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Norwegian-Led Group Sequences Atlantic Cod Genome, Finds Unique Immune System

NEW YORK (GenomeWeb News) – A Norwegian-led research team that sequenced and analyzed the Atlantic cod, Gadus morhua, reported online today in Nature that the fish has an immune system unlike any found in other jawed vertebrates so far.

By annotating and analyzing the genome, which they sequenced with the Roche 454 platform, the researchers found genetic clues to Atlantic cod biology, including variations in a hemoglobin gene that appear to help the fish survive temperature shifts. The team also found evidence that the fish relies on an immune system that lacks some genes in MHCII — a major histocompatibility complex component with a central role in adaptive immunity in most jawed vertebrates.

Instead, their genome analyses point to expansions and rearrangements in other immune pathways, senior author Kjetill Jakobsen, a biologist at the University of Oslo, and co-authors explained, noting that the fish "has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHCII."

"These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates," they added.

The team used Roche 454 GS FLX Titanium sequencing to generate about 40 times coverage of the 830 million base pair Atlantic cod genome from shotgun and paired-end libraries created with genomic DNA from a heterozygous male Atlantic cod fish.

"Our study shows quite clearly that this approach solely using 454 Systems gives excellent results for large genome sequencing and de novo assembly projects," Jakobsen said in a statement. "We found that the long reads were essential to obtaining the desired quality of results to achieve our research goals."

After assembling the genome with two methods, Newbler and Celera, the researchers filled in gaps and tracked down sequence variants by comparing Roche 454 and Illumina sequence reads to the Newbler assembly.

When they analyzed the genome, the team detected 22,154 predicted protein-coding sequences. Of these, more than 17,900 were identified by trying to map stickleback protein-coding sequences onto the cod genome.

Further comparisons indicate that the cod genome contains most of the main pathways found in related fish. But researchers found some important differences: the Atlantic cod appears to be missing genes that are considered critical for the function of the MHCII pathway, which typically contributes to helper T-cell activation by the adaptive immune system in jawed vertebrates. For instance, the genome contained a truncated pseudogene version of the gene that normally codes for CD4.

Even so, the researchers explained, the fish does not appear to be especially susceptible to infections by bacteria and parasites, which are usually targeted by the adaptive immune system. Their analyses suggest that there are compensatory changes in other immune pathways including expansions involving genes in MHC I and reconfigured versions of the Toll-like receptor pathways.

The researchers also found SNPs that appear to explain several aspects of Atlantic cod biology — including new and known hemoglobin gene polymorphisms that are thought to contribute to the Atlantic cod's ability to survive in frigid water and adapt to changing water temperatures.

They also tracked down genetic patterns that they say may eventually prove useful for helping to manage the commercially important fish species. For now, the team plans to use transcriptome sequence information and other data to continue refining the cod genome assembly and annotation to get more details about the fish's biology.

"This work provides a major foundation for addressing key issues related to the management of natural Atlantic cod populations, such as the concept of fisheries-induced evolution, which dictates that selective harvesting can change the evolutionary trajectory of major life-history traits of natural populations," the researchers wrote.

"Moreover," they added, "our novel findings regarding the immune system will allow for more targeted vaccine development, aiding disease management and the process of domestication of Atlantic cod."