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Comment
. 2025 Feb;638(8051):E19-E22.
doi: 10.1038/s41586-024-08496-5. Epub 2025 Feb 19.

Insufficient evidence for natural selection associated with the Black Death

Alison R Barton #  1 , Cindy G Santander #  2 , Pontus Skoglund  3 , Ida Moltke  2 , David Reich  1   4   5   6 , Iain Mathieson  7
Affiliations
Comment

Insufficient evidence for natural selection associated with the Black Death

Alison R Barton et al. Nature. 2025 Feb.
No abstract available

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1 |
Fig. 1 |. Reported enrichment persists even after permutation to remove any signal that could be due to the Black Death.
a, For 100 permutations of the pre- and post-Black Death labels, the observed P values are plotted in a cumulative density plot for the 99th percentile of enrichment of variants with MAF > 10%. The blue dashed line indicates a cumulative count of 5 of 100 runs, the green dashed line indicates the expected significance threshold of 0.05, and the red solid line shows the P value obtained in the original article. b, A q–q plot for the same P values as in a, showing the inflation over the expected null distribution of P values. c, For 100 iterations approximately matching the sample size and coverage from the original study by downsampling a subset of samples from the 1000 Genomes Project, the observed P values are plotted in a cumulative density plot for the 99th percentile of enrichment of variants with MAF > 10%. Lines represent the same values as in a. d, A q–q plot for the same P values as in c, showing the inflation over the expected null distribution of P values.
Fig. 2 |
Fig. 2 |. Bias in allele frequency estimates based on genotype likelihoods.
a, True values against unbiased maximum likelihood (ML) estimates for simulated read data with an average of 5× coverage simulated for 200 individuals at 30,000 SNPs to match the data observed in Klunk et al.. b, True values against biased estimates computed with the Klunk et al. approach for simulated read data with an average of 5× coverage simulated for 200 individuals at 30,000 SNPs. c, Maximum likelihood estimates against Klunk et al. estimates for 31,799 SNPs included in the analysis with no minimum allele frequency threshold. d, Manhattan plot for FST scan of loci that pass the Klunk et al. filtering criteria using maximum likelihood estimates of allele frequencies (equivalent to figure 2c in Klunk et al.). One variant passes the filtering criteria (but does not pass a Bonferroni correction).
Fig. 3 |
Fig. 3 |. No evidence of selection at rs2549794.
a, Histogram of simulated FST values for 2 samples of 38 and 63 diploid individuals from 2 populations with identical allele frequency of 0.438. The dashed red line shows the reported value for rs2549794. b, Distribution of estimated selection coefficients (ŝ), conditional on passing FST and directionality filters, under a null model of identical allele frequency of 0.438 in all populations assuming diploid coverage in all individuals. c, Estimated frequencies of rs2549794 in the 3 time points from Klunk et al. plus the periods 1,000–2,000 bp and the present day. Dashed lines show present-day frequencies and error bars show approximate 95% confidence intervals that overlap the present-day frequency for all time points except post-Black Death (BD) Denmark.
See this image and copyright information in PMC

Update of

Comment on

  • Evolution of immune genes is associated with the Black Death.
    Klunk J, Vilgalys TP, Demeure CE, Cheng X, Shiratori M, Madej J, Beau R, Elli D, Patino MI, Redfern R, DeWitte SN, Gamble JA, Boldsen JL, Carmichael A, Varlik N, Eaton K, Grenier JC, Golding GB, Devault A, Rouillard JM, Yotova V, Sindeaux R, Ye CJ, Bikaran M, Dumaine A, Brinkworth JF, Missiakas D, Rouleau GA, Steinrücken M, Pizarro-Cerdá J, Poinar HN, Barreiro LB. Klunk J, et al. Nature. 2022 Nov;611(7935):312-319. doi: 10.1038/s41586-022-05349-x. Epub 2022 Oct 19. Nature. 2022. PMID: 36261521 Free PMC article.

References

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