Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals

Most studies of archaic introgression have relied on the GRCh37 human reference genome.

“However, most studies of archaic introgression have relied on the GRCh37 human reference genome [8, 10, 11, 13, 14, 20].”

Neanderthal ancestry is relatively uniform among modern Eurasian populations but is approximately 8 to 24% higher in East Asia than in Europe.

“While NE ancestry is relatively uniform among modern Eurasian populations (1, 2), it is approximately 8 to 24% higher in East Asia than in Europe (5, 10, 12, 13).”

This second range expansion is essential for explaining the pattern currently observed of lower Neanderthal ancestry in western Europe than in East Asia.

“This second range expansion is essential for explaining the pattern currently observed of lower NE ancestry in western Europe than in East Asia (5, 10, 12, 13).”

The presence of Denisovan-like haplotypes in Africa could result from back-to-Africa migrations.

“The presence of such Denisovan-like haplotypes in Africa could result from back-to-Africa migrations [44] and, as shown by our S prime analysis when using Mbuti as unadmixed group, it might have easily prevented the detection of the SLC30A9 gene in previous maps of archaic introgression in modern humans.”

Some archaic alleles and haplotypes are adaptive and persist at high frequencies in human populations.

“For instance, substantial evidence suggests that some archaic alleles and haplotypes are adaptive and persist at high frequencies in human populations [10, 13–19].”

A recent study that used an outgroup-free method to detect Neanderthal ancestry blocks in human genomes also found a higher average amount of Neanderthal ancestry in African genomes than has been previously reported.

“We note that a recent study that used an outgroup-free method to detect Neanderthal ancestry blocks in human genomes also found a higher average amount of Neanderthal ancestry in African genomes than has been previously reported (20).”

We reject the explanation that excess Neanderthal ancestry in Central and East Asians could be mostly due to underestimating Neanderthal ancestry in West Eurasians as a result of using sub-Saharan Africans, who share some Neanderthal ancestry with West Eurasians, as a model unadmixed outgroup, because removing Neanderthal haplotypes from West Eurasians would likely increase the number of globally?

“We reject this explanation because removing Neanderthal haplotypes from West Eurasians would likely increase the number of geographically restricted Neanderthal haplotypes in Asians, contrary to our observation.”

The Neanderthal ancestry in some African genomes is due to back-migration.

“due to back-migration, consistent with other recent reports (20).”

Compared to previously reported GRCh37 callsets, more Neanderthal sequences per individual were identified in both GRCh38 and T2T-CHM13, with this enrichment being consistent across populations.

“Compared to previously reported GRCh37 callsets [10], we identified more Neanderthal sequences per individual in both GRCh38 and T2T-CHM13, with this enrichment being consistent across populations (Fig. 2C).”

Discordant homozygotes ("2-0" genotype pattern variants) serve as strong evidence against introgression in IBDmix.

“Discordant homozygotes (i.e., variants where the genotype of the archaic individual is homozygous alternative and the modern human genotypes are homozygous reference, referred to as “2–0” genotype pattern variants in “Results”) serve as strong evidence against introgression in IBDmix [10].”

The whole-genome data processing procedures of this study closely align with those of the previous study, with some differences in certain details.

“Our procedures closely align with those outlined in the previous study [10], and also with some differences in certain details”

Other more complex scenarios including a first introgression event from ancestors of modern humans into archaic humans followed by a second archaic introgression event into non-Africans and back to Africa migrations cannot be discarded.

“Similarly, we cannot discard other more complex scenarios including a first introgression event from the ancestors of modern humans into archaic humans followed by a second archaic introgression event into non-Africans and back to Africa migrations, as similarly suggested to explain the finding of Neanderthal introgression sequences in the 1000 GP African populations or the presence of a putative”

Maps produced by SARGE are about as concordant with published maps as the published maps are with each other.

“We found that maps produced by SARGE are about as concordant with the published maps as the published maps are with each other (fig. S25).”

There is substantial overlap among the three reference genomes, with ~94% of the Neanderthal sequences identified in T2T-CHM13 being shared with those previously reported in GRCh37.

“Despite these unique discoveries, we observed substantial overlap among the three reference genomes, with ~ 94% of the Neanderthal sequences identified in T2T-CHM13 being shared with those previously reported in GRCh37 (Fig. 2d) [10].”