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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 …