The secret of a long life

There may be a cure for cancer lurking in the genes of an ancient fish.  At least, that’s the hope of University of Kentucky genetic biologist Jeremiah Smith.  With a $1.5 million-dollar, five-year grant from the National Institutes of Health, Smith is working to understand how the lamprey—a fish that is virtually unchanged in the last 450million years—can discard troublesome parts of its genome, and thus, seemingly escape cancers and other genetically-related disease.

Jeremiah Smith became a biologist because he fell in love with fossils.  On his parent’s South Dakota ranch, there were dinosaurs in the hills, fish in the prairie, and more life in the ancient rocks than anywhere else. While he liked everything biological, Smith, now a professor of biology at the University of Kentucky, understood that life has a long history, and that some species of fish, amphibians, and reptiles have remained unchanged for very long time.  That history, Smith noted, was expressed in each organism’s genetic code. And the longer in time that a species has persisted, the more its genome could tell us about its tricks for survival.

Pacific lamprey are among many species of lamprey that discard a portion of their genes as a way of avoiding disease.

Pacific lamprey are among many species of lamprey that discard a portion of their genes as a way of avoiding disease.

Two fish are the undisputed champions of species longevity: the coelacanth and the lamprey. Coelacanths– a lobe-finned fish ancestral to land animals–were thought to be extinct for at least 70 million years.  But in 1938, they were discovered in the ocean depths off East Africa.  Lamprey, an eel-like parasitic fish that lacks jaws, is even older. Lampreys have persisted for at least 450 million years virtually unchanged from their fossilized ancestors.

Smith began his career studying the coelacanth’s ancient genome. Coelacanths– a lobe-finned fish ancestral to land animals–were thought to be extinct for at least 70 million years.  But in 1938, they were discovered in the ocean depths off East Africa.  In 2013, Smith was part of the team that unraveled its genetic code. Surprisingly, results demonstrated that genes involved in immunity and nitrogen excretion were important in adapting to life on land, as well as the more anticipated development of  tail, ear, eye, brain and smell.

Jeremiah Smith and two graduate students are exploring the lamprey genome for clues to curing many human genetic diseases.

Jeremiah Smith and two graduate students are exploring the lamprey genome for clues to curing many human genetic diseases.

Then Smith turned his attention to an even more ancient fish—the lamprey. Smith is working to understand how the lamprey—a fish that is almost unchanged in the last 450 million years—can discard troublesome parts of its genome, and thus, seemingly escape cancers and other genetically-related disease. Decoded, this may contribute to prevention or cures for human cancers immune-system disorders, and other maladies..

Every cell in the human body contains the same DNA.  Lampreys harbor two different sets of DNA.  As embryos, they archive a complete set of genes in their reproductive cells, but then discard about 20% of the DNA from the cells that will become their body and tissues. These are genes that, if damaged or inaccurately reproduced as a cell grows or divides leave lamprey vulnerable to run-away cell division, or to inaccuracies in the cell’s genetic materials–resulting in probable cancer, aging, and other gene-related maladies. While these genes are essential to keep in the reproducive cells, having them in the rest of the body is a liability. “The fact that lamprey are getting rid of these genes suggest they know something we don’t.” Smith noted.

With a 1.5 million-dollar grant from the National Institute of Health, Smith will determine exactly what the discarded lamprey genes control, and, importantly, whether the human equivalent genes behave in the same way.  In the genes of an ancient fish, may lie secrets to curing and preventing much human disease.

And such a mechanism for preventing disease may explain why some species persist unchanged for so long. Another venerable animal, the hagfish, has been unchanged for at lease 500 million years, and may date to the original Cambrian explosion of life.  Like the lamprey, it discards a portion of its genes.  There is, says Smith, some evidence that perhaps the coelacanth does the same.  A valuable lesson, perhaps for leading an uncluttered life, right down to the very basics.

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