35: Tracing CCR5Δ32 through ancient genomes

This episode summarizes a study that genotyped the CCR5Δ32 deletion in ancient and modern human genomes, compared genotyping methods for low‑coverage ancient DNA, reconstructed CCR5 haplotypes, and modeled the deletion's spatiotemporal frequency and selection history. The work benchmarks HAPI (with informed priors) against GATK and VG, maps haplotype distributions (A,B,C), and infers allele frequency trajectories and selection signals across ancestries and time periods. Key terms: CCR5-delta32, ancient DNA, haplotype, selection, genotyping.

Study Highlights:
The authors developed and benchmarked an HAPI genotyping pipeline tailored for low‑coverage ancient DNA and showed it outperformed GATK and VG when using informed priors, recovering CCR5Δ32 genotypes at very low coverage. They assembled haplotype backgrounds (named A, B, C) with tag SNPs linked to CCR5Δ32 and traced their geographic distributions in ancient samples. Spatiotemporal allele frequency maps and modeling indicate increases in CCR5Δ32 frequency in parts of Europe within the last several thousand years and detect ancestry‑specific signals compatible with recent positive selection. The study also highlights sensitivity to coverage, reference choice, and permissive vs strict filtering when inferring trajectories and selection coefficients.

Conclusion:
Ancient DNA genotyping using haplotype‑aware approaches can reliably recover CCR5Δ32 and its haplotype backgrounds at low coverage, enabling reconstruction of the deletion's geographic spread and suggesting recent, ancestry‑specific increases in frequency consistent with positive selection, while results remain sensitive to coverage and filtering choices.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Tracing the evolutionary history of the CCR5delta32 deletion via ancient and modern genomes

Journal:
Cell

DOI:
10.1016/j.cell.2025.04.015

Reference:
Ravn K, Cobuccio L, Muktupavela RA, et al. Tracing the evolutionary history of the CCR5delta32 deletion via ancient and modern genomes. Cell. 2025;188:3679-3695.e16. doi:10.1016/j.cell.2025.04.015

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/ccr5-delta32-ancient-genomes

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-06-06.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited core scientific claims and methods described in the transcript against the article’s findings and metadata, focusing on CCR5Δ32 biology, haplotype architecture, ancient DNA methodology, origin and selection, geographic distribution, and implications for modern genome editing.
- transcript topics: CCR5Δ32 function and HIV resistance; Haplotype architecture A, B, C and 84 tag SNPs; Ancient DNA genotyping with HAPI priors and low coverage; Origin on the Western Eurasian steppe (~6700 years ago); Karagash evidence; Bronze Age selection window (8000–2000 years BP); European allele-frequency trajectories and Northern Europe ~16% frequency

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
-...