Although Neanderthals are extinct, fragments of their genomes persist in contemporary humans. Here we show that while the genome-wide frequency of Neanderthal-like sites is approximately constant across all contemporary out-of-Africa populations, genes involved in lipid catabolism contain more than threefold excess of such sites in contemporary humans of European descent. Evolutionally, these genes show significant association with signatures of recent positive selection in the contemporary European, but not Asian or African populations. Functionally, the excess of Neanderthal-like sites in lipid catabolism genes can be linked with a greater divergence of lipid concentrations and enzyme expression levels within this pathway, seen in contemporary Europeans, but not in the other populations. We conclude that sequence variants that evolved in Neanderthals may have given a selective advantage to anatomically modern humans that settled in the same geographical areas.

While we find changes in lipid catabolism particular to Europeans at the metabolite concentration and enzyme expression levels, the significance of these changes at the organismal level remains to be investigated. Still, the changes observed at the molecular level provide some clues. Among the seven metabolic categories associated with LCP, 2-lysophosphatidylcholine has been implicated in a number of functions, including reactive oxygen species generation, apoptotic and non-apoptotic death, as well as glucose-dependent insulin secretion32 (Fig. 4b,c). Furthermore, genetic variants linked to obesity (DAVID33, Fisher’s exact test, P<0.01 after multiple testing correction, n=38) hypertriglyceridemia and coronary heart disease, as well as triglycerides and cholesterol levels (DAVID, Fisher’s exact test, P<0.01 after multiple testing correction, n=38) in genome-wide association studies34 show a significant enrichment of LPC genes containing an excess of NLS (Supplementary Table 13). Notably, frequencies of these diseases have been shown to differ between individuals of European descent and other human populations35. These observations support a contribution of Neanderthal genetic variants to the phenotype of contemporary Europeans.