Incidence of ancient variants associated with oncological diseases in modern populations

Abstract

Publicly available genome-wide data, sequenced from 2730 ancient human samples were analyzed for genetic predisposition to malignancy. The temporal and spatial incidence of risk variants for cancer diseases in ancient genomes was recorded, allowing for estimates of their frequencies in ancient human communities. We identified 55 risk alleles associated with oncological conditions in the screened ancient samples. For further analysis, we selected three variants conclusively deemed to entail pathogenic effect, the VHL gene’s rs28940298, the TP53 gene’s rs78378222 and the BRCA2 gene’s rs11571833. The contemporary population frequency of these three variants is lower, or similar, to their estimated frequency in ancient human communities, indicating that they might have been subject to negative selection. This is also suggested by their temporal dynamics during the last 10000 years, which show an overall temporal decrease in population frequency. The oldest samples in which these three variants were established testify their ancient origin, including the presence of TP53 gene’s rs78378222 variant in 50000 BP old Neanderthal and Denisovan genomes. Our results demonstrate the presence of cancer-causing mutations in ancient human communities and suggest that they differed in frequency among ancient populations as they do among contemporary ones. Data on germline mutations in tumour suppressor genes in ancient human genomes are scarce and their historic prevalence gives insights into the evolution of predisposition to cancer disease and hence helps advance paleogenomic medicine.

Keywords:

• Ancient DNA
• genome-wide data
• variants associated with cancer
• VHL gene
• TP53 gene
• BRCA2 gene

Data availability

Genome-wide data used for this study are publicly available from Allen Ancient DNA Resource 2021, version 50.0, https://reich.hms.harvard.edu/allen-ancient-dna-resource-aadr-downloadable-genotypes-present-day-and-ancient-dna-data. Datasets used for the analyses are given in the Supplementary material S1 and S2. Any additional data used to support the findings of this study are available from the corresponding author upon request.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

The authors received no specific financial support for the present research.