Researchers found a zebrafish variety known as golden with lighter-colored stripes more than 20 years ago. In today's edition of the journal Science, a team that includes University of Utah researchers reveals the discovery of the gene responsible for this pigmentation change.
The study also discovered a similar version of the fish pigment gene in humans, lead researcher Keith Cheng said.
Learning how this gene mutates in the striped fish not only helps explain why human skin color varies, it also could provide answers to complex diseases in humans that stem from similar genetic changes. Possible applications range from treating malignant melanoma, a deadly skin cancer, to finding safer ways to tan.
A change in a single amino acid, the basic building block of proteins, can have drastic effects on pigmentation. The gene responsible for churning out these pigment proteins is known as SLC24A5 (named for its role as a solute carrier, not for Salt Lake City).
"It's amazing that a single mutation in one gene influences in a major way human skin color," said Cheng, of Penn State College of Medicine in Hershey, Pa.
While the research spotlights the difference between people of European descent with light-colored skin and those of African descent with dark-colored skin, Cheng views the finding in a different way.
"The work otherwise shows an incredible similarity between all the different people of the Earth, and in fact an incredible similarity between all organisms," he said.
Humanity's oldest ancestors - those who emerged from Africa thousands of years ago - carry the normal version of the pigmentation gene. This is the same version of the gene found in many creatures. At some point in human history, a slight genetic mutation occurred that resulted in people with lightly pigmented skin.
"One of the most ancient differences between the original darkly colored, darkly pigmented humans and lightly pigmented humans really has to do with one very simple biochemical change," said David Grunwald, a University of Utah genetic scientist involved in the study.
This gene does not control the production of pigment in humans or in zebrafish. Instead, the SLC24A5 gene determines how much of the produced pigment is packaged and retained by cells known as melanosomes. People of European descent have fewer, lighter melanosomes than do people of African ancestry.
Researchers have yet to determine how the gene influences pigmentation. But it is not a surprise to scientists that such a small genetic change can lead to big differences, Grunwald said.
Cheng and company did not set out to learn the secrets of human skin color. Instead, the research began as a side project more than a decade ago.
"I was actually trying to establish zebrafish as a model for cancer research," he said.
As a working pathologist, he examined the differences in skin cells from golden zebrafish compared with normal zebrafish. Differences in these fish cells reminded Cheng of those found between people of African descent and people of European descent, Grunwald said.
Research published in today's edition of Science is among the first to make use of the HapMap, a human genetic resource unveiled this summer. he said. The project looked at the subtle genetic differences between various groups, including Africans and Europeans. Utah families provide the genetic material for the European descendents.
Grunwald said U. scientists, including graduate research assistant Michael Jurynec, showed the human version of the gene could create pigment changes in zebrafish. The U. maintains a zebrafish facility that houses about 60,000 zebrafish.
Many of the fish involved in the study descend from the golden zebrafish first discovered in an Oregon pet store more than 20 years ago.
While the study illuminates the slight genetic difference in skin color between people of African or European descent, it does not explain pigmentation in those of Asian descent. Cheng said he would like to be part of the future research to solve that question.
glavine@sltrib.com
