Through extended survey of mitochondrial DNA (mtDNA) diversity in the Nganasan, Yukaghir, Chuvantsi, Chukchi, Siberian Eskimos, and Commander Aleuts, we filled important gaps in previously unidentified internal sequence variation within haplogroups A, C, and D, three of five (A-D and X) canonical mtDNA lineages that defined Pleistocenic extension from the Old to the New World. Overall, 515 mtDNA samples were analyzed via high-resolution SNP analysis and then complete sequencing of the 84 mtDNAs. A comparison of the data thus obtained with published complete sequences has resulted in the most parsimonious phylogenetic structure of mtDNA evolution in Siberia-Beringia. Our data suggest that although the latest inhabitants of Beringia are well genetically reflected in the Chukchi-, Eskimo-Aleut-, and Na-Dene-speaking Indians, the direct ancestors of the Paleosiberian-speaking Yukaghir are primarily drawn from the southern belt of Siberia when environmental conditions changed, permitting recolonization the high arctic since early Postglacial. This study further confirms that (1) Alaska seems to be the ancestral homeland of haplogroup A2 originating in situ approximately 16.0 thousand years ago (kya), (2) an additional founding lineage for Native American D, termed here D10, arose approximately 17.0 kya in what is now the Russian Far East and eventually spread northward along the North Pacific Rim. The maintenance of two refugial sources, in the Altai-Sayan and mid-lower Amur, during the last glacial maximum appears to be at odds with the interpretation of limited founding mtDNA lineages populating the Americas as a single migration.

With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes’ intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized.

To fill remaining gaps in mitochondrial DNA diversity in the least surveyed eastern and western flanks of Siberia, 391 mtDNA samples (144 Tubalar from Altai, 87 Even from northeastern Siberia, and 160 Ulchi from the Russian Far East) were characterized via high-resolution restriction fragment length polymorphism/single nucleotide polymorphisms analysis. The subhaplogroup structure was extended through complete sequencing of 67 mtDNA samples selected from these and other related native Siberians. Specifically, we have focused on the evolutionary histories of the derivatives of M and N haplogroups, putatively reflecting different phases of settling Siberia by early modern humans. Population history and phylogeography of the resulting mtDNA genomes, combined with those from previously published data sets, revealed a wide range of tribal- and region-specific mtDNA haplotypes that emerged or diversified in Siberia before or after the last glacial maximum, ∼18 kya. Spatial distribution and ages of the "east" and "west" Eurasian mtDNA haploclusters suggest that anatomically modern humans that originally colonized Altai derived from macrohaplogroup N and came from Southwest Asia around 38,000 years ago. The derivatives of macrohaplogroup M, which largely emerged or diversified within the Russian Far East, came along with subsequent migrations to West Siberia millennia later. The last glacial maximum played a critical role in the timing and character of the settlement of the Siberian subcontinent.

BackgroundInflammatory response plays a key role in the development of insulin resistance (IR) in obesity. Oxidative stress triggers the replication of the mitochondrial genome and division of the organelle. The purpose of this study was to identify the relationship of chemerin and TNF-α with mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (mesentery of the small intestine (Mes), greater omentum (GO) and blood mononuclear cells (MNCs)) in patients with obesity with/without type 2 diabetes mellitus (T2DM).MethodsThe study included 142 obese patients and 34 healthy donors. The samples used for the study were peripheral venous blood (MNCs) and ATs (SAT, Mes and GO). The measurement of mtDNA copy number was done by droplet digital PCR. Quantitative determination of insulin, adiponectin, TNF-α and chemerin in serum/plasma was performed by flow-through fluorometry and commercial ELISA kit. Statistical analysis and graphs were obtained in R Statistical Software (version 3.3.1).ResultsThe increase in body mass index (BMI) was accompanied by an increase in TNF-α production, an increase in mtDNA copy number in SAT and a decrease in mtDNA copy number in MNCs. The negative association between plasma chemerin and mtDNA copy number in the Mes, as well as between mtDNA copy number and chemerin expression in the Mes, in the group with BMI > 40 kg/m2 without T2DM demonstrates the protective effect of chemerin against the development of IR via the regulation of mtDNA copy number in adipose tissues.ConclusionsWe thus speculated the existence of a compensatory mechanism in which leads to the increased number of mtDNA copies under the influence of proinflammatory factors. Based on the obtained data, we propose that reducing mtDNA copy number in cases of morbid obesity without T2DM has a positive effect on carbohydrate metabolism, which may help maintain glucose levels within reference values. Obesity, type 2 diabetes, mtDNA, cytokines, TNF-a, chemerin.