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Rhodes’ academics part of a historic coelacanth genome international research and decoding team

Date Released: Wed, 17 April 2013 14:40 +0200

This week, Professor Rosemary Dorrington, Rhodes Visiting Professor Gregory Blatch and Dr Adrienne Edkins, along with colleagues, who were part of an international team of researchers, celebrate the successful decoding of the genome of a creature whose evolutionary history is both enigmatic and illuminating: the African coelacanth.

The work of the three Department of Biochemistry, Microbiology & Biotechnology staff members, who collaborated with international researchers from Massachusetts Institute of Technology (MIT) and Harvard University, among others, led to the co-authoring of an academic paper on the coelacanth genome which appears in the April 18th issue of Nature.

Prof Dorrington led the South African project to collect coelacanth tissue samples for the genome project, while Prof Blatch and Dr Edkins were involved in the analysis of stress proteins in the coelacanth.

Also involved from Rhodes were Prof Blatch’s PhD student, Mr William Modisakeng (now a patent attorney in Gauteng) and Mrs Val Hodgson who provided technical support. 

A sea-cave dwelling, 1.5 m long fish with limb-like fins nick-named “Old four-legs”, the coelacanth was once thought to be extinct. A living coelacanth was discovered off the Eastern Cape coast in 1938 by Margaret Courtney-Latimer and since then, questions about these ancient-looking fish – popularly known as “living fossils” – have loomed large.

Coelacanths today closely resemble the fossilized skeletons of their more than 300-million-year-old ancestors. The genome sequence confirms what many researchers had long suspected: genes in coelacanths are evolving more slowly than in other organisms.

“We found that the genes overall are evolving significantly slower than in every other fish and land vertebrats that we looked at,” said Dr Jessica Alföldi, a research scientist at the Broad Institute of MIT and Harvard Universities in the USA and co-first author of a paper on the coelacanth genome, which appears in the April 18th issue of Nature.

“This is the first time that we’ve had a big enough gene set to really see that,” she said.

Researchers hypothesize that this slow rate of change may be because coelacanths simply have not needed to change: they live primarily off of 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 and senior author.

“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.”

Because of their resemblance to fossils dating back millions of years, coelacanths today are often referred to as “living fossils” – a term coined by Charles Darwin. But the coelacanth is not a relic of the past brought back to life: it is a species that has survived, reproduced, but changed very little 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 coelacanth genes are evolving more slowly than ours.”

The coelacanth genome sequence has also allowed scientists to answer other long-debated questions. For example, coelacanths possess some features that look oddly similar to those seen only in animals that dwell on land, including “lobed” fins, which resemble the limbs of four-legged land animals (known as tetrapods).

Another odd-looking group of fish known as lungfish possesses lobed fins too. It is likely that one of the ancestral lobed-finned fish species gave rise to the first four-legged amphibious creatures to climb out of the water and up on to land. However, until now, researchers could not determine which of the two is the more likely candidate.

In addition to sequencing the full genome – nearly 3 billion “letters” or bases of DNA – from the coelacanth, the researchers also looked at RNA content from coelacanth (both the African and Indonesian species) and from the lungfish.

This information allowed them to compare genes in use in the brain, kidneys, liver, spleen and gut of lungfish with gene sets from coelacanth and 20 other vertebrate species. Their results suggested that tetrapods are more closely related to lungfish than to the coelacanth.

However, the coelacanth is still a critical organism to study in order to understand what is often called the water-to-land transition. Lungfish may be more closely related to land animals, but its genome remains inscrutable: at 100 billion bases in length, the lungfish genome is simply too unwieldy for scientists to sequence, assemble, and analyze.

The coelacanth’s more modest-sized genome (comparable in length to our own) is yielding valuable clues about the genetic changes that may have allowed tetrapods to flourish on land.

By 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 identified and the researchers made several unexpected and exciting discoveries as reported in Nature.

“Blatch and I initiated the South African coelacanth genome initiative after the discovery of coelacanths off Sodwana Bay by recreational divers in 2000. 

“We had no idea how ambitious the project would be - the coelacanth genome is equivalent in size to the human genome, the sequencing of which took 10 years to complete and involved more than 20 research institutes and hundreds of hundreds of researchers,” says Prof Dorrington. 

“Our naiveté was probably an asset because we decided that the magnitude of the project should not be the reason to at least get started!” she says. 

According to Prof Dorrington, the idea was supported by the then Department of Arts, Culture Science and Technology (DACST), “who put funding into what would become the African Coelacanth Ecosystem Programme that is still running today”.

“It is rare as a researcher to have the privilege of being able to be involved in a research project that is of general such interest to the broader science community,” she says.

“I am always struck by research on the coelacanth has always been able to inspire great excitement and interest amongst my colleagues, even if they are not directly working in the same field,” says Prof Dorrington.

“It was a great privilege to work with such a great team of people led by Chris Amemiya, and Jessica Alföldi who led the genome sequencing team,” she adds.

Rhodes researchers, including Dr Edkins and Dr Ozlem Tastan-Bishop, together with Prof Blatch, are currently involved in subsequent genome analyses that will be published shortly in a separate manuscript.