Genetic secrets of cod revealed

The cod genome has now been sequenced. And it is only fitting that the star subject was a genuine Norwegian cod

Norway is the first nation to sequence the genetic material of this fish species – one that represents considerable economic value for the country.

By March this year the Norwegians had figured out most of the basic framework, and have spent these final months on the finishing touches. Today, 30 October, they can confidently announce to the world that Norway is the first to successfully apply the latest genome technology to sequence such a complex genome, although parts of the work still remain and their scientific article is not yet ready.

Race against time

In 2003, most but not all of the human genome had been sequenced after a 13-year-long effort. Researchers around the world are now looking to be the first to sequence species of significance in their homelands. Danish researchers have sequenced the pig genome, for example, and the Chinese have sequenced the panda bear’s genetic material. Fish such as zebrafish and stickleback have been sequenced before, but the Norwegians’ accomplishment marks the first genomic sequencing of a production fish species.

Project enhances national prestige

It is altogether fitting that Norway is sequencing the cod. “The cod is practically a national symbol for us Norwegians,” asserts Professor Kjetill S. Jakobsen of the Centre for Ecological and Evolutionary Synthesis (CEES), based at the Department of Biology, University of Oslo.

The competence and resource network is part of the national technology platform GenoFisk, which is under the auspices of the Research Council’s programme on Functional Genomics in Norway (FUGE), under the Large-scale Programme Initiative.

Unique immune system

Along the way, researchers have encountered major challenges and not a few surprises, explains the professor.

“The biggest surprise so far is that cod seem to have a very unique immune system that is clearly distinct from other sequenced species. We can’t say anything more about this until our scientific publication,” he adds cagily. “We have also found a malaria-like parasite in cod blood, which is exciting because it could indicate that fish may be vulnerable to diseases transmitted from other marine carrier species.”

“We believe more surprises are in store, related to both the adaptability of cod to temperature and oxygen uptake, and to factors that influence growth and maturation. All this knowledge can be applied to aquaculture production and management of cod stocks.”

25,000 genes

So far the researchers have been able to document nearly 25,000 cod genes. But there is still uncertainty around the exact number. That will be a topic for further study.

The cod family is large and diverse. Coastal cod off southern Norway, for instance, are quite different from cod found in the Barents Sea or the Baltic Sea. So although one cod has been sequenced, it does not tell us about all cod.

“But at least we now have a reference fish, which will make it easier to sequence the other cod strains eventually. We have already begun on that.”

The researchers hope to put together a genetic biobank with the various cod genomes to form a clear picture of their variations and to compare the characteristics of one cod strain with others.

New technology

The greatest challenge has been dealing with the sheer volume of data generated by two machines – quite small ones, actually – with the catchy name 454 FLX, each with a price tag in the NOK millions. Billions of fragments of the cod DNA molecule are fed into this device. What comes out has been fairly incomprehensible, even to a biologist such as Professor Jakobsen.

“For a job like this, it’s not enough to understand just the biology or just how to process the data. One really has to understand both aspects; it is tremendously difficult to find personnel with this dual competence.” Professor Jakobsen is convinced the project would not have been possible without the self-taught bioinformatics personnel involved, who sought education as biologists due to an interest in nature, but have ended up applying their computer skills as their most important tools The professor also praises the indispensible savvy of the IT experts who set up the entire calculation infrastructure.

Rather than the well-established Sanger method, the Norwegians took a chance and chose a completely new technology known as “massively parallel pyrosequencing”, a name derived from the massive amounts of data it processes.

“No one before us had ever attempted to sequence a genome as large as cod’s. So we didn’t know how it would go, analyzing scores of billions of gene sequences at once. It turned out to be very demanding. The original software couldn’t handle all the data, so it had to be developed and improved as we went,” explains Professor Jakobsen.

Advancing the research front

Steinar Bergseth, a special adviser at the Research Council, is very pleased about the project.

“The international community has been expecting Norway, as a prominent marine nation, to contribute significantly in this field. Now we have proven that we can. We have advanced the research front and shown the world that Norwegian researchers and research institutions have a lot to offer.

“The Research Council made a productive strategic move when we consolidated a number of fragmented competence centres into the national technology platform GenoFisk. Much of the cod project knowledge generated by that move will also be useful in sequencing the salmon genome.”

A goldmine for Norway?

Cod will very likely emerge as an economically vital production fish for Norway – so it is advantageous to know this species’ biology inside and out.

An overview of the cod genome will also provide a basis for improving the management of wild cod stocks. We know there are many stocks and strains of cod in the sea, but not how many and how different they are. With knowledge about the genome, we can identify the stocks and assess how much of each can be sustainably harvested.

Translation research needed

“But we basic researchers alone cannot convert this basic research into practical, applied knowledge,” emphasizes Professor Jakobsen. “That is a demanding task in itself, which requires funding as well as hard work and collaboration between research groups.”

“In the field of medicine they have what they call ‘translation research’ for converting basic research into clinical research. That is precisely what is needed in our field, too. We need translation researchers who can turn basic research into something to be applied to aquaculture.” Professor Jakobsen goes on to issue a challenge. “The Research Council should consider it one of their functions to put together a framework of research players that can take the knowledge we acquire and apply it usefully.”

Cod are similar to humans

During the sequencing process, the researchers were surprised at how many genes cod have in common with humans.

“The proportion of similar genes was totally unexpected. For a while we were joking that maybe the cod is the ancestor to humans,” winks the biologist. “But actually the overlap is due to the fact that the human genome at this point in time is more precise than that of any other species. So when we use humans as the reference, it’s natural to recognise lots of human genes in other species.”

Source: Research Council of Norway