A Gene Involved in Non-Shivering Thermogenesis Has Been Under Selection in Greenland Inuit

Greenland Inuit are adapted to an environment characterised by extreme cold; a 2015 study found that a gene involved in non-shivering thermogenesis is likely to have been under selection in this population

In several recent posts, I have discussed the phenomenon of adaptive thermogenesis in humans (i.e., facultative production of heat to maintain body temperature). Under mild cold exposure, signals from the SNS simulate the mitochondria within brown fat cells to produce heat via activation of UCP-1— a process known as non-shivering thermogenesis.

Today, I came across a 2015 paper by Fumagalli et al. (published in Science), which carried out a genetic analysis of 191 Greenland Inuit that had less than 5% European ancestry. The aim of the paper was to look for genetic signatures of adaptation to an environment characterised by extreme cold, and a diet rich in protein and fat (particularly PUFAs).

The authors began by calculating the population branch statistic (PBS) for a sliding windows of 20 SNPs, all the way along the genome. This statistic quantifies, for a particular locus, how genetically different a certain population is from two reference populations. (The formula for PBS can be found in the supplement to this paper.) The basic idea is that natural selection is likely to have taken place within a population if that population is much more genetically different from the two reference populations than they are from one another.

For example, looking at Panel B in the diagram below, GI denotes Greenland Inuit, CEU denotes European Americans (from Utah) and CHB denotes Han Chinese (from Beijing). The branching diagram at the bottom corresponds to the average branch lengths across the entire genome, while the branching diagram at the top corresponds to the average branch lengths for loci with PBS values above the 99.9th percentile (the upper red-dotted line in Panel A). This means that, for the loci in question (e.g., TBX15, WARS2, FADS1 etc.), Greenland Inuit are much more genetically different from European Americans and Han Chinese than those two populations are from one another.

Among the genes with high PBS values, TBX15 is reportedly involved in non-shivering thermogenesis. For example, in a 2012 paper, Gburcik et al. found that reducing the expression levels of TBX15 in mouse pups led to lower expression levels of both adipogenenic markers and brown phenotypic markers. These authors conclude that “TBX15 may be essential for the development of the adipogenic and thermogenic programs in adipocytes/adipomyocytes capable of developing brown adipocyte features.”

In the future, it will be interesting to see whether other cold-adapted populations show evidence of positive selection for genes involved in non-shivering thermogenesis.