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 today (May 14) in 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 García-Olazábal 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 lnvestigaciones 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.”
Powell says it’s possible that when things go wrong in a cell, either due to hybridization or disease, they go wrong in predictable ways. However, he is quick to note that scientists need look no further than swordtails’ hybridized ancestors to realize the question remains open-ended, likely with a multitude of potential answers.
“For example, hybrids of distant relatives of the fish we study here also get melanoma,” Powell said. “While xmrk is one of the genes that causes this, the second gene is different. This suggests a diversity of genetic causes for similar dysfunctions.
“In future studies, we want to better characterize how survival is reduced for hybrids with melanoma in the wild and in captivity. We also want explore why melanoma is so prevalent in some wild hybrid populations, given that we know it reduces survival. It is possible that larger black spots are attractive to potential mates. Perhaps most importantly though, we want to understand whether these sorts of negative gene interactions occur in repeatable ways in other hybrid systems.”
Texas A&M Hagler Institute for Advanced Study (HIAS) Faculty Fellow and visiting biology professor Manfred Schartl also contributed to the research, along with additional collaborators affiliated with Princeton, Northeastern University, University of Würzburg; Benemérita Universidad Autónoma de Puebla, Harvard University and Harvard Medical School, Columbia University and Texas State University. The team’s work was funded in part by the National Science Foundation (Rosenthal Grant No. LTREB 1354172), the Hagler Institute for Advanced Study (Schartl), the Howard Hughes Medical Institute, L’Oreal for Women in Science and the National Institutes of Health (Schumer Grant No. 1R35GM133774).
Read more on Schumer and the broader story via the Stanford News website.
For additional information on Rosenthal and his research, visit https://swordtail.org/.
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