Greenlandic Inuit show genetic signatures of diet and climate adaptation

The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.

Previous studies have attempted to understand the genetic basis of human adaptation to local environments, including cold climates and a lipid-rich diet (1). A recent study found evidence that a coding variant inCPT1A, a gene involved in the regulation of long-chain fatty acid, has been the target of strong positive selection in native Siberians, possibly driven by adaptation to a cold climate or to a high-fat diet (2). Another study found evidence that adaptation to the traditional hypoglycemic diet of Greenlandic Inuit may have favored a mutation in TBC1D4 that affects glucose uptake and occurs at high frequency only among the Inuit (3). However, knowledge about the genetic basis of human adaptation to cold climates and lipid-rich diets remains limited.

Motivated by this, we performed a scan for signatures of genetic adaptation in the population of Greenland. The Inuit ancestors of this population arrived in Greenland less than 1000 years ago (4), but they lived in the Arctic for thousands of years before that (5). As such, they have probably adapted to the cold Arctic climate and to their traditional diet, which has a high content of omega-3 polyunsaturated fatty acids (PUFAs) derived from seafood (6) and a content of omega-6 PUFAs that is lower than in Danish controls (7).




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