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Fish Helps Solve Mystery of Human Skin Color

December 15, 2005

By Maggie Fox, Health and Science Correspondent

WASHINGTON — A little striped fish has helped scientists begin to solve one of the biggest mysteries in biology — which genes are responsible for differences in human skin, eye and hair color.

The large, international team of scientists reported on Thursday that they had found a gene that makes African zebrafish of a lighter-than-normal color — and say the same gene helps explain the light-colored hair, skin and eyes of many Europeans.

While they stress that they have not found a genetic basis for race, they say just a tiny change in a single amino acid plays a major role in causing the distinctive light European coloring.

The gene is called SLC24A5, Keith Cheng of Pennsylvania State University and colleagues said.

“Our results suggest that SLC24A5 explains between 25 and 38 percent of the European-African difference in skin melanin index,” they wrote in Friday’s issue of the journal Science.

Cheng’s team was originally looking for genes involved in cancer. They were using zebrafish, a favored tool of genetic researchers because they are small, reproduce quickly and are well understood.

They found a gene that appeared to make some zebrafish “golden” — with lighter-than-usual stripes. Under a microscope, the skin of these fish have smaller, fewer structures called melanophores.

In people of European descent, pigment granules called melanosomes are fewer, smaller, and lighter than those from people of West African ancestry. The melanosomes of East Asians fall in between.

This suggested gene variations may be responsible and may be similar in vertebrates — which include fish, mice and people.

UNDERSTANDING MUTATIONS

Scientists know that more than 100 genes are involved in pigment production, so the process is complex. But most of the genes identified so far are found in unusual conditions such as albinism, which causes very light skin and eyes.

“…the genetic origin of the striking variations in human skin color is one of the remaining puzzles in biology,” the researchers wrote.

But researchers have published several maps of the human genome and made them available to anyone. Cheng’s team made use of them.

They zeroed on SLC24A5. Penn State pharmacologist Victor Canfield found that all vertebrates have a version of the gene.

They found that one version appears to be the “base” version and is found in most people of African and East Asian descent. Europeans have a mutant version that differs by only a few letters of the genetic alphabet.

Nearly all Africans and East Asians have an amino acid called alanine in that gene, while 98 percent of Europeans tested had an amino acid called threonine there. Amino acids are the building blocks of the proteins controlled by genes.

The researchers injected the base human version into “golden” zebrafish embryos and found it made them develop into normal dark-striped fish. This clinched the idea that the human gene was the equivalent of the fish gene.

Tests of African-Americans and African-Caribbeans found that the version a person carried of SLC24A5 correlated with their skin color.

But it alone cannot explain the great range of human coloring. “Our estimates of the effect of SLC24A5 on pigmentation are consistent with previous work indicating that multiple genes must be invoked to explain the skin pigmentation differences between Europeans and Africans,” the researchers wrote.

Cheng said the work does more than answer curiosity about the concepts of race and skin tone.

“Working out the details of pigmentation with help from model systems like zebrafish is a great paradigm for seeking understanding of other complex diseases such as diabetes or heart disease,” Cheng said in a statement.


Source: reuters



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