and metabolism."

Its bone structure, for instance, is somewhere between a fish fin and the limb of a land animal. And it excretes waste partially as ammonia - like fish do - and partly as urea, as land animals do.

The coelacanth and lungfish are both called lobe-finned fish because of their fleshy fins. But while the former has a genome about the same size as that of human beings - about three billion DNA base pairs - the lungfish's is some 40 times longer. Scientists do not fully understand why - but this makes it impossible to sequence the lungfish DNA at present.

The challenge now is to study the coelacanth genome to understand its physiology better, said Professor Venkatesh, a leader in the field of comparative genomics, where scientists compare human genes with those of the species' evolutionary ancestors, examining how they differ and what they share in common.

One exciting prospect would be to study the coelacanth's immune system, to shed light on how the human immune system evolved.

"If you understand our own biology better, then you can understand better how susceptible we are to certain diseases, and how we can improve our immunity to them," said Professor Venkatesh.

"New vaccines, drugs, they may come later. But first we need to understand our biology completely."

As his coelacanth research continues, Professor Venkatesh, who leaves the lab every two to three months to go on expeditions, is itching for his next adventure - finding and sequencing the genome of the ancient and critically endangered Chinese sturgeon.

"The genomes of these rare creatures are not only interesting in their own way, but also hold the key for understanding the origin, evolution and function of our own genome," he said.

davidee@sph.com.sg

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