Sequencing of the Atlantic Cod Genome Reveals Immune System Surprise

A multinational team of genomic researchers has succeeded in obtaining the complete sequence of the genome of the Atlantic cod, a fish whose immune system differs radically from that of other fish or mammals.

Headquarters of the research effort was at the University of Oslo (Norway) where a Roche (Basel, Switzerland) 454 Sequencing System performed the critical sequencing operations. 454 Sequencing uses a large-scale parallel pyro sequencing system capable of sequencing roughly 400-600 megabases of DNA per 10-hour run on the Roche Genome Sequencer FLX with GS FLX Titanium series reagents.

The 454 Sequencing System relies on fixing DNA fragments to small DNA-capture beads in a water-in-oil emulsion. The DNA fixed to these beads is then amplified by PCR. Each DNA-bound bead is placed into a well on a PicoTiterPlate, a fiber optic chip. A mix of enzymes such as DNA polymerase, ATP sulfurylase, and luciferase are also packed into the well. The PicoTiterPlate is then placed into the GS FLX System for sequencing.

Results published in the August 10, 2011, online edition of the journal Nature revealed that the genome comprised 22,154 genes. Of particular interest was the finding that Atlantic cod had lost the genes for MHC II, CD4, and invariant chain (Ii) that are essential for the function of the immune system’s major histocompatibility complex (MHC) II pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. In place of the missing MHC II genes, the investigators found a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. Apparently, the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II.

“The overall aim of this initiative was to obtain the entire genome sequence of the Atlantic cod utilizing cutting edge sequencing technology,” said senor author Dr. Kjetill S. Jakobsen, professor of biology at the University of Oslo. “We had not expected to find that the Atlantic cod had lost such a crucial component of its immune system.”

“MHC II is something that you cannot really lose without suffering from some severe illness", said Dr. Jakobsen. “Mice genetically engineered to lack MHC II have immune defects. The fact that we see cod lacking MHC class II and actually doing well without it opens our eyes towards understanding human immunity.”

“This is another example of how 454 Sequencing Systems have helped a group make the transition from sequence to assembly to biological understanding,” said James Knight, a research fellow at Roche’s 454 Life Sciences. “With our long, accurate reads and optimized assembly software, any size laboratory can effectively carry out this type of large-scale project.”

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