A high-coverage Neandertal genome from Vindija Cave in Croatia

Neanderthals had a relatively small effective population size of 2,000-3,000 individuals.

“We find that Neanderthals had a relatively small N e of 2,000-3,000 individuals, in agreement with previous pairwise sequential Markov chain analyses of Neanderthal genomes 1 .”

The introgressing Neanderthal population diverged from the Altai Neanderthal population more than 100 kya, while the Vindija was much closer genetically and geographically.

“The introgressing Neanderthal population diverged from the Altai Neanderthal population more than 100 kya, while the Vindija was much closer genetically and geographically1,53.”

Most humans outside of Africa trace about 2% of their genomes to admixture from Neanderthals, which occurred 50-60 thousand years ago.

“Most humans outside of Africa trace about 2% of their genomes to admixture from Neanderthals, which occurred 50-60 thousand years ago 1 .”

The introgressing Neanderthals were probably from populations separated in time and space from the three high-coverage archaic individuals (DAV).

“Moreover, the introgressing Neanderthals were probably from populations that were separated both in time and space from the three archaic individuals who have so far been sequenced to high coverage-hereafter referred to as DAV (Denisovan, Altai Neanderthal and Vindija Neanderthal) 1,17,18 .”

Analyses of available genome-wide association studies and large-scale biobank data revealed that alleles of Neanderthal ancestry are associated with diverse traits in modern Eurasians.

“Analyses of available genome-wide association studies and large-scale biobank data revealed that alleles of Neanderthal ancestry are associated with diverse traits in modern Eurasians1,3–5.”

Nearly all Eurasians have ~2% Neanderthal ancestry resulting from interbreeding events that occurred shortly after their ancestors left Africa.

“nearly all Eurasians have ~2% Neanderthal ancestry resulting from interbreeding events that occurred shortly after their ancestors left Africa1,2.”

The Altai-matching set contains alleles that originated in the Neanderthal lineage and were likely common among diverse Neanderthal groups given the substantial genetic, geographical, and temporal divergence of the Altai Neanderthal from the introgressing population.

“The Altai-matching set contains alleles that originated in the Neanderthal lineage and were likely common among diverse Neanderthal groups given the substantial genetic, geographical, and temporal divergence of the Altai Neanderthal from the introgressing population1,53.”

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).”

Evidence in favor of hybridization between Neanderthals and modern humans has accumulated during the past decade.

“Evidence in favor of hybridization has accumulated during the past decade (4–6).”

Eurasians are estimated to trace around 2% of their genomes to introgression from archaic humans related to the Vindija Neanderthal.

“Eurasians are estimated to trace around 2% of their genomes to introgression from archaic humans 2 related to the Vindija Neanderthal 1 .”

Both our results and previous studies indicate that the introgressing Neanderthal was closer to the Vindija Neanderthal than the Altai Neanderthal or Denisovan.

“Both our results and previous studies 1 indicate that the introgressing Neanderthal was closer to the Vindija Neanderthal than the Altai Neanderthal or Denisovan.”

Much of the current genetic variation within humans predates the split, estimated at 520 to 630 thousand years ago, between the populations that would become modern humans and Neanderthals.

“Much of the current genetic variation within humans predates the split, estimated at 520 to 630 thousand years (ka) ago (1), between the populations that would become modern humans and Neanderthals.”

The mean TMRCA to Neanderthal across all Neanderthal haplotype blocks in non-African populations is about 74 ka ago, using published corrections for branch shortening in the archaic genomes.

“We detect a mean TMRCA to Neanderthal of about 74 ka ago across all Neanderthal haplotype blocks in non-African populations, using published corrections for branch shortening in the archaic genomes (1).”

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).”

Some loci introgressed from archaic hominins in present-day populations appear to influence disease risk, such as neurological, psychiatric, immunological, dermatological, and dietary disorders, either positively or negatively.

“in present-day populations, some loci introgressed from archaic hominins appear to influence disease risk, such as neurological, psychiatric, immunological, dermatological, and dietary disorders (5, 58), either positively or negatively.”

After modern humans left Africa more than 60,000 years ago, multiple admixture events around 55,000 years ago occurred between modern humans and now extinct archaic humans including Neandertals and Denisovans.

“After modern humans left Africa more than 60,000 years ago, genetic evidence suggests multiple admixture events ~55,000 years [9] between modern humans and now extinct archaic humans including Neandertals [10–12] and Denisovans [13, 14].”

The mutation rate used in demographic simulations is different from that in the original description of the demographic model but concordant with more recent studies that measured divergence between modern and archaic hominins.

“This mutation rate is different from that in the original description of the demographic model but concordant with more recent studies that measured divergence between modern and archaic hominins (1).”