By George Wigmore of Nature magazine

The sequencing of the Atlantic cod (Gadus morhua) genome has revealed an immune system never seen before in jawed vertebrates. The finding could be used to develop better vaccines and to improve disease management in farmed cod.

Kjetill Jakobsen, of the University of Oslo, and his colleagues found that Atlantic cod have lost the genes for three important components of the adaptive immune system, which fights pathogens and creates the immune memory that gives resistance to infection.

One missing component is called the major histocompatibility complex (MHC) II, which presents fragments of bacteria and other pathogens to cells in the immune system to trigger a wider response. Cod also lack the gene for the proteins CD4, which interacts with MHC II, and invariant chain, which is involved in making and transporting MHC II.

"MHC II is something that you can't really lose without suffering from some severe illness", says Jakobsen. Mice genetically engineered to lack MHC II have immune defects.

The finding "is quite unexpected" says Sebastian Fugmann, a molecular immunologist at the National Institute on Aging in Baltimore, Maryland. "This is the most dramatic example reported thus far of the plasticity of the adaptive immune system in jawed vertebrates on an evolutionary timescale."

Genetic make-up

One way that cod compensate for their missing MHC II is by having ten times more genes than other vertebrates, including related fish species and humans, for another component of the immune system, called MHC I. MHC I takes proteins from within the cell, and displays them on the cell surface. If the immune system detects any foreign bodies, such as viral proteins, it destroys the infected cell.

Jakobsen and his team found that cod also rely more heavily than other vertebrates on molecules called Toll-like receptors. These molecules, which recognize bacterial and viral invaders, are part of the more evolutionarily ancient innate immune system.

The Atlantic cod has long been seen as a potentially important aquaculture species, but infections, such as from the bacterium Francisella noatunensis, are a major barrier to cod farming. The findings could allow targeted vaccine development, aiding disease management and the domestication of Atlantic cod.

But it may not be that simple, says Jakobsen. "Most vaccines are directed towards the function of MHC II. So this may imply that we have to think differently when making vaccines for cod compared with, for example, salmon," he says.

The finding could also challenge our understanding of the evolution and flexibility of the vertebrate immune system.

"The fact that we see cod lacking MHC class II and actually doing well without it opens our eyes towards understanding human immunity", says Jakobsen. All the other genes in the MHC II pathway are present, he says, suggesting that cod may have found other uses for these genes.

Not everyone is surprised by the finding. "It's old news with a proof at molecular level," says Ioanna Katsiadaki, a fish endocrinologist at the Centre for Environment, Fisheries & Aquaculture Science in Weymouth, UK. "We knew that cod respond poorly in terms of antibodies many years back and the impaired MHC class II system has been suggested as the reason. So the paper provides only a confirmation of what has been known for years." The sequencing of related species may reveal similar adaptations. "It would be really interesting to look at the comparative genomics of those species closest to cod," says Jakobsen. He speculates that cod may owe their unusual immune system to having evolved in deep waters with a very specific set of pathogens. A similar system, with expanded MHC I and reduced MHC II, has evolved independently in the amphibian axolotl (Ambystoma mexicanum).

This article is reproduced with permission from the magazine Nature. The article was first published on August 10, 2011.