Fish gene sheds light on human skin colour variation 15/12/05. By Penn State With help from a common aquarium pet – the zebrafish - and the HapMap online database of human genetic variation, researchers have found an important human skin colour gene.

A change in just one amino acid in one gene plays a major role in determining why people of European descent have lighter skin than people of African descent, according to research led by Keith Cheng at Penn State Cancer Institute.

The find could lead to further research using the protein coded by the pigmentation gene as a target for treatment of malignant melanoma, the most deadly form of skin cancer, as well as to research on ways to modify skin colour without damaging it by tanning or using harsh chemical lighteners.

The findings were published as the cover story in the 16 December issue of the journal Science.

Previous studies on pigmentation have identified more than 100 genes involved in pigment production. Alterations in some of these genes are associated with disorders such as albinism, which causes very light skin, but also vision problems. However, most of the genes responsible for normal differences in skin pigmentation remained unknown. The gene identified by Cheng's team - called SLC24A5 -previously had not been suspected to be involved in pigmentation.

The pigmentation discovery was an unexpected offshoot of Cheung's cancer research on zebrafish, which has many genes similar to human genes. Furthermore, pigment cells from both fish and humans contain pigment granules called melanosomes. In people of European descent, the melanosomes are fewer, smaller and lighter than those from people of West African ancestry, while the melanosomes of East Asians show intermediate properties.

Cheng's team found that a zebrafish variant called 'golden' also had fewer, smaller, and less heavily pigmented melanosomes than normal fish. The lighter pigmentation of golden zebrafish was found to be caused by a mutation that cuts short a certain protein – referred to as slc24a5.

Using the recently released HapMap - a free and publicly accessible database of DNA sequence variation in the human genome - the researchers then looked at variations within the human SLC24A5 gene. They found that the protein specified by the gene was identical in all populations studied, except for the amino acid at one position. At that position, West Africans and East Asians shared the same ancestral sequence with other vertebrates, including zebrafish and chimpanzees. In contrast, all individuals in the European population tested showed a change in one amino acid.

According to Mark Shriver at University Park, the results are indicative of a 'selective sweep', which is a signal of selection for a particular gene variant.

Either a variant is selected for because the trait produced is better suited to the current environment than other traits and other traits are less capable of competing, or the variant is sexually selected. Sexual selection occurs because individuals choose mates with certain characteristics that are more attractive or that indicate better reproductive potential.

To verify the importance of the amino acid change, Shriver examined the SLC24A5 gene in populations of mixed European and West African ancestry. Individuals with the European form of SLC24A5 tended to have lighter skin than those with the ancestral form of the gene. Those findings suggested that this variation contributes between 25 to 38 percent of the range of skin colour in this population.

The team speculates that well-known variations in European eye and hair colour may have been made possible by the alteration in SLC24A5. However, they say that the patterns of DNA variation indicate that the lighter skin colour of East Asians is due to variation in genes that have yet to be identified.

Scientists have long hypothesised that decreased skin pigmentation was an adaptive change that made it possible for humans to live outside the tropics, since sunlight is essential to generate the vitamin D required to prevent rickets, a condition causing bones to become weak. Team members suggest that the gene they have identified played an important role in that adaptation in Europeans.

Adapted from a news release by Penn State.

Further reading

Lamason RL, et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science. 2005 Dec 16;310(5755):1782-6. Abstract