The Plague, also known as the Black Death, killed approximately 75-200 million Europeans, therefore it is not surprising that it is hypothesized that it had an effect on the genetic ancestry of people that lived after the Black Death. Surprisingly, no evidence was found to support this hypothesis!
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The researchers were interested in the effect of the Black Death on the genetic variation in Cambridgeshire. The Black Death, also known as the Second Plague Pandemic, is a plague pandemic caused by Yersinia pestis. It affected Cambridge in 1349. Its death toll in Europe is estimated to be around 30 to 65% of Europe’s population. An evolutionary force known as selective pressure could have produced resistance to the plague. Selective pressure is an external force that influences the survival of individuals in a population, creating evolutionary changes in the traits of that population as time passes. Selective pressure can lead to adaptation which can contribute to shaping human genetic variation.1 It is possible that individuals that survived developed a genetic adaptation that increased their chances of survival against the plague. The Black Death could affect genetic ancestry because it could have resulted in selective pressure in the population. Individuals with genetic variations acquired as a result of selective pressure would have higher survival and reproduction rates, passing down these favorable traits to their offspring as the advantageous alleles become more common in the population.
The researchers sequenced the genome of skeletal remains retrieved from burial sites in Cambridgeshire. Sequencing historical genomes involves extracting and analyzing DNA from ancient remains and it is important for several reasons. It provides valuable information about the past such as the understanding of evolution, population dynamics, diseases, phenotypic variation, etc.2 Sequencing this data can assist in constructing history in relation to the Black Death and other aspects of later medieval life. A genome is all the genetic information of an organism. Sequencing is the process of determining the order of nucleotides within a DNA segment. Sequencing makes it possible for scientists to obtain information about genes, genetic variants, etc. Sequencing a genome involves determining the DNA sequence of an organism’s genetic material.
There are several ways to sequence a genome, in this study whole-genome shotgun sequencing was utilized. Whole genome shotgun sequencing involves randomly breaking up the DNA of an organism’s genome into smaller fragments, sequencing those fragments, then using technology to assemble the sequenced fragments into a whole genome sequence. The researchers extracted aDNA (ancient DNA) from 275 ancient genomes obtained from individuals buried in later medieval and postmedieval Cambridgeshire. The burial sites the bodies were retrieved from represented individuals from different social classes as well as different causes of death.
Whole-genome shotgun sequencing was used because it sequences the entire genome. It can identify structural variants including insertions, deletions, duplications, etc which play a role in genetic diversity. The mean coverage of the genomes was 0.228. 190 genomes had a coverage greater than 0.01x, 143 genomes had coverage greater than 0.05x, and 109 genomes had coverage greater than 0.1x. Coverage can also be referred to as depth, and it is the average number of times a nucleotide in the DNA is read during the sequencing process. Higher coverage indicates that a region has been sequenced multiple times, improving the accuracy and the detection of mutations. In order to examine the effect of the Plague on the genetic diversity of Cambridge medieval population, the researchers estimated heterozygosity and nucleotide diversity genome-wide in the human leukocyte antigen (HLA) locus in the genomes.3 Genome-wide heterozygosity refers to the genetic variation within an individual’s genome; the HLA locus plays an important role in the immune system. Genome-wide heterozygosity and nucleotide diversity could have been influenced by the high mortality rate as it could have reduced diversity across loci. The results of this study showed that due to the long-term effect of balancing selection (a type of natural selection that maintains genetic diversity within a population) on the HLA locus, the region has higher rates of heterozygosity at common genetic variants and there is increased nucleotide diversity. However, the “before” and “after” Black Death individuals do not exhibit higher than average allele frequency differentiation within the HLA region, nor notable differences in the heterozygote density.4 Therefore, no significant differences were observed in heterozygote density in the HLA region when comparing individuals that lived before and after the Black Death.
There are several ethical implications regarding the study of historical genomes, a crucial one is respect for the dead. Studying ancient genomes involves doing research on people who are not able to give informed consent because they are dead. It is also possible that these individuals had cultural and religious beliefs that are being disregarded by studying their remains. Strengths of the study include the use of whole genome shotgun sequencing because it can detect structural variations and the entire genome was able to be sequenced. A weakness of the study is cross-contamination with human DNA with the aDNA, although it is basically impossible to avoid this, it can still have a negative effect on the results. Follow up research can be done on whether descendants of people in areas affected by the Black Death have variation in their HLA regions compared to people from locations where the Black Death was not observed.
References
1) Matteo Fumagalli ,Manuela Sironi,Uberto Pozzoli, et al., 2011. Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Pressure through Human Evolution. https://doi.org/10.1371/journal.pgen.1002355
2) Rowe, Kevin C., Sonal Singhal, Matthew D. Macmanes, Julien F. Ayroles, et al.,”Museum genomics: low‐cost and high‐accuracy genetic data from historical specimens.” Molecular Ecology Resources 11, no. 6 (2011) https://doi.org/10.1111/j.1755-0998.2011.03052.x
3,4) Hui, Ruoyun, Christiana L. Scheib, Eugenia D’Atanasio, et al. “Genetic history of Cambridgeshire before and after the Black Death.” Science Advances 10, no. 3 (2024).DOI: 10.1126/sciadv.adi5903
© Copyright 2022
Department of Biology, Davidson College, Davidson, NC 28036
Shalom Olugbodi
sholugbodi@davidson.edu
I found your article really interesting, Shalom! I think it is very important to restudy major health outbreaks as it can further our knowledge in current health outbreaks such as Covid 19. I like how you included where these individuals were retrieved from and emphasized that they were from different social classes. Additionally, I think partially why the results showed no major significant differences in the heterozygote density could be due to the low coverage of the genomes, as the majority was less than .2x. For your views, I agree that cross-contamination may be a vulnerability since ancient DNA is so difficult to work with. Future research on the black plague should undoubtedly occur when new technologies become available.
Very interesting read, the article provided fascinating insights into the genetic impact of the Black Death on the population of Cambridgeshire through the analysis of aDNA. I really appreciated your mini-paragraph providing a brief summary of Whole-genome shotgun sequencing as I believe that’s extra bit of explanation really helps a lay audience to understand the complexities of this study. The results of the sequencing honestly surprised me, I was expecting some type of significant difference in heterozygosity density in the HLA region before and after the Black Death as I would assume the ones who lived through it would have seen some immune system adaptation acquired. For your views, I agree that it is both important to recognize the benefits of analyze the genomes of dead people to get a better understanding of past diseases and their impact on a populations. I also agree that while its important, there is a slew of ethical questions in regards to unearthing the remains of someone’s ancestors.
And to tag on something else, alike Jomonzon mentioned above, looking at the effects of ancient plagues seems especially smart having lived through the global pandemic of COVID.