Martin Malmstrøm på fisketur

Martin Malmstrøm is fishing for genes. Photo: Michael Matschiner

Cod’s immune system is not special any more

For long we believed that the cod was a freak, who was fresh despite lack of immunity. But new research shows that all codfishes lack this immune component showing that the immune system generally is more flexible than previously thought.

In 2011 Kjetill S. Jakobsen led the project that for the first time sequenced the cod genome.

One surprising outcome was the finding that cod lacks an important part of the immune system, the so called MHCII, normally used for protecting against bacterial infections.

If humans were lacking MHCII we would have a significantly weakened immune system – a simple scratch or cold could mean death. Since 2011 researchers have wondered why cod, however, is going strong and not succumbing to illness.

– For a long time we thought that cod was an outlier – an evolutionary freak, says UiO Professor Kjetill S. Jakobsen. But, he continues:

– Now we have discovered that not only cod, but all species in the same group – the codfishes – lacks this part of the immune system. We also see several other changes in the fish immune system. Perhaps we are the real evolutionary freaks?

New approach to medical research

– These results demonstrate that the immune system is more flexible than previously realised, says UiO researcher Sissel Jentoft. She continues:

– This influences how we look at the immune system – also in humans.

These results could influence how we view the immune system in several species. Perhaps this will make scientists take a new approach to research on the immune system, i.e. when selecting which species to use as animal models.

The results is published in Nature Genetics.

For instance, cod could actually be a good model organism for research on organ transplants, precisely because it lacks the MHCII – but further research is necessary.

Farming cod is known to be very challenging. One reason is that they are prone to illness. With a different immune system, traditional vaccines have limited success. The new knowledge may be paving the way for better vaccines.

The stickleback smells its way to a partner

What is MHC?

MHC stands for major histocompatibility complex. This is a type of surface molecule essential to the immune system.

MCHII is the part of the immune system that detects foreign substances circulating in the blood stream. It is often called the “bacterial defense”.

MHCI is the part of the immune system that reports on what’s inside of the cells, i.e. in the case of a virus infection.

It has long been known that there is a connection between speciation and the immune system, but what causes this has not been entirely understood.

– We know for instance that stickleback chooses its mate based on smell. The smell of an individual is related to the immune system; two individuals with different immune systems smell differently.

– The stickleback smells its way to a mate with a compatible immune system, giving the offspring the best possible gene combination from both parents, Jakobsen explains.

Postdoctoral fellow Martin Malmstrøm is one of the leading authors of the publication, and elaborates:

– The part of the immune system related to smell is called MHCI. In this study we demonstrate that there is a correlation between the copy number of MHCI genes in a species and the number of species in the family. It looks like the choice of mate is dependent on MHCI.

– To a certain degree it is effective to choose a mate with a different immune system, but in most species there seems to be a limit in how different they can be. In cod-fishes the lack of MHCII apparently is compensated for by a substantial increase in the number of MHCI genes, leading to an even larger pressure towards choosing a mate that is similar. This may lead to genetic incompatibilities and thus in a longer term perspective promote speciation.

– Thus it seems like the loss of MHCII has resulted in the origination of more species in this group, compared to other fish groups.

Sissel Jentoft fisker etter gener

To further investigate if the lack of MHCII actually led to an increased number of species, the scientists had to fully sequence a large number of species.

The impressive number of 65 new species was sequenced to provide sufficient data.

In addition they carried out a new sequencing of the cod genome. This whole genome sequencing effort of 66 species actually more than doubled the number of whole genome sequenced fish species world-wide.

The “Big data” made available through this project will be invaluable for many projects to come.

When the 65 new species were sequenced, the researchers realised there was untidiness in the fishes’ family tree. Postdoctoral fellow Michael Matschiner was assigned the task of setting the record straight, and the publication could include a reorganised family tree.

100 million years with a “bad immune system”

The researchers even did some genetic archaeology. They looked into when the MHCII disappeared.

– It happened at a time when the earth went through substantial changes. Massive plate tectonic movement and climatic change resulted in new areas becoming available for the fishes, Jakobsen explains.

Matschiner elaborates:

– The cod-fishes represent an old branch that was primarily deep sea species. Probably there was less need for their existing immune system in the deep. Keeping a trait like the immune system is energy demanding, and perhaps the cod used less energy when this part of the immune system was eliminated.

Since then the cod-fishes differentiated and are now to be found not only in all oceans, but also in brackish water and freshwater. If speciation is used as a criterion for evolutionary success, we could say that the cod-fishes did well by losing the MHCII.

First published in Norwegian 12 September 2016

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Other stories in English


Professor Kjetill Jakobsen at Center for Ecological and Evolutionary Syntesis

Project Coordinator Sissel Jentoft Center for Ecological and Evolutionary Syntesis

Postdoctoral Fellow Martin Malstrøm Center for Ecological and Evolutionary Syntesis

Postdoctoral Fellow Michael Matschiner Center for Ecological and Evolutionary Syntesis