Archaic adaptive introgression / Specific Evidence

HHS Public Access Published online 2015 May 12

Evidence for archaic adaptive introgression in humans

This article provides technical info re: specific introgression calculations and locations. The following paragraphs are but a brief example.


In region p21.31 of chromosome 3, there is a 200kb haplotype of Neanderthal origin that has a high frequency (> 49%) in the East Asians sequenced as part of the 1000 Genomes Project7. The introgressed region shows very high LD and significantly high values of the iHS statistic49, which measures extended haplotype homozygosity and is a hallmark of a recent selective sweep. However, as mentioned before, it is unclear how the iHS score would be affected by admixture in the absence of selection. One of the most likely targets of selection is a nonsynonymous SNP in the gene HYAL2, involved in the cellular response to ultraviolet radiation. The SNP is absent in other non- African populations, so it appears to have been lost in the ancestors of Eurasians after migrating out of Africa, but was regained in East Asians via admixture with Neanderthals. The authors performed a bootstrapped phylogenetic analysis to support the shared ancestry of the haplotype with the Neanderthal sequence and obtained a significant p-value for the observed LD value compared to a null model without introgression. Its frequency distribution shows a weak latitudinal gradient, suggesting it was involved in the adaptive response to ultraviolet radiation as modern humans expanded throughout Asia7. A putative signal of adaptive introgression in East Asians in HYAL2 has also been identified using the CRF framework47.

BNC2 seems to be a strong candidate for adaptive introgression, as shown in two genome-wide archaic ancestry analyses23, 47. Sankararaman et al.47 applied the CRF model to detect introgressed segments, and then inferred selection based on departures from a null model of neutrally introgressed alleles. Vernot and Akey23 also found the introgressed region using S*, then confirmed its ancestry by matching it with the Neanderthal genome, and finally inferred selection by observing that the region has high differentiation between Europeans and Asians, as measured by FST. A BNC2 SNP is associated with skin pigmentation76 and freckling in Europeans77, and the archaic haplotype is present at 70% frequency in Europeans, while it is absent in Asians. Interestingly both studies also found a strong adaptive introgression signal in a cluster of keratin genes on chromosome 12 in both Asians and Europeans23, 47.

Two neighboring genes (POU2F3 and TMEM136) have significant evidence for adaptive introgression in East Asians only, again based on the two genome-wide archaic ancestry analyses23, 47 (see above). POU2F3 is a transcription factor that mediates keratinocyte differentiation and proliferation, and the archaic haplotype is at 66% frequency in East Asians but almost absent in Europeans. TMEM136 codes for a transmembrane protein, but little information is available about its function.47


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