Alaska Native genomes show selection signals potentially linked to life in the Arctic; researchers identified variants in pathways associated with high-latitude conditions

Alaska Native communities have built ways of life around one of the harshest environments on the planet, and their genomes contain signals that may reflect some of the pressures of living there. A 2019 paper, Comparing signals of natural selection between three Indigenous North American populations, published in the Proceedings of the National Academy of Sciences (PNAS), compared genome-wide data from Indigenous populations in Alaska, the southeastern United States and central Mexico. In the Alaskan Arctic population, the researchers found strong signals of selection around HS3ST4, KCNH1 and OCA2. The authors interpreted the pattern as evidence consistent with adaptation to cold and high-latitude environments.

How the Arctic left its mark on the genome

For the analysis, scientists used genetic data from Iñupiat individuals on Alaska's North Slope and compared them with data from two Indigenous populations living in warmer regions. The southeastern US and central Mexico groups showed strong selection signals around genes involved in immune function. The researchers suggested that infectious diseases introduced during European colonisation may have contributed to these selection pressures, although the specific causes of the genetic signals cannot be established from the study alone. The Alaskan population showed a different pattern, with its strongest signals involving HS3ST4, KCNH1 and OCA2.


HS3ST4 encodes a heparan sulfate 3-O-sulfotransferase, an enzyme involved in modifying heparan sulfate. The study identified the gene as one of the strongest selection signals in the Alaskan sample, although its precise biological significance remains unclear. KCNH1 encodes a voltage-gated potassium channel involved in regulating electrical activity in cells. It also showed a strong selection signal, but the researchers did not establish that KCNH1 directly affects fat storage or energy use.

OCA2 is better known for its role in pigmentation. Its relevance to Arctic conditions may be connected to sunlight rather than temperature. High-latitude regions receive less UVB radiation, reducing the amount of vitamin D that skin can produce. Earlier work by Hancock and colleagues found an association between OCA2 variation and winter solar radiation across human populations, providing context for the gene's appearance in the Alaskan analysis.

What the wider comparison reveals

The study found surprisingly little overlap in selection signals between the three populations. The Alaskan sample shared only one signal, involving SLIT2, with the southeastern US population and none with the central Mexico group. The two southern populations, meanwhile, shared several immune-related signals. The researchers suggested that these similarities could reflect comparable disease pressures or more recent common ancestry.

The differences point to distinct evolutionary pressures acting on populations living in different environments. In Alaska, the strongest signals were found around three genes that the researchers considered potentially relevant to adaptation to cold and high-latitude conditions. The authors' pathway analysis, however, did not find significant enrichment of the Alaskan selection signals in metabolic pathways.

The findings also differ from earlier research on Greenlandic Inuit populations, which identified selection around FADS genes involved in fatty-acid metabolism and the TBX15 region, which has been associated with adipocyte differentiation. The strongly selected genes identified in the Alaskan population were different, suggesting that populations exposed to similar Arctic conditions may have experienced selection through different genetic pathways.

The authors emphasise that identifying a selection signal does not by itself establish how a genetic variant affects a physical trait. They call for further functional and phenotypic research to determine the biological significance of the signals identified in the study. In the Alaskan population, the findings provide evidence consistent with adaptation to cold and high-latitude environments, while the precise biological effects of the highlighted genes remain uncertain.