Jawless Lamprey Takes a Bite out of Oncogene Evolution

Mice, fruit flies and dogs are common creatures of laboratories across the country, valuable to researchers for their genetic proximity to humans. But what about lampreys?

A new Yale School of Public Health study has enlisted this unlikely and slimy ally in the fight against cancer.

By carefully tracing the evolution of a select number of cancer-causing genes in a variety of species, the researchers evaluated which animals are — and are not — effective in gauging how an analogue of those genes in humans can lead to cancer. What they found is surprising: jawless fish such as lampreys share significant similarities in these certain genes compared to humans, while fruit flies do not. Their findings, published in the journal Genome Biology and Evolution, will help molecular biologists and other scientists as they work to find potential cures to certain cancers, such as lymphoma.

The specific genes the researchers investigated are known to play a large role in a variety of cancers, including neuroblastoma, non-small-cell lung cancer and anaplastic large-cell lymphoma. And by knowing how these genes work together in other species, they can make educated guesses about how they work and can cause cancer in humans.

But there are limitations: The genes don't necessarily work together in the same way, said YSPH Jeffrey Townsend, Ph.D., the senior author of the paper and the Elihu Professor of Biostatistics in the Department of Biostatistics.

That’s where lampreys come in. To fully understand how the genes relate in diverse model organisms requires analysis of the gene sequence in many organisms. After all, these species diverged from humans’ ancestors many millions of years ago — quite a long time for genes to mutate, recombine, drift and even disappear entirely.

“That makes it really hard to figure out how all the genes are relating to each other,” he said. “It becomes quite a puzzle—one which evolutionary biologists like to solve, and one that illuminates a path toward new cancer therapies.”

“If you do an experiment in an organism for which that relationship between the [cancer genes] is not the same relationship as it is in humans, you’re going to get answers that have nothing to do with how to treat cancer in humans,” Townsend said.

“What we did was we sorted all that out to tell you which organisms you can go and do studies on, to figure out things about these cancer genes, so that we can generate drugs to treat cancer in humans.”

Their results are a promising step toward a deeper understanding of cancer’s causes, and of what it takes to make drugs that can stop it.

At first glance, it may be difficult to see just how helpful these jawless eels are to researchers. Other conventional lab animals have evolved enough differences in their anaplastic lymphoma kinase, leukocyte tyrosine kinase and other genes that it’s difficult to figure out similarities. Lampreys, on the other hand, hold the key: they are the most distant relative of humans in which the interactions between these genes are the same as in humans; the presence of these genes operating in the same way as it does in humans helps researchers to decode their relationships in other model organisms.

Townsend’s interdisciplinary team also consisted of researchers from the University of North Carolina at Charlotte, the Chinese Academy of Agricultural Sciences and the Yale Center for Genome Analysis.