Is hating the heat (or cold) genetic?
Some like it hot
It’s been a bit hot recently. For those of you who don’t live here in Perth, Western Australia, we have had a record-breaking summer, suffering through 7 days over 40 degrees (104oF) in February alone. Generally, I don’t mind the heat, and I do not cope well with the cold, the positive of the 40-degree days is that our pool warms up to the point where it actually feels refreshing rather than pure torture. Still, I can’t feel that as a very white person, with mostly British ancestry, I am also not genetically built for this heat. But what does the science say about the genetics of heat tolerance?
As I alluded to, the most obvious way that genetics influences our ability to cope with different temperatures is through our skin colour, which is a great example of natural selection in action. In hotter climates, dark skin provides an advantage against UV damage, but in cooler climates this can cause vitamin D deficiency. As humans moved out of Africa and into Europe and Asia, mutations causing lighter skin provided an advantage, especially as vitamin D is known to be important for fertility, pregnancy and breastfeeding,1 and so spread (relatively) quickly. These mutations mostly affect the production of melanin, the pigment in the skin produced by cells called melanocytes. There are two types of melanin known to affect skin colour, pheomelanin which is yellow-red and eumelanin which is brown-black. The amount, size and proportion of these two types of melanin is what controls skin colour.
Pretty much everyone with a European background (and pretty much no one else) have a variant in a gene called SLC24A5,2 which codes a protein called sodium/potassium/calcium exchanger 5 (NCKX5) that controls the amount of calcium in the melanosome, the part of the cell where melanin is made and stored. Other gene with variants in Europeans include SLC45A2, TYR, TYRP1, OCA2 and MC1R, while people of East Asian descent also have variants in TYR, TYRP1, OCA2 and MC1R, although these are different variants than those found in Europeans.2 This is an example of what is known as convergent evolution, where independent populations develop similar traits as a result of similar environmental factors, such as similarities in body shape of sharks and dolphins and the development of wings in birds and bats.
All of those genes are thought to be involved in the production of melanin. For example, MC1R codes the melanocortin 1 receptor. This receptor is activated by melanocyte-stimulating hormones which causes melanocytes to switch from producing pheomelanin to producing eumelanin. Mutations in MC1R that stop the receptor from working cause a lack of the dark eumelanin, resulting in very fair skin and red hair.3 Yes, this is the ‘redhead gene,’ and it is recessive, meaning you need two copies of the gene to have red hair. This is what lead to the (untrue) myth that redheads are going extinct, and is why red hair is relatively rare. Interestingly, considering redheads are clearly not suited to hot climates, there is evidence that they also feel the cold more too. Liem, et al.4 put a special probe on the arms of 30 red-haired and 30 dark-haired women and decreased its temperature. The women were instructed to push a button when the cold probe began to feel painful and again when they couldn’t stand the cold anymore. The results were striking; redheads felt cold pain at an average of 22.6oC, compared to 12.6oC for brunettes, and couldn’t tolerate the pain at 6oC, while brunettes could last until 0oC.
So, it seems MCR1 not only affects our skin colour, and therefore our sensitivity to UV damage, but also our perception of temperature. But I’m a brunette, why am I such as wimp when it comes to the cold? It does seem this may be somewhat down to my genes; a twin study concluded that feeling the cold was about two thirds down to genetics, with the last third down to environment.5 One specific gene that seems to impact how much we feel the cold is known by the catchy name of transient receptor potential melastatin 8 (TRPM8). The protein it codes is also known by the more useful name of cold and menthol receptor 1, which describes its function nicely, it detects cold temperatures as well as menthol, which is why menthol can feel cool even when it’s at room temperature. A variant in this gene is found in 88% of people in Finland, but only 5% in Nigeria,6 so it seems this variant also provided an advantage to populations moving out of Africa into colder climates. A variant of a related gene, transient receptor potential melastatin 2 (TRPM2), was found to influence cold hypersensitivity in Japanese women,7 but instead of detecting cold, TRPM2 is activated by warm temperatures. So, these women may not be necessarily hypersensitive to the cold, but instead may quicker to lose the feeling of warmth due to a defect in their heat perception.
So, it seems that our ability to cope with different temperatures is indeed down to our genes, with a bit of environment thrown in. In fact, it is a great example of how humans have and will continue to evolve, and a great bit to mention to people who don’t believe in natural selection.
References
1. Pilz S, Zittermann A, Obeid R, et al. The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. Int J Environ Res Public Health 2018;15(10) doi: 10.3390/ijerph15102241 [published Online First: 2018/10/17]
2. Deng L, Xu S. Adaptation of human skin color in various populations. Hereditas 2018;155:1. doi: 10.1186/s41065-017-0036-2 [published Online First: 2017/07/14]
3. Barsh GS. What controls variation in human skin color? PLoS Biol 2003;1(1):E27. doi: 10.1371/journal.pbio.0000027 [published Online First: 2003/10/14]
4. Liem EB, Joiner TV, Tsueda K, et al. Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. Anesthesiology 2005;102(3):509-14. doi: 10.1097/00000542-200503000-00006 [published Online First: 2005/02/26]
5. Chae J-H, Chung KW, Hur Y-M, et al. Feeling of Cold Hands and Feet is a Highly Heritable Phenotype. Twin Research and Human Genetics 2012;15(2):166-69. doi: 10.1375/twin.15.2.166 [published Online First: 2012/03/28]
6. Key FM, Abdul-Aziz MA, Mundry R, et al. Human local adaptation of the TRPM8 cold receptor along a latitudinal cline. PLoS Genet 2018;14(5):e1007298. doi: 10.1371/journal.pgen.1007298 [published Online First: 2018/05/04]
7. Wu X, Yoshino T, Maeda-Minami A, et al. Exploratory study of cold hypersensitivity in Japanese women: genetic associations and somatic symptom burden. Scientific Reports 2024;14(1):1918. doi: 10.1038/s41598-024-52119-y