Abstract
Mitochondrial DNA variants associated with diseases are widely studied in contemporary populations, but their prevalence has not yet been investigated in ancient populations. The publicly available AmtDB database contains 1443 ancient mtDNA Eurasian genomes from different periods. The objective of this study was to use this data to establish the presence of pathogenic mtDNA variants putatively associated with mitochondrial diseases in ancient populations. The clinical significance, pathogenicity prediction and contemporary frequency of mtDNA variants were determined using online platforms. The analyzed ancient mtDNAs contain six variants designated as being "confirmed pathogenic" in modern patients. The oldest of these, m.7510T>C in the MT-TS1 gene, was found in a sample from the Neolithic period, dated 5800-5400 BCE. All six have well established clinical association, and their pathogenic effect is corroborated by very low population frequencies in contemporary populations. Analysis of the geographic location of the ancient samples, contemporary epidemiological trends and probable haplogroup association indicate diverse spatiotemporal dynamics of these variants. The dynamics in the prevalence and distribution is conceivably result of de novo mutations or human migrations and subsequent evolutionary processes. In addition, ten variants designated as possibly or likely pathogenic were found, but the clinical effect of these is not yet well established and further research is warranted. All detected mutations putatively associated with mitochondrial disease in ancient mtDNA samples are in tRNA coding genes. Most of these mutations are in a mt-tRNA type (Model 2) that is characterized by loss of D-loop/T-loop interaction. Exposing pathogenic variants in ancient human populations expands our understanding of their origin and prevalence dynamics.
Highlights
The scarcity of prehistoric human remains hampers obtaining complete picture of disorder incidence in ancient times
Out of 3191 unique mtDNA variants established in the 1443 analyzed ancient samples, six are designated as being “confirmed pathogenic” and 10 as likely/possibly pathogenic by MitoMap
The variant m.5703G>A was found in four ancient mtDNA samples, one from the Neolithic period, three from the Iron Age and one from the Middle Ages
Summary
The scarcity of prehistoric human remains hampers obtaining complete picture of disorder incidence in ancient times. Neoplastic tumors have been detected in early Homo samples as old as 1.7 million years ago, and these provide further insight into the outset of human cancers [6]. Mummified human remains of a 5300-year-old Neolithic man Based on information on subsistence, geography and sample age, Berens et al (2017) estimate the genetic disease risk for 3180 loci in 147 ancient genomes, and find it to be similar to that of modern day humans [8]. They estimate that the overall genomic health of the Altai Neanderthal is worse than 97% of present day humans and that Ötzi the Tyrolean
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