The persistence and loss of hard selective sweeps amid admixture in ancient Eurasians

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 14 sweeps persisted across entire 7,000-year period, indicating strong selective pressure

• Primary Outcome: Detection of 48 total selective sweeps (16 known, 32 novel) in ancient Eurasian populations

• Nnt Or Sensitivity: Domain-adaptive neural network showed improved detection compared to standard methods, though specific sensitivity/specificity not quantified

• Confidence Interval: Not reported

Clinical Application

Research findings rather than clinical intervention - may inform pharmacogenomics and population health strategies Limited direct relevance to Australian clinical practice, though may inform understanding of genetic diversity in immigrant populations and Indigenous Australian genetic distinctiveness Limited direct clinical application - primarily relevant for understanding human evolutionary genetics and population-specific adaptations

Abstract

The extent to which human adaptations have persisted throughout history despite strong eroding demographic events such as admixture, genetic drift, and fluctuations in selection pressures remains unknown. Understanding which adaptations were resilient to such forces may shed light on traits that were important for humans across time. Yet, detecting selection from ancient DNA is challenging due to severe degradation of the data and/or signal. Here we detect selective sweeps using a domain-adaptive neural network (DANN) trained on simulated data and applied to more than 800 ancient and modern Eurasian genomes spanning the last 7,000 y. We show that the DANN can account for simulation misspecification, or discrepancies between simulations and real ancient DNA, improving the ability to detect sweeps in real data compared to standard convolutional neural networks or standard statistics. Application of the DANN to data recovered 16 known sweeps at loci including LCT, HLA, KITLG, and OCA2/HERC2, and revealed 32 novel sweeps. All identified sweeps were classified as hard, consistent with historically low population sizes. While some sweeps were lost over time, 14 sweeps at loci involved in functions including neuronal, reproductive, pigmentation, and signaling traits persisted from the earliest to the most recent time periods. In most cases, the most frequent haplotype remained at high frequency across time. Together, these results indicate that hard sweeps predominated in ancient Eurasians and that several ancient selective events were resilient to strong admixture events.