UW News

July 23, 2009

Ancient sea lamprey dramatically transforms its genome

UW Health Sciences/UW Medicine

Researchers have discovered that the sea lamprey, which emerged from jawless fish first appearing 500 million years ago, dramatically remodels its genome. Shortly after a fertilized lamprey egg divides into several cells, the growing embryo discards millions of units of its DNA.


The findings were published this month in the Proceedings of the National Academy of Sciences. The lead author is Jeramiah Smith, a UW postdoctoral fellow in genome sciences working in the Benaroya Research Institute laboratory of Chris Amemiya, who is also a UW affiliate professor of biology.


Theirs is believed to be the first recorded observation of a vertebrate — an animal with a spinal column — extensively reorganizing its genome as a normal part of development. A few invertebrate species, like some roundworms, have been shown to undergo extensive genome remodeling. However, stability was thought to be vital in vertebrates’ genomes to assure their highly precise, normal functioning. Only slight modifications to allow for immune response were believed to occur in the vertebrate genome, not broad-scale rearrangements.


Smith, Amemiya and their research team inadvertently discovered the dynamic transformations in the sea lamprey genome while studying the genetic origins of its immune system. The researchers were trying to deduce how the sea lamprey employs a copy-and-paste mechanism to generate diverse receptors for detecting a variety of pathogens.


The researchers were surprised to notice a difference between the genome structure in the germline — the cells that become eggs and the sperm that fertilize them — and the genome structure in the resulting embryonic cells. The DNA in the early embryonic cells had myriad breaks that resembled those in dying cells …but the cells weren’t dying. The embryonic cells had considerably fewer repeat DNA sequences than did the sperm cells and their precursors.


The alteration of the sea lamprey genome and of invertebrates that restructure their genome appears to be tightly regulated, according to Smith, yet the resulting structural changes seem almost like the DNA errors that give rise to cancers or other genomic disorders in higher animals. Learning how sea lamprey DNA rearrangements are regulated during development might provide information on what stabilizes or changes the genome, he said, as well the role of restructuring in helping form different types of body cells, like fin cells, muscle cells, or liver cells.


Researchers do not yet know how the sea lamprey’s genome guides the morphing it undergoes during its life. Sea lampreys have a long juvenile life as larvae in fresh water, where they eat on their own. Their short adult lives are normally spent in the sea as blood-sucking parasites. Their round, jawless mouths stick like suction cups to other fish. Several circular rows of teeth rasp through the skin of their unlucky hosts. Their appetite is voracious.


Later, as they return to streams and rivers along the northern Atlantic seaboard, sea lampreys atrophy until they are little more than vehicles for reproduction. After mating, they perish. Populations of sea lamprey were landlocked in the Great Lakes and other nearby large lakes after canals and dams were built in the early 1900’s. They thrive by parasitizing (and killing) commercially important fish species and are considered a nuisance in the Great Lakes region.


Biologists are interested in the sea lamprey partly because of its alternating lifestyles, but largely because it represents a living fossil from around the time vertebrates originated. Lampreys were on earth before the dinosaurs. It’s possible that their dynamic genome biology might someday be traced back in evolutionary history to a point near, and perhaps including, a common ancestor of all vertebrates living today, the authors of the study noted.


“Sea lampreys have a half billion years of evolutionary history,” Smith said. “Evolutionary biologists and geneticists can compare their genomes to other vertebrates and humans to see what parts of the lamprey genome might have been present in our primitive ancestors. We might begin to understand how changes in the sea lamprey genome led to their distinct body structure and how fishes evolved from jawless to jawed.”


In addition to Smith and Amemiya, the other researchers on this study were Francesca Antonacci and Evan E. Eichler of the UW Department of Genome Sciences. Research grants from the National Institutes of Health, the National Science Foundation and the Howard Hughes Medical Institute funded the project. Smith also received National Research Service Awards, including an Institutional Ruth L. Krischstein Award through the UW Department of Genome Sciences and an individual Ruth L. Krischstein Award through the National Institute of General Medical Sciences.