doi: 10.1038/s41467-021-26503-5.
Refining models of archaic admixture in Eurasia with ArchaicSeeker 2.0
Affiliations
- PMID: 34716342
- PMCID: PMC8556419
- DOI: 10.1038/s41467-021-26503-5
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Refining models of archaic admixture in Eurasia with ArchaicSeeker 2.0
Nat Commun.
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Abstract
We developed a method, ArchaicSeeker 2.0, to identify introgressed hominin sequences and model multiple-wave admixture. The new method enabled us to discern two waves of introgression from both Denisovan-like and Neanderthal-like hominins in present-day Eurasian populations and an ancient Siberian individual. We estimated that an early Denisovan-like introgression occurred in Eurasia around 118.8-94.0 thousand years ago (kya). In contrast, we detected only one single episode of Denisovan-like admixture in indigenous peoples eastern to the Wallace-Line. Modeling ancient admixtures suggested an early dispersal of modern humans throughout Asia before the Toba volcanic super-eruption 74 kya, predating the initial peopling of Asia as proposed by the traditional Out-of-Africa model. Survived archaic sequences are involved in various phenotypes including immune and body mass (e.g., ZNF169), cardiovascular and lung function (e.g., HHAT), UV response and carbohydrate metabolism (e.g., HYAL1/HYAL2/HYAL3), while "archaic deserts" are enriched with genes associated with skin development and keratinization.
© 2021. The Author(s).
Conflict of interest statement
The authors declare no competing interests.
Figures
a Seeking algorithm. The light blue dashed box includes archaic reference genomes, the light green dashed box includes tested non-African human genomes, and the black dashed box includes African reference genomes. Dots in different colors stand for mutations of four different observation states in the HMM. b Matching algorithm. After we got the candidate introgressed sequences, we matched them to the seven topologies and found the best-matched one. Each topology corresponds to introgression for one specific lineage, incomplete lineage sorting, or a false-positive signal. c Reconstructing introgression history. For those introgressed sequences from one specific lineage, the length distribution was used to reconstruct the introgression history. A likelihood ratio test was used to find the most likely number of introgression events (K) and the software estimated introgression time and the proportion of each introgression event. AMH, anatomically modern human.
This figure demonstrates the genomic coverage of archaic introgression in four different continental/regional populations. To eliminate the influence of sample size, we set a minimal introgression frequency threshold of each position as 0.02. Regions with introgression frequency greater than 0.02 were defined as introgression-covered regions. We plotted the introgression-covered regions on the genome, where four different colors stand for the four different continental/regional populations, respectively. Red stands for East Asian populations; light blue stands for European populations; orange stands for South Asian populations; and dark blue stands for the Papuan population. The boxplot shows the total introgression-covered length of Neanderthal and Denisovan ancestry for the four different populations. We also performed a test of introgression “deserts.” We first divided the genome into thousands of 100-kb bins. Then, we obtained the empirical distribution of introgression-covered length. A two-tailed test was performed to find those genomic regions with extremely rare introgression segments. For the detailed statistical method, please refer to Supplementary Note 5. The red shadow indicates the 95% confidence interval and each black dot stands for one introgression “desert.” We also plotted the long “desert” on the genome with two different colors. Purple on the genome stands for “deserts” longer than 10 Mb, and brown stands for “deserts” longer than 5 Mb.
a Average proportions of Denisovan introgression in modern humans. Proportions of >0.2% are presented as 0.2% for visualization. b Average proportions of Neanderthal introgression in modern humans. Proportions of >1.5% are presented as 1.5% for visualization.
a Ancestry-sharing ratio of Denisovan-like introgressed sequences. b Ancestry-sharing ratio of Neanderthal-like introgressed sequences. The heatmap of genomic introgression position shares statistics among worldwide populations. Warm colors indicate more sharing of the introgression position and cold colors indicate less sharing. c Introgression diversity of Denisovan-like introgressed sequences. d Introgression diversity of Neanderthal-like introgressed sequences. The y-axis shows the total introgressed sequence length and the x-axis shows the sample size. To avoid sampling errors, 10,000 permutations were performed. CHB Han Chinese from Beijing, China; CHS Han Chinese from South China; JPT Japanese from Tokyo, Japan; CDX Chinese Dai from Xishuangbanna, China; KHV Kinh from Ho Chi Minh City, Vietnam; CEU Utah residents with Northern and Western European ancestry CEPH collection; GBR British from England and Scotland; IBS Iberian populations in Spain; TSI Tuscans in Italy; FIN Finnish in Finland; GIH Gujarati Indians from Houston, Texas, United States; PJL Punjabi from Lahore, Pakistan; BEB Bengali in Bangladesh; ITU Indian Telugu from the UK; STU Sri Lankan Tamil from the UK.
Migration pathways of H. sapiens are supported by archeological evidence. Translucent red and blue represent possible ranges for contact between archaic and modern humans. The waves, admixture proportions, and dates inferred in our study are labeled in boxes in white. kya thousand years ago.
The brown lines represent the lineages of the first-wave “Out of Africa” migration, the green line represents the second-wave “Out of Africa” migration, and the brown-green line represents the lineages admixed by the two-wave “Out of Africa” migration. Red arrow lines represent the Neanderthal-like introgression events and blue arrow lines represent the Denisovan-like introgression events. Shadow areas of different colors stand for different continents/regions.
a Enrichment of Neanderthal-like (upper panel) and Denisovan-like (lower panel) alleles in the pooled eQTLs of all tissues. Each violin plot shows the ratio between the number of eQTLs in the archaic loci and that in the frequency-matched non-archaic loci. Two subsets of loci were analyzed, including all archaic loci (dark blue) and those with archaic allele frequency ≥10% (light blue). The white dot and the black bar in the center of each violin indicate median and interquartile range of the ratio, respectively. Whiskers are represented in the form of Tukey style. The red dashed line indicates ratio = 1. EUR European, SAS South Asian, EAS East Asian, OCE Oceanian. b Enrichment of the archaic-like alleles for eQTLs in each tissue. The Neanderthal-like alleles (upper panel) and the Denisovan-like alleles (lower panel) were analyzed independently. For each population group, two subsets of loci were analyzed, including all archaic loci and those with archaic allele frequency ≥10%. The yellow-to-red heatmap shows significant P values (P value <0.05 obtained by a one-sided empirical test and corrected using the Benjamini–Hochberg procedure accounting for all tissues; Exact P-values are shown in Supplementary Data 5), which means the proportions of eQTLs in the archaic-like alleles are significantly larger than those in the non-archaic-like alleles. In both plots, the EUR group consists of 503 European samples from CEU, FIN, GBR, IBS, and TSI; The SAS group includes 403 South Asian samples from GIH, ITU, STU, and PJL; The EAS group integrates 405 East Asian samples from CHB, CHS, JPT, and CDX; The OCE group is represented by 30 Papuan samples.
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