Journal article
Natural selection exerted by historical coronavirus epidemic(s): comparative genetic analysis in China Kadoorie Biobank and UK Biobank
- Abstract:
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Background
Pathogens have been one of the primary sources of natural selection affecting modern humans. The footprints of historical selection events – “selective sweeps”– can be detected in the genomes of present-day individuals. Previous analyses of 629 samples from the 1000 Genomes Project suggested that an ancient coronavirus epidemic ~ 20,000 years ago drove multiple selective sweeps in the ancestors of present-day East Asians, but not in other worldwide populations.
Results
Using a much larger genetic dataset of 76,719 unrelated individuals from each of the China Kadoorie Biobank (CKB) and UK Biobank (UKB) to identify regions of long-range linkage disequilibrium, we further investigated signatures of past selective sweeps and how they reflect previous viral epidemics. Using independently-curated lists of human host proteins which interact physically or functionally with viruses (virus-interacting proteins; VIPs), we found enrichment in CKB for regions of long-range linkage disequilibrium at genes encoding VIPs for coronaviruses, but not DNA viruses. By contrast, we found no clear evidence for any VIP enrichment in UKB. These findings were supported by additional analyses using saltiLASSI, a selection-scan method robust to false positives caused by demographic events. By contrast, for GWAS signals for SARS-CoV-2 susceptibility (critical illness, hospitalization, and reported infection), there was no difference between UKB and CKB in the number located at or near signals of selection, as expected for a novel virus which has had no opportunity to impact the CKB/UKB study populations.
Conclusions
Together, these results provide evidence of selection events consistent with historical coronavirus epidemic(s) originating in East Asia. These results show how biobank-scale datasets and evolutionary genomics theory can provide insight into the study of past epidemics. The results also highlight how historic infectious disease epidemics can shape the genetic architecture of present-day human populations.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.9MB, Terms of use)
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(Supplementary materials, zip, 1.2MB, Terms of use)
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- Publisher copy:
- 10.1186/s12864-025-11876-4
Authors
+ Wellcome Trust
More from this funder
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 088158/Z/09/Z
- 104085/Z/14/Z
- 212946/Z/18/Z
- 202922/Z/16/Z
+ Cancer Research UK
More from this funder
- Funder identifier:
- https://ror.org/054225q67
- Grant:
- 29186
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MC_U137686851
- MC_UU_00017/1
- MC_UU_12026/2
- MC_PC_14135
- Publisher:
- BioMed Central
- Journal:
- BMC Genomics More from this journal
- Volume:
- 26
- Issue:
- 1
- Article number:
- 943
- Publication date:
- 2025-10-21
- Acceptance date:
- 2025-07-03
- DOI:
- EISSN:
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1471-2164
- Language:
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English
- Keywords:
- Pubs id:
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2134019
- Local pid:
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pubs:2134019
- Deposit date:
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2025-07-04
- ARK identifier:
Terms of use
- Copyright holder:
- Morris et al.
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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