Another month, another paper, and like with last month’s, I picked another genetics paper, this time covering an interesting quirk of immunology.
This month’s paper from Nature talks about a species of fish that has made it to the dinner plates of many: the Atlantic Cod (Gadus morhua). The researchers applied shotgun sequencing techniques to look at the DNA of the Atlantic Cod. What they found about the Atlantic Cod’s immune system was very puzzling: animals with vertebra (so that includes fish, birds, reptiles, mammals, including humans!) tend to rely on proteins called Major Histocompatibility Complex (MHC) to trigger our adaptive immune systems. There tend to be two kinds of MHC proteins, conveniently called MHC I and MHC II:
- MHC I is found on almost every cell in the body – they act like a snapshot X-ray of sorts for your cells, revealing what’s going on inside. If a cell has been infected by an intracellular pathogen like a virus, the MHC I complexes on the cell will reveal abnormal proteins (an abnormal snapshot X-ray), triggering an immune response to destroy the cell.
- MHC II is found only on special cells called antigen-presenting cells. These cells are like advance scouts for your immune system – they roam your body searching for signs of infection. When they find it, they reveal these telltale abnormal proteins to the immune system, triggering an immune response to clear the infection.
The genome of the Atlantic cod, however, seemed to be completely lacking in genes for MHC II! In fact, when the researchers used computational methods to see how the Atlantic cod’s genome aligned with another fish species, the Stickleback (Gasterosteus aculeatus), it looked as if someone had simply cut the MHCII genes (highlighted in yellow) out! (see Supplemental Figure 17 below)
Yet, despite not having MHC II, Atlantic cod do not appear to suffer any serious susceptibility to disease. How could this be if they’re lacking one entire arm of their disease detection?One possible answer: they seemed to have compensated for their lack of MHC II by beefing up on MHC I! By looking at the RNA (the “working copy” of the DNA that is edited and used to create proteins) from Atlantic cod, the researchers were able to see a diverse range of MHC I complexes, which you can see in how wide the “family tree” of MHCs in Atlantic cod is relative to other species (see figure 3B, below).
Of course, that’s just a working theory – the researchers also found evidence of other adaptations on the part of Atlantic cod. The key question the authors don’t answer, presumably because they are fish genetics guys rather than fish immunologists, is how these adaptations work? Is it really an increase in MHC I diversity that helps the Atlantic cod compensate for the lack of MHC II? That sort of functional analysis rather than a purely genetic one would be very interesting to see.
The paper is definitely a testament to the interesting sorts of questions and investigations that genetic analysis can reveal and give a nice tantalizing clue to how alternative immune systems might work.
(Image credit – Atlantic Cod) (All figures from paper)
Paper: Star et al, “The Genome Sequence of Atlantic Cod Reveals a Unique Immune System.” Nature (Aug 2011). doi:10.1038/nature10342