Biologists identify genes that cause melanoma in swordtail fish hybrids

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For nearly 100 years, scientists have known that hybridization, or intermixing, within species often results in offspring with genetic problems that can reduce the odds of both survival and fertility. New research by a multi-institution team featuring several Texas A&M University biologists has identified the genetic cause of the skin cancer melanoma in the hybrid offspring of two species of swordtail fish, leading to possible new therapies for treating cancer in humans.

In addition to showing that melanoma cases only developed in natural hybrids of sheepshead and highland swordtails, as opposed to the parent species, the team’s research zeroed in on two interacting genes, xmrk and cd97, as the cause of this hybridization-derived melanoma. Their findings are published in the May 14 issue of Science.

“Though these sorts of interactions have long been theorized, this study represents only the second known case in vertebrates where the underlying genes have been clearly identified,” said 2019 Texas A&M biology Ph.D. graduate Daniel Powell, lead author of the team’s paper and a current postdoctoral fellow in the laboratory of Stanford University biologist and Howard Hughes Medical Institute Hanna H. Gray Fellow Molly Schumer. “Interestingly, both the genes we identify have known cancer roles in mammals.”

Texas A&M biology graduate student Mateo García-Olazábal is second author on the paper, which Texas A&M biologist Gil Rosenthal describes as the fruit of a longstanding collaboration with Schumer that began when she was a graduate student at Princeton University and his co-advisee. In addition to Powell and Garcia-Olazabal both being members of his Texas A&M Department of Biology laboratory, Rosenthal established the central Mexico field station that served as the center of the team’s field work. Today, the Centro de lnvestigationes Cientificas de las Huastecas “Aguazarca,” also known as CICHAZ, is supported by funding from both Texas A&M and Stanford, in addition to other sources.

Rosenthal notes that scientists have learned a lot from swordtails — whose hybrids vary by colors, spot patterns, dorsal fin shapes and tail fin extension lengths — and their cousins through the years concerning the genes involved in melanoma, the most common type of cancer worldwide affecting 1 in 50 Americans.

“Here, our insight into the genetics of cancer comes from natural variation in pigmentation genes,” Rosenthal said. “The really powerful thing here is that evolution tells us which cancer genes are under strong natural selection and therefore should be functionally important.”

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