Genome sequence of a 45,000-year-old modern human from western Siberia

Abstract

We present the high-quality genome sequence of a ∼45,000-year-old modern human male from Siberia. This individual derives from a population that lived before-or simultaneously with-the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000-13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 × 10(-9) to 0.6 × 10(-9) per site per year, a Y chromosomal mutation rate of 0.7 × 10(-9) to 0.9 × 10(-9) per site per year based on the additional substitutions that have occurred in present-day non-Africans compared to this genome, and a mitochondrial mutation rate of 1.8 × 10(-8) to 3.2 × 10(-8) per site per year based on the age of the bone.

Figure 1

a) Map of Siberia with major archaeological sites. Triangles: Neandertal fossils; white circle in triangle: Denisovan fossils; blue squares: Initial Upper Palaeolithic sites; orange symbol: Ust’-Ishim. 1: Ust’-Ishim; 2: Chagyrskaya Cave; 3: Okladnikov Cave; 4: Denisova Cave; 5: Kara-Bom; B) Radiocarbon ages of early modern human fossils in Northern Eurasia and the NGRIP δ¹⁸O palaeotemperature record. Specimens in light grey are indirectly dated. H5: Heinrich 5 event, H4: Heinrich 4 event, GI 12: Greenland Interstadial 12. For a more extensive comparison see Figure SI2.1. c–f) The Ust’-Ishim 1 femur. c) lateral view; d) posterior view; e) cross section at the 80 percent level; f) cross section at the midshaft. For other views see Figure S3.1.

Figure 2

A) Principal Components (PC) analysis using 922 present-day individuals from 53 populations and the Ust’-Ishim individual; B) PC analysis using Eurasian individuals and the Ust’-Ishim individual. The percentages of the total variance explained by each eigenvector are given.

Figure 3

Statistics testing whether the Ust’-Ishim genome shares more derived alleles with one or the other of two modern human genomes (X, Y). We compute statistics of the form D (X, Y, Ust’-Ishim, Chimpanzee) using a subset of the genome-wide SNP array data from the Affymetrix Human Origins array and restricting the analysis to transversions. Error bars correspond to three standard errors. Red indicates that the D-statistic is significantly different from 0 (|Z|>2), such that the Ust’-Ishim genome shares more derived alleles with the genome on the right (X) than the left (Y). Ancient genomes are given in italics.

Figure 4

Inferred population size changes over time. “Time” on the X axis refers to the pairwise per-site sequence divergence. If we erroneously assume that Ust’-Ishim lived today, its inferred population size history includes an out-of-Africa-like population bottleneck that is more recent than that seen in present-day non-Africans (red bold curve). By shifting the Ust’-Ishim curve to align with those in present-day non-Africans (blue bold curve), and assuming that the number of mutations necessary to do this corresponds to 45,000 years, we estimate the autosomal mutation rate to 0.38–0.49 × 10⁻⁹/site/year. The times indicated on the top of the figures, are based on this mutation rate.

Figure 5

Regions of Neandertal ancestry on chromosome 12 in the Ust’-Ishim individual and fifteen present-day humans. The analysis is based on SNPs where African genomes carry the ancestral allele and the Neandertal genome carries the derived allele. Homozygous ancestral alleles are black, heterozygous derived alleles yellow, and homozygous derived alleles blue.

Figure 6

Exponentially fitted curves showing the decay of pairwise covariance for variable positions where Africans carry ancestral alleles and the Neandertal genome carries derived alleles.