A genetic variation that predisposes people to migraines may have become common in northern European populations because it also grants them a higher tolerance to cold temperatures, according to a team led by the Max Planck Institute for Evolutionary Anthropology.
The study, published in PLOS Genetics, explains how a mutation that induces a less-than-desirable trait can still be selected for by evolution – it confers a significant advantage that outweighs the bad.
Previous investigations into migraines revealed that individuals harboring a specific single-nucleotide variant in the DNA upstream of a gene called TRPM8 are much more likely to experience the disorder than those who do not, though the mechanism behind this remains unclear. This variation is most often found in Europeans, particularly those from the north than it is in other ethnic groups. While this helps explain why white people are more prone to migraines, the finding intrigued scientists for other reasons.
The TRPM8 gene codes for a type of temperature receptor on nerve cells that fires in response to the magnitude of cold, leading to the sensation of chilliness when moderately activated, and feelings of discomfort and pain when highly activated by a low-temperature environment.
Studies in other mammals proved that species living in cold regions have adapted different versions of TRPM8 to help them cope with their harsh conditions, leading the authors to speculate that the human ability to tolerate cold, without which we would never have been able to colonize northerly climates, likely also comes from a TRPM8 variant. Given the migraine-associated mutation's cold-weather distribution, perhaps this is the one?
An analysis of genome samples taken from sample populations across the world seems to confirm their hypothesis: The variant is more and more prevalent in human populations as the group’s location increases in latitude. Accordingly, the areas with the lowest and highest frequency – Nigeria (only 5 percent) and Finland (88 percent) – also have opposite climates.
Computer modeling suggests that the variation first appeared when early humans were in Africa, yet remained at low levels for thousands of years. Then, according to the authors, “selection began about 26,000 years ago, incidentally coinciding with the last glacial maximum around 26,500 years ago.”
Samples of ancient human DNA shows that by 8,000 to 3,000 years ago, the variation had reached the frequency now seen European populations.
"[T]his study nicely shows how past evolutionary pressures can influence present-day phenotypes," lead author Felix Key said in a statement.
Though it is not entirely clear how the alteration upstream of TRPM8 affects the gene itself, the authors speculate that the variant reduces expression of the receptor protein, leading to a reduced ability of nerves to respond to cold.
How the variation and the TRPM8 receptor itself affects migraines will require future research, though the authors point out that, “[i]nterestingly, migraine leads to increased pain perception of [non-harmful] cold temperature and ingestion of cold water can in some cases trigger migraines, providing possible links between TRPM8’s mediated cold perception and some aspects of migraines.”
Migraines are a not fully understood sensory processing disorder wherein over-excited nerves trigger dilation of blood vessels in the head and neck and a painful inflammatory process.
"Migraine is very common in many geographical areas and less common in others It is known to be genetic to some extent—however, all of the genetic contribution is really not known. In this study, finding that a gene TRPM8 (encoding cold sensitivity) that is also seen in large data sets looking at [single nucleotide variations] in migraine is very interesting," neuro-ophthalmologist and migraine expert Dr Kathleen Digre told IFLScience.