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Life Sciences
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Fish Edits Its Own Genome By Cutting And Splicing DNA During Development

Removing 20 percent of all genetic material in the body may not sound like the greatest idea to most people, but for sea lampreys, this is standard procedure.

Sea lampreys are eel-like fish native to the coastal regions of both sides of the Atlantic Ocean. These organisms undergo a dramatic genome remodeling as a normal part of their growth cycle, according to work published in the Proceedings of the National Academy of Sciences. This marks the first observation of this phenomenon in a vertebrate: an organism with a backbone.

Biologists have long thought that vertebrate genomes required stability in order to function normally, but the sea lamprey demonstrates that stable vertebrate genomes are not necessary. Days after a sea lamprey egg is fertilized and begins to divide, the cells that eventually make up the organisms body begin to differentiate. Those that become the sex cells, or the germline, retain all of the genetic material inherited from the parents; but the cells that eventually become the rest of the sea lamprey body, or somatic cells, expunge large amounts of genetic material.

"We are most interested in rearrangements that happen within the lifespan of individuals," says the study's lead author Jeramiah Smith, a postdoctoral associate in genome sciences at the University of Washington who works in the lab of Chris Amemyia at the Benaroya Research Institute at Virginia Mason in Seattle. He adds that the team seeks "a better understanding of the evolutionary starting point of vertebrate genomes."

Sea lampreys are a great model organism for this work because they are the first group of vertebrates to have emerged some 500 million years ago. Understanding the processes that contribute to this loss of genetic material may ultimately provide a better understanding of the factors that underlie and influence the stability of vertebrate genomes.

It might be that the DNA is removed in order to silence these genes permanently, or "maybe this is an example of how chromosome rearrangement is necessary to get the right tissue development," suggests Gerald Smith of the Fred Hutchinson Cancer Research Center. Although he stresses that genome rearrangements are relatively common in all life forms, the largest of these results in the loss of, at most, a few hundred thousand units of DNA and very few unique genes in vertebrates. None is as drastic as the loss of hundreds of millions of units of DNA and many genes, as is the case in sea lampreys.

There are isolated examples of small-scale gene rearrangements that occur in every vertebrate organism. The best studied involves minor modifications during the development of the immune system, the body's defense system against infection, but these are observed in individual cells and not in entire tissues as is seen in sea lampreys. "It's really surprising, there was nothing known about these rearrangements in embryos," says Marianne Bronner-Fraser of the biology division of the California Institute of Technology. "We've always assumed that every cell in an animal was the same, but this is not the case for lamprey."

DNA loss in sea lampreys was discovered when the researchers began looking at the total DNA content of cells from different tissues in the sea lamprey (e.g. muscle, kidney, and sperm). It became apparent that sperm cells contained much more DNA than those from other tissues. The DNA loss that occurs in sea lamprey somatic cells also results in the loss of numerous genes. The most common loss was in a sequence that is repeated numerous times in the germline that has been named germ1. Smith and colleagues were able to track germ1 in both the germline and the somatic cells to directly monitor the loss of DNA during the early growth stages of sea lamprey embryos. However, the function of germ1 in the germline and why it is removed from somatic cells is still unclear.

Most people know of sea lampreys as nuisance organisms that get into areas like the Great Lakes and cause numerous ecological problems because they prey on the natural fish populations. According to Marc Gaden of the Great Lakes Fisheries Commission (GLFC), invasive lampreys can consume up to 40 pounds of fish each year. The GLFC spends millions of dollars annually to try and control the problem of sea lamprey predation in the Great Lakes. Gaden says, "Studying lamprey and its lifestyle and anything having to do with its genome could unlock a portion of its lifestyle to help with control."

Kyle Costa is a graduate student in the Department of Microbiology and in the Astrobiology Program at the University of Washington.


Top: Jeramiah Smith, University of Washington (UW) postdoctoral fellow in genome sciences, holds a sea lamprey in a fish husbandry laboratory in California. Photo: UW

Bottom: Sea lamprey's jawless mouth with concentric rows of teeth and toothed tongue. Photo: Great Lakes Fisheries Commission

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