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March 7, 2016

Fresh discoveries from an old fish: Gar is the new biomedical friend of zebrafish and human

The genome of a slowly evolving fish, the spotted gar, is very similar to the genomes of both zebrafish and humans, and can be used as a "bridge species" that opens a pathway to important advancements in biomedical research focused on human diseases. That is the conclusion of an international research consortium outlined in a paper lead-authored by newly appointed MSU assistant professor Ingo Braasch.

“There are potentially thousands of connections that can be made now from human to zebrafish and back through gar as a steppingstone,” said Braasch, a postdoctoral researcher at the University of Oregon during the project and now an assistant professor in the Department of Integrative Biology at MSU. “This points to a better way to perform biomedical research for studying human disease in zebrafish. With higher precision, researchers will be able to find the right region in the genome of zebrafish to design experiments and mutation models.”

The team’s discovery means that biomedical researchers should be able to identify a disease-associated genetic region in humans, locate the corresponding region in the spotted gar and then investigate the appropriate location in the genomes of zebrafish or other fish models to potentially understand disease development. Zebrafish are often used as a model fish in biomedical research, but due to their genetic divergence from humans it can be difficult to make direct biological comparisons.

“The gar is evolving slowly, which means that it has kept more ancestral elements in its genome than other lineages, like for example zebrafish. Surprisingly, gar chromosomes are very similar to chromosomes of birds,” Braasch said. “Comparisons of human to gar are also less confusing because the gar does not have all the extra gene copies that the zebrafish has from a genome duplication that occurred in the lineage of modern fishes.”

In the wide-ranging research effort, led by the University of Oregon in collaboration with the Broad Institute at MIT and Harvard University, researchers sequenced the genome of the spotted gar (Lepisosteus oculatus) – an ancient fish with hard diamond-shaped scales and a long mouth filled with needle-like teeth. Gars today are found in U.S. states along the Gulf of Mexico, up the Mississippi River to Michigan in North America, as well as in Central America and Cuba.

The spotted gar genome, Braasch said, offers a window into the evolution of vertebrate body plans, including, for example, how fins evolved into limbs that allowed fish to walk onto land. In addition, gars have enamel-bearing teeth and strong scales containing ganoin, which has long been thought to be a type of enamel similar to that found on human teeth. The group’s gene expression studies now suggest that our teeth originated from genetic programs that formed protective scales in the skin of ancient armored fish and that are still found in gar.

Braasch will continue this research in his new position and lab at MSU, where he will build upon the results of the spotted gar genome project.

“We are using gar to further improve comparisons of human to zebrafish and thereby help to make zebrafish an even better model system for disease research,” Braasch said. “And by studying gar and zebrafish side-by-side here in my lab at MSU, we also hope to answer many more evolutionary questions about the origin of vertebrate genomes and their biology.”

The research is detailed in a paper currently published online in the journal Nature Genetics, co-authored by 61 researchers from 33 institutions.