Researchers from the University of Utah and Qinghai University in China have discovered two genes which assist ethnic Tibetans survive in the high altitude of the Himalayas. Their study, recently published in the journal Science, compared key genes in 31 unrelated Tibetans to those of 45 lowland Chinese and 45 Japanese people. They found that the EGLN1 and PPARA genes were responsible for the characteristic lower levels of hemoglobin in Tibetans – revealing half the genetic mystery in to what allows them to survive in the thin air. Further research in this field may not only reveal the genes responsible for high-altitude adaptation, it could be the first step in providing the same genetic boon to people all over the world.
Tibetans are not the only ethnic group in the world which has adapted to high altitude conditions, but they do seem to be the only ones that have done so with a low red blood cell count. Most other groups, including mountain-dwelling groups in the Andes, compensate for lower oxygen levels by increasing hemoglobin levels. This does the job very well, but extremely high hemoglobin levels do have associated health risks (i.e. issues with circulation). Tibetans actually have lower than normal hemoglobin levels, indicating that they are using what little oxygen is in their blood very efficiently. By determining which genes cause this lower hemoglobin level, scientists have found the first (perhaps less exciting) half of the Tibetan genetic puzzle.
The Chinese and American researchers isolated the EGLN1 and PPARA genes by carefully narrowing down possibilities. From databases of genetic samples in China, researchers were able to determine 247 genes that were likely to code for oxygen processing. Then they examined the DNA of 45 Chinese, 45 Japanese and 31 unrelated Tibetan individuals and found those variations which were present in Tibetans but not the other two groups. From there, they narrowed the list of possible genes down to those that had the greatest frequency in Tibetans with the lowest hemoglobin counts: EGLN1 and PPARA.
While this study was very thorough, it’s important to note that the research did not use whole genome sequencing. Rather, a SNP array looked at 900,000+ SNPs (single nucleotide polymorphisms) to find the important variants. Data for the Chinese and Japanese individuals came from the HapMap project and were collected before the Tibetans. None of this limits the results of the study, but given the complexity of the gene interactions there may be more to find out using a whole genome sequencing technique.
I should also point out (again) that lower hemoglobin levels are just the first half of the genetic puzzle. And, to be blunt, probably the less useful half. We don’t have a huge need for lowering the oxygen levels in people (at least for now). What we really need to know is how Tibetans are able to live with such low O2 levels and survive. What’s the genetic secret behind the associated oxygen processing efficiency that comes with their lower hemoglobin levels? That’s the second half of the mystery and it will hopefully be solved by the continuing work of these researchers.
We progressive technological types tend to want the best of everything, and genetics is no exception. Finding out which genes code for better oxygen processing in Tibetans is a great scientific question, but I think it’s exciting because finding the answer could lead the way to giving the same benefits to non-Tibetans. Other scientists are trying to find the genes that code for life-long athleticism, and the genes that promote rapid muscle growth. Taken together, this research could lead to optimizing the human body for performance by either changing genes, or (much more likely) finding ways to promote the protein pathways controlled by those genes. In the future we may all be able to pop a pill and run around the Himalayas as if they were Miami Beach. Someone tell the sherpas to start looking for new jobs.