Limited Evidence for Selection at the FADS Locus in Native American Populations

The FADS locus contains the genes FADS1 and FADS2 that encode enzymes involved in the synthesis of long-chain polyunsaturated fatty acids. This locus appears to have been a repeated target of selection in human evolution, likely because dietary input of long-chain polyunsaturated fatty acids varied over time depending on environment and subsistence strategy. Several recent studies have identified selection at the FADS locus in Native American populations, interpreted as evidence for adaptation during or subsequent to the passage through Beringia. Here, we show that these signals are confounded by independent selection-postdating the split from Native Americans-in the European and, possibly, the East Asian populations used in the population branch statistic test. This is supported by direct evidence from ancient DNA that one of the putatively selected haplotypes was already common in Northern Eurasia at the time of the separation of Native American ancestors. An explanation for the present-day distribution of the haplotype that is more consistent with the data is that Native Americans retain the ancestral state of Paleolithic Eurasians. Another haplotype at the locus may reflect a secondary selection signal, although its functional impact is unknown.