A team at the Pennsylvania State University College of Medicine, led by Dr. Keith Cheng, is using two genetically similar indigenous populations on opposite sides of the globe to try to uncover the genetics underlying East Asian skin color mutations, a project which might garner important clues toward gaining an understanding of melanoma susceptibility.
Humans first migrated from Africa to East Asia hundreds of thousands of years ago, gradually evolving a lighter skin color as a result of several genetic mutations. The search for these mutations was launched in 2005, after Dr. Cheng uncovered the key European skin color mutation (Science published the story as a cover article). While East Asians share the trait of light skin with Europeans, Dr. Cheng discovered that they do not carry the same skin color mutations, leading him to infer that their skin color was influenced by different mutations with a similar function.
Compared to Africans, individuals with primarily European ancestry are approximately 20x more susceptible to developing melanoma, a deadly form of skin cancer characterized by unrestrained proliferation of pigmentation cells. Africans are largely protected from the disease by virtue of their darker complexion, while Europeans are much more susceptible due to their lighter complexion. The riddle is that East Asians, who are also light-skinned, develop melanoma at a rate that is almost identical to Africans. “This inconsistency has led us to re-visit our understanding of melanoma and ask if there is another way to approach the problem: by studying the genes of a light-skinned population which, unlike Europeans, is largely unaffected by the disease,” explains Dr. Cheng.
The initial step in this approach is to isolate the first, and most important, of the string of mutations that give East Asians their light complexion. Thus, the hunt began with a search for populations whose genetic makeup is mixed East Asian and West African origin, but excludes the presence of European skin color mutations. The range of skin color in these populations reflects the extent to which this mutation is present, or absent, in individuals. Comparisons of the gene sequences between individuals will enable the team to identify the primary East Asian skin color mutation.
The team found such a population among the Orang Asli, the indigenous people of Peninsular Malaysia. In 2009, Dr. Khai C. Ang, a postdoctoral fellow under Dr. Cheng, collected 371 blood samples from the Senoi, one of three subtribes of the Orang Asli. Ang’s preliminary findings were published this past spring in the journal PLOS ONE.
Using the Orang Asli data, the team was able to begin identifying potential candidates for the mutation. In order to narrow the possibilities and confirm that the identified mutation is sufficiently widespread and ancient in origin, the team is studying a second indigenous tribe, the Kalinago of the Commonwealth of Dominica. This tribe is ideally suited to mutually validate the findings, presenting a similar ancestral background to the Senoi in a locale half a world away.
To fund this new sampling endeavor, the team is experimenting with a platform that is relatively novel for scientists: on-line crowdfunding, (i.e. Kickstarter and Indiegogo) through which the public can contribute directly to projects they would like to see move forward. Ang and his team launched a campaign through Microryza, a purely scientific platform, on September 30 to raise $15,000: just enough to get them to Dominica to collect their samples, extract the DNA on-site, and fly home again. However, Microryza is an ‘all-or-nothing’ model: pledged money will be collected from contributors only if the fundraising goal has been met by the end of the campaign, January 6, 2014 at 11:59pm PST.
“I never meant to get into skin color research: it happened by accident,” Dr. Cheng says. “But once we found the European mutation, I felt compelled to finish the story. Not just for the sake of understanding our biological roots as humans, but also to try and demystify the idea that skin color is anything more than a chance mutation, spread through natural selection, that enabled humans to populate and thrive in the variety of climatic conditions across the globe.”
If you’d like to ask a question about the project, shoot the team an email: info@chenglab.com. Check out their Microryza project page (Donations are tax-deductible). You can also follow them on Facebook, Twitter and Instagram.
