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The Central Siberian Plateau was the last geographic area in Eurasia to become habitable by modern humans after the Last Glacial Maximum (LGM). Through a comprehensive dataset of mitochondrial DNA (mtDNA) genomes retained in the remnats of earlier (“Old”) Siberians, primarily the Ket, Tofalar, and Todzhi, we explored genetic links between the Yenisei-Sayan region and Northeast Eurasia (best represented by the Yukaghir) over the last 10,000 years. We generated 218 new complete mtDNA sequences and placed them into compound phylogenies with 7 newly obtained and 70 published ancient mitochondrial genomes. We have considerably extended the mtDNA sequence diversity (at the entire mtDNA genome level) of autochthonous Siberians, which remain poorly sampled, and these new data may have a broad impact on the study of human migration. We compared present-day mtDNA diversity in these groups with complete mitochondrial genomes from ancient samples from the region and placed the samples into combined genealogical trees. The resulting components were used to clarify the origins and expansion history of mtDNA lineages that evolved in the refugia of south-central Siberia and beyond, as well as multiple phases of connection between this region and distant parts of Eurasia.

Leber's hereditary optic neuropathy (LHON) is a form of disorder caused by pathogenic mutations in a mitochondrial DNA. LHON is maternally inherited disease, which manifests mainly in young adults, affecting predominantly males. Clinically LHON has a manifestation as painless central vision loss, resulting in early onset of disability. Epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients in the Western Siberia population. Known \"primary\" pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53,10% (17/32), m.3460G>A - 21,90% (7/32), m.14484T>C - 18,75% (6/32), and rare m.10663T>C and m.3635G>A represent 6,25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.9444C>T, m.6261G>A, m.9921G>A, m.8551T>C, m.8412T>C, m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.

The Central Siberian Plateau was last geographic area in Eurasia to become habitable by modern humans after the Last Glacial Maximum (LGM). Through comprehensive mitochondrial DNA genomes retained in indigenous Siberian populations, the Ket, Tofalar, and Todzhi - we explored genetic links between the Yenisei-Sayan region and Northeast Eurasia over the last 10,000 years. Accordingly, we generated 218 new complete mtDNA sequences and placed them into compound phylogenies along with 7 newly obtained and 70 published ancient mt genomes. Our findings reflect the origins and expansion history of mtDNA lineages that evolved in South-Central Siberia, as well as multiple phases of connections between this region and distant parts of Eurasia. Our result illustrates the importance of jointly sampling modern and prehistoric specimens to fully measure the past genetic diversity and to reconstruct the process of peopling of the high latitudes of the Siberian subcontinent.

Our data first represent the variety of Leber’s hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in the mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself as painless central vision loss, resulting in early onset of disability. The epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53.10% (17/32), m.3460G>A—21.90% (7/32), m.14484T>C–18.75% (6/32), and rare m.10663T>C and m.3635G>A represent 6.25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.6261G>A, m.8412T>C, m.8551T>C, m.9444C>T, m.9921G>A, and m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.