Shark study yields key find in gene research

SINGAPORE- Singapore researchers have led the charge in decoding the elephant shark genome - the first from the shark family.

The work by 33 scientists in six countries shows how people and animals evolved from their sea-dwelling ancestors hundreds of millions of years ago, and has opened new avenues for bone disease and immunology research, scientists said.

The elephant shark is one of the cartilaginous fishes. This is the oldest living group of jawed vertebrates or animals with backbones that diverged from bony vertebrates - our predecessors - about 450 million years ago.

It was chosen because of its small genome - roughly one-third the size of humans'.

The deep-sea fish has been the slowest-evolving and least changed genome of all vertebrates, the scientists found.

"The slow-evolving genome of the elephant shark is probably the best proxy for the ancestor of all jawed vertebrates that became extinct a long time ago," said genome scientist Byrappa Venka-tesh, who heads the effort.

"So this work is a cornerstone for improving our understanding of the development and physiology of human and other vertebrates as we can see what has been added and what has been lost in 450 million years."

He also leads part of an international team that aims to decode the genetic make-up of thousands of animals called the Genome 10K project - the most ambitious endeavour since the Human Genome Project mapped the DNA of humans in 2001.

The work will let researchers see evolution in action by comparing animal and human genomes to reconstruct their evolutionary history, and predict how animals will respond to challenges such as climate change and pollution.

For instance, the latest effort comparing the elephant shark genome with the chemical blueprints of human and other vertebrates has revealed why the skeleton of sharks consists largely of cartilage instead of bones, said Prof Venkatesh, research director at the Institute of Molecular and Cell Biology, A*Star (Agency for Science, Technology and Research).

A family of genes found in all bony vertebrates was absent in the elephant shark, and when one of the genes was removed from the zebrafish, their bone formation depleted.

Bones were a major part of animals' evolution, explained Prof Venkatesh, because aquatic animals would have needed a scaffold to bear their body weight, and a calcium reservoir, when they made the transition onto land. By knowing which genes are involved in making and repairing bones, researchers can produce better drugs and treatments for diseases such as osteoporosis.

Said IMCB executive director Hong Wanjin: "This is a real breakthrough, which helped identify the genes important in bone formation in humans, so we can find ways to enhance or even inhibit bone formation to treat various diseases."

One unexpected finding, Prof Venkatesh noted, was that the elephant shark appears to lack special immune cells previously considered crucial for defending against viral and bacterial infections, and preventing autoimmune diseases such as diabetes and rheumatoid arthritis.

Despite their seemingly primitive immune system and their lack of special T-cells which help humans fight infection, sharks are healthy and have long lives - and this could point the way towards new treatments to improve immunity in people.

The work made the cover of the prestigious journal Nature this week.

Commenting on the work, Professor Rudolf Meier of the National University of Singapore's Biological Sciences department and Acting Director of Raffles Museum of Biodiversity Research said: "It's, of course, important to have all the branches in the trees of life represented in genomics, to be able, for instance, to reconstruct gene evolution and see where genes changed and novel traits emerged.

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