December 15, 2005

Stripy fish helps pinpoint human skin color gene

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - 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

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


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

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.