Genetic history of Cambridgeshire before and after the Black Death

Abstract

The extent of the devastation of the Black Death pandemic (1346-1353) on European populations is known from documentary sources and its bacterial source illuminated by studies of ancient pathogen DNA. What has remained less understood is the effect of the pandemic on human mobility and genetic diversity at the local scale. Here, we report 275 ancient genomes, including 109 with coverage >0.1×, from later medieval and postmedieval Cambridgeshire of individuals buried before and after the Black Death. Consistent with the function of the institutions, we found a lack of close relatives among the friars and the inmates of the hospital in contrast to their abundance in general urban and rural parish communities. While we detect long-term shifts in local genetic ancestry in Cambridgeshire, we find no evidence of major changes in genetic ancestry nor higher differentiation of immune loci between cohorts living before and after the Black Death.

Fig. 1.. Sampling locations and genetic ancestry.

(A) Sampling locations in Cambridgeshire. (B) Zoomed in map of Cambridge. (C) PC plot of 109 later medieval and postmedieval genomes with coverage >0.1× in context of ancient (Roman and Saxon period) and modern (UK Biobank) references, with PC1 and PC2 accounting for 0.165 and 0.07% of total variance explained, respectively. (D) Supervised Uniform Manifold Approximation and Projection (UMAP) cluster analysis using PiC with modern references based on 5-cM LSAI sharing among modern and 108 ancient genomes, including 80 from later medieval period, with coverage >0.2×. (E) Intensity of maximum PiC scores. (F) Transect of time of correlations between the regional PiC vectors. The “Modern” correlation for East Anglia is shown as the correlation between PiC vectors of East Anglia and Bedfordshire/Hertfordshire.

Fig. 2.. UMAP plot of individual connectedness among modern and ancient genomes from Britain.

(A) Density of maximum PiC score values per individual in one of the extracted communities. (B) UMAP coordinates of the medieval and postmedieval genomes (> 0.2× coverage) from Cambridgeshire. Archaeological site codes as shown in Fig. 1. (C) Individual connectedness among modern genomes of the “People of the British Isles” project based on PiC scores of 20 significant communities with more than 10 members extracted from the combined data with the Louvain method (unsupervised cluster analysis). (D) Map showing the color codes by counties for the modern genomes used in the UMAP plot A. (E) UMAP coordinates of the Iron Age/Roman and Saxon period genomes.

Fig. 3.. Kinship, genetic diversity and inbreeding.

(A) Normalized pairwise differences (P0) in autosomal data and X chromosome for later medieval sites with more than five burials. Each individual data point represents a pair of individuals (from a total of 171 individuals with >0.01× coverage tested), the aggregate coverage of which is reflected by the opacity of the color. Boundaries for the first- to third-degree of relatedness for autosomal data were defined as in (3). Error bars with two SEMs are shown for the pairs of first- to third-degree of relatedness only. ** and * correspond to significant differences at P < 0.01 and P < 0.05 by two-tailed t test, respectively. (B) Boxplot of normalized autosomal pairwise differences in four Cambridge medieval sites represented by the largest sample size in this study. Each rectangular data point represents a pairwise comparison of individuals sampled from the same site, normalized (with READ) by the average of all pairwise comparisons made in the pool of all later medieval individuals from Cambridge. The opacity of the rectangular color reflects the aggregate of the coverages of the two individuals. The results of significant (P < 0.01) two-tailed Wilcoxon rank sum test are shown with **. (C) The total lengths of ROH tracks longer than 4 cM in individuals grouped by site, showing highly inbred outliers.

Fig. 4.. Heterozygote density and allele frequency differentiation in the HLA locus.

(A) Distribution of average heterozygote density in 1-Mbp windows of chromosome 6. Gray line shows the density of heterozygous sites at common variant positions with minor allele frequency higher than 0.05 in the HRC imputation panel in chromosome 6 for 50 imputed (>0.1× coverage) pre– and post–Black Death genomes from Cambridge. The orange line highlights windows containing genes in the HLA locus. (B) Scatter plot of Max(F_ST) - maximum F_ST between before and after the Black Death cohorts - and Het density values by 1-Mbp windows of chromosome 6. (C) Het density in the before (n = 31) and after (n = 19) the Black Death cohorts.