Sunfish study may benefit humans

The ocean sunfish can grow up to a length of 2.7m and weigh up to 2.3 tonnes. Its size could increase its survival rate and help it produce more eggs than any other animal, says Professor Byrappa Venkatesh.
The ocean sunfish can grow up to a length of 2.7m and weigh up to 2.3 tonnes. Its size could increase its survival rate and help it produce more eggs than any other animal, says Professor Byrappa Venkatesh.PHOTO: ISTOCKPHOTO
The ocean sunfish can grow up to a length of 2.7m and weigh up to 2.3 tonnes. Its size could increase its survival rate and help it produce more eggs than any other animal, says Professor Byrappa Venkatesh.
Professor Byrappa Venkatesh

Both share similar genes, a finding that could help growth-related disease treatment

Singapore divers flock to places such as Bali for a glimpse of a strange fish that can grow as big as a minibus.

But the study of the ocean sunfish, or Mola mola, may benefit humans in ways beyond recreational sightseeing.

The genetic blueprint of the giant fish - which can grow up to a length of 2.7m and weigh up to 2.3 tonnes - may pave the way for the development of treatments for growth-related diseases in humans.

Donohue syndrome, for example, is a human disorder characterised by severe insulin resistance and stunted growth. There is currently no cure for it.

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Scientists at the Agency for Science, Technology and Research (A*Star), working with international partners, have found that both humans and Mola mola have similar genes involved in their growth hormone signalling pathway. This pathway refers to a series of genetic processes that contribute to the growth of the organism.

Growth hormones in both the sunfish and humans are secreted by the pituitary gland, which is located at the base of the brain.

The hormone, made up of building blocks known as amino acids, is carried in the bloodstream to organs, including the liver. There, it binds with a growth hormone receptor present in liver cells.

The study lead, Professor Byrappa Venkatesh, research director at A*Star's Institute of Molecular and Cell Biology, found that the mutation in the gene that gives the Mola mola its size, is the same gene that in humans mutates to give rise to growth diseases.

This "binding" is similar to how pieces of a jigsaw puzzle fit together - a successful "bind" gives the cell permission to carry out instructions mapped out by a specific gene carried in DNA in the cell's nucleus.

Successful "binding" could cause, for example, the production of a hormone that promotes growth, called insulin-like growth factor.

The insulin-like growth factor in turn binds with other receptors, resulting in a cascading effect that causes cells to multiply and grow, eventually leading to growth of the organism.

However, problems arise when there are kinks in the pathway, caused by mutations in the amino-acid building blocks.

The study lead, Professor Byrappa Venkatesh, research director at A*Star's Institute of Molecular and Cell Biology, found that the mutation in the gene that gives the Mola mola its size is the same gene that in humans mutates to give rise to growth diseases.

"The same amino acid, if it mutates in one way, results in dysfunction. But if it changes in a different way, it increases its efficiency to bind to the receptor - a positive selection," Prof Venkatesh said.

The sunfish's large size could help with its survival rate, and help it produce more sperm and eggs, increasing its chances of survival, he added. The study was published in the science journal GigaScience.

The Mola mola produces more eggs than any other animal - up to 300 million eggs per individual every year. Further research in this area could pave the way for more in-depth research on the function of these genes in human health and diseases, particularly growth-related diseases, said Prof Venkatesh.

"From this, we can learn how to make a better growth hormone receptor - a chemical that can increase the binding," he said.

The three-year research was done by Prof Venkatesh's laboratory in collaboration with researchers from the China National Genebank, BGI-Shenzhen.

The scientists sequenced the genome of the Mola mola, and compared it with that of humans as well as other animals. The sequencing was part of the Genome 10K project, which aims to catalogue genomes of 10,000 vertebrate species.

This genomic zoo is an important resource for comparative genomics, which seeks to better understand the structure, function and evolution of the human genome by comparing it with genomes of other vertebrates (creatures with backbones).

Prof Venkatesh and collaborators in China and Germany have also sequenced the whole genome of the tiger tail seahorse, which is native to Singapore.

One of the findings was that the seahorse lacked a master control gene that is in charge of regulating the development of pelvic fins in fishes, or legs in humans.

The study concluded that the loss of this gene led to the loss of pelvic fins in seahorses, providing insight into the genes involved in the human disease. Mutations in this gene in humans have been associated with genetic diseases related to leg development, such as the small patella (kneecap) syndrome.

A version of this article appeared in the print edition of The Straits Times on May 26, 2017, with the headline 'Sunfish study may benefit humans'. Print Edition | Subscribe