Genetic history of the Koryaks and Evens of the Magadan region based on Y chromosome polymorphism data.

In order to clarify the history of gene pool formation of the indigenous populations of the Northern Priokhotye (the northern coast of the Sea of Okhotsk), Y-chromosome polymorphisms were studied in the Koryaks and Evens living in the Magadan region. The results of the study showed that the male gene pool of the Koryaks is represented by haplogroups C-B90-B91, N-B202, and Q-B143, which are also widespread in other peoples of Northeastern Siberia, mainly of Paleo-Asiatic origin. High frequency of haplogroup C-B80, typical of other Tungus-Manchurian peoples, is characteristic of the Evens of the Magadan region. The shared components of the gene pools of the Koryaks and Evens are haplogroups R-M17 and I-P37.2 inherited as a result of admixture with Eastern Europeans (mainly Russians). The high frequency of such Y chromosome haplogroups in the Koryaks (16.7 %) and Evens (37.8 %) is indicative of close interethnic contacts during the last centuries, and most probably especially during the Soviet period. The genetic contribution of the European males' Y chromosome significantly prevails over that of maternally inherited mitochondrial DNA. The study of the Y chromosome haplogroup diversity has shown that only relatively young phylogenetic branches have been preserved in the Koryak gene pool. The age of the oldest component of the Koryak gene pool (haplogroup C-B90-B91) is estimated to be about 3.8 thousand years, the age of the younger haplogroups Q-B143 and N-B202 is about 2.8 and 2.4 thousand years, respectively. Haplogroups C-B90-B91 and N-B202 are Siberian in origin, and haplogroup Q-B143 was apparently inherited by the ancestors of the Koryaks and other Paleo-Asiatic peoples from the Paleo-Eskimos as a result of their migrations to Northeast Asia from the Americas. The analysis of microsatellite loci for haplogroup Q-B143 in the Eskimos of Greenland, Canada and Alaska as well as in the indigenous peoples of Northeastern Siberia showed a decrease in genetic diversity from east to west, pointing to the direction of distribution of the Paleo-Eskimo genetic component in the circumpolar region of America and Asia. At the same time, the Evens appeared in the Northern Priokhotye much later (in the XVII century) as a result of the expansion of the Tungusic tribes, which is confirmed by the results of the analysis of haplogroup C-B80 polymorphisms.

Evaluating the role of selection in the evolution of mitochondrial genomes of aboriginal peoples of Siberia.

Studies of the nature of mitochondrial DNA (mtDNA) variability in human populations have shown that protein-coding genes are under negative (purifying) selection, since their mutation spectra are characterized by a pronounced predominance of synonymous substitutions over non-synonymous ones (Ka/Ks < 1). Meanwhile, a number of studies have shown that the adaptation of populations to various environmental conditions may be accompanied by a relaxation of negative selection in some mtDNA genes. For example, it was previously found that in Arctic populations, negative selection is relaxed in the mitochondrial ATP6 gene, which encodes one of the subunits of ATP synthase. In this work, we performed a Ka/Ks analysis of mitochondrial genes in large samples of three regional population groups in Eurasia: Siberia (N = 803), Western Asia/Transcaucasia (N = 753), and Eastern Europe (N = 707). The main goal of this work is to search for traces of adaptive evolution in the mtDNA genes of aboriginal peoples of Siberia represented by populations of the north (Koryaks, Evens) and the south of Siberia and the adjacent territory of Northeast China (Buryats, Barghuts, Khamnigans). Using standard Ka/Ks analysis, it was found that all mtDNA genes in all studied regional population groups are subject to negative selection. The highest Ka/Ks values in different regional samples were found in almost the same set of genes encoding subunits of ATP synthase (ATP6, ATP8), NADH dehydrogenase complex (ND1, ND2, ND3), and cytochrome bc1 complex (CYB). The highest Ka/Ks value, indicating a relaxation of negative selection, was found in the ATP6 gene in the Siberian group. The results of the analysis performed using the FUBAR method (HyPhy software package) and aimed at searching for mtDNA codons under the influence of selection also showed the predominance of negative selection over positive selection in all population groups. In Siberian populations, nucleotide sites that are under positive selection and associated with mtDNA haplogroups were registered not in the north (which is expected under the assumption of adaptive evolution of mtDNA), but in the south of Siberia.

[Topological Conflicts in Phylogenetic Analysis of Different Regions of the Sable (Martes zibellina L.) Mitochondrial Genome].

Phylogenetic analysis of different regions of the mitochondrial genome of the sable showed the presence of several topologies of phylogenetic trees, but the most statistically significant topology is A-BC, which was obtained as a result of the analysis of the mitochondrial genome as a whole, as well as of the individual CO1, ND4, and ND5 genes. Analysis of the intergroup divergence of the mtDNA haplotypes (Dxy) indicated that the maximum Dxy values between A and BC groups were accompanied by minimum differences between B and C groups only for six genes showing the A-BC topology (12S rRNA; CO1, CO2, ND4, ND5, and CYTB). It is assumed that the topological conflicts observed in the analysis of individual sable mtDNA genes are associated with the uneven distribution of mutations along the mitochondrial genome and the mitochondrial tree. This may be due to random causes, as well as the nonuniform effect of selection.

[Phylogenetic relationships among Asiatic salamanders of the genus Salamandrella based on variability of nuclear genes].

Based on sequence variation of three nuclear genome genes (BDNF, POMC, and RAG1), the phylogenetic relationships among Asiatic salamanders of the genus Salamandrella, Siberian salamander (S. keyserlingii) and Schrenk salamander (S. schrenkii), were examined. Both species demonstrated high levels of heterozygosity determined by intraspecific polymorphism. Fixed interspecific differences were revealed at one nucleotide position of the RAG1 gene, and thus the level of interspecific divergence over the three genes constituted only 0.04%. Analysis of the RAG1 polymorphism across the whole range of S. keyserlingii showed that only one gene variant, encoding for modified RAG1 recombinase, had the highest distribution to the north of the Amur region (west and northeast of Siberia). It is possible that the changes in the RAG1 gene in Siberian salamander are of an adaptive nature. However, cases of interspecific hybridization were identified in Jewish autonomous oblast (JAO), which contains one of the range borders between the two Salamandrella species.

[Mitochondrial Genome Variability in the Wolverine (Gulo gulo)].

The nucleotide sequence of an extended mitochondrial genome segment (11473 base pairs in size) was determined in the wolverine (Gulo gulo) from Magadan oblast. Phylogenetic and statistical analyses of mitochondrial DNA (mtDNA) sequences of mustelids showed that the separation of the Gulo phylogenetic branch occurred at the Miocene--early Pliocene (about 5.6 million years ago (MYA)), while the formation of the species G. gulo took place in the Middle Pleistocene (181 and 234 thousand years ago (KYA), according to the results of molecular dating based on the variability of the extended mtDNA segment and the mitochondrial cytochrome b gene, respectively). The molecular data were in agreement with the fossil records for wolverines.

[Episodes of adaptive evolution of mitochondrial genome in Asiatic salamanders (Amphibia, Caudata, Hynobiidae)].

To elucidate the effect of natural selection on the evolution of mitochondrial DNA (mtDNA) in Asiatic salamanders of the family Hynobiidae, nucleotide sequences of 12 protein-coding genes were analyzed. Using a mixed effects model of evolution, it was found that, in spite of the pronounced effect of negative selection on the mtDNA evolution in Hynobiidae (which is typical for the animals in general), two phylogenetic clusters, the West Asian one, represented by the genera Ranodon and Paradactylodon, and North Eurasian one, represented by the genus Salamandrella, were formed under the influence of episodic positive selection. Analysis of protein sequences encoded by the mitochondrial genome also supported the influence of positive selection on the evolution of Hynobiidae at some stages of their cladogenesis. It is suggested that the signatures of adaptive evolution detected in the mtDNA of Hynobiidae were determined by the complex and long-lasting history of their formation, accompanied by adaptation to the changing environment.

Molecular evolution and adaptation of the mitochondrial cytochrome b gene in the subgenus Martes.

Martes species represent a typical example of rapid evolutionary radiation and a recent speciation event. To identify regions of the genome that experienced adaptive evolution, which might provide clues to their functional importance and may be informative about the features that make each species unique, we sought evidence of molecular adaptation in the mitochondrial DNA (mtDNA) cytochrome b gene in the subgenus Martes. Complete sequences of the cytochrome b gene were obtained from 87 samples, including 49 sables, 28 pine martens, and 10 stone martens, and were combined with mtDNA sequences of other true martens, such as M. melampus and M. americana. Analysis of the cytochrome b gene variation in true martens has shown that the evolution of this gene is under negative selection. In contrast, positive selection on the cytochrome b protein has been detected by means of the software TreeSAAP using a phylogenetic reconstruction of Martes taxa. Signatures of adaptive variation in cytochrome b were restricted to the transmembrane domains, which likely function as proton pumps. We compared results of different methods for testing selection and molecular adaptation, and we supposed that the radical changes of the cytochrome b amino acid residues in the subgenus Martes may be the result of molecular adaptation to specific environmental conditions coupled with species dispersals.

[Peculiarities of phosphoglycerate kinase-1 pseudogene evolution in Schrenck salamander (Salamandrella schrenckii Strauch, 1870)].

Processed copies of genes generally evolve in neutral mode as pseudogenes, however, some of them might be important sources of new functional genes. The psiPGK1 pseudogene has been discovered in Schrenck salamander (Salamandrella schrenckii, Amphibia, Caudata, Hynobiidae) via polymerase chain reaction used to amplify the phosphoglycerate kinase 1 gene (PGK1). This pseudogene is an intronless copy of PGK1 gene absent of exon 6. Analysis of psiPGK1 pseudogene polymorphism has demonstrated that it lacks mutations, which results in shifts in the stop codons and reading frames, as well as that the interspecies variation of this pseudogene was inconsistent with the neutral model of evolution. In addition, the pattern of phylogeographic differentiation of the psiPGK1 variants mainly coincides with that observed in mitochondrial DNA. These observations allow it to be suggested that the psiPGK1 pseudogene is a new functional gene in the Schrenck salamander.

[Population structure of Volga Tatars inferred from the mitochondrial DNA diversity data].

The data on mitochondrial DNA (mtDNA) variation in two populations of Volga Tatars, representing the population of Buinsk and Aznakaevo districts of the Republic of Tatarstan are presented. Comparative analysis of the data on mtDNA variation in the populations of Eastern Europe showed that Volga Tatars were characterized by low interpopulation differentiation (F(ST) = 0.33%), while the level of interethnic differentiation in Eastern Europe is 1.8%. Genetic similarity of Tatars from the eastern regions of Tatarstan to Bashkirs, as well as of Tatars from western regions to Chuvashes, with whom they share territorial borders, was revealed. Positive correlation between population genetic structure in Eastern Europe and linguistic affiliation of the ethnic groups studied was observed.

[Intraspecific structure of sable Martes zibellina inferred from nucleotide variation of the mitochondrial DNA cytochrome b gene].

A fragment of the mitochondrial DNA (mtDNA) cytochrome b gene was sequences in sable from Magadan oblast, Khabarovsk krai, and Kamchatka. Using phylogenetic analysis, the presence of two clusters (A and BC), with the divergence value of 1.4%, was demonstrated. Analysis of the cytochrome b gene median networks indicated that split of the ancestral population took place in early Pleistocene (about one Myr ago), while expansion of its more young phylogenetic group A occurred in late Pleistocene, about 120,000 years ago.

[Different instability of microsatellite CAG repeat in two groups of haplotypes of the human mitochondrial gamma-DNA-polymerase gene].

Polymorphism of two single nucleotide loci rs758130 (T/C) and rs2238296 (T/C) of mitochondrial DNA-polymerase gamma (POLG1) gene has been studied in individuals of different ethnoracial ancestry in Russians and Buryats) with already known genotypes of microsatellite CAG-repeat of this gene. It was found that alleles with the number of repeats unequal to 10 are more often detected on the background of haplotype TT than CC. Results of phylogenetic analysis of the POLG1 gene intron 2 nucleotide sequences in humans and chimpanzee have shown that haplotype TT heterogeneous in relation to CAG-repeat polymorphism appears to be evolutionary younger than haplotype CC. The data obtained can be used for further studies of relationships between CAG-repeat polymorphisms and male infertility.

[Genetic structure of populations of Schrenck newt (Salamandrella schrenckii) based on mitochondrial DNA cytochrome b variability data].

Data on variability of nucleotide sequences of mitochondrial DNA (mtDNA) cytochrome b gene of Schrenck newt, Salamandrella schrenckii (Strauch, 1870), from populations of Primorie and Khabarovsk regions have been received. By means of phylogenetic analysis, two clusters of haplotypes--'southern' cluster 1 and 'northern' cluster 2, with divegence level between them estimated as 3%-- were revealed. Results of analysis of mtDNA and cytochrome b amino acid variation allow us to assume that development of a modern area of Schrenck newt occurred from the south on the north of Primorie region. It was found that 'northern'cluster in contrast to the 'southern' one demonstrates all signs of demographic expansion (i.e., unimodal type of pairwise nucleotide differences, results of tests of selective neutrality of mtDNA variation and good correspondence of genetic parameters to expectations following from the models of demographic expansions).

[Polymorphism of pigmentation genes (OCA2 and ASIP) in some populations of Russia].

In Russian populations, polymorphism of two pigmentation system genes, OCA2 (loci 305, 355, and 419, tested in Russians, Buryats, Chukchi, Koryaks, and Evens) and ASIP (locus 8818, tested in Russians and Buryats) was examined. Pairwise comparisons of the F(ST) distances between the populations showed that only the populations from Northeast Asia (Chukchi, Koryaks, and Evens) were statistically significantly different from all other populations, at least relative to one of the OCA2 locus. In Russians from Pskov oblast and Novgorod oblast, increased frequency (up to 6%) of the OCA2 allele 419A was revealed. In earlier studies, as association of this allele with green eye color was demonstrated. The data obtained in terms of their application for ethnic population genetics.

[Gene pool structure of Russian populations from the European part of Russia inferred from the data on Y chromosome haplogroups distribution].

Population structure of Russian population from the European part of Russia was investigated by analyzing the distribution of 23 SNP makers of Y chromosome in Russian populations from Kaluga oblast, Yaroslavl' oblast, Vladimir oblast, Nizhny Novgorod oblast, Pskov oblast, Tula oblast, Belgorod oblast, and Novgorod oblast. In the populations studied a total of 14 Y-chromosome haplogroups (E, F*, I, J, K*, N3a, N2, P*, R1*, R1a1, C3, H, and A) were discovered, of which haplogroups R1a1, I, and N3a were the prevailing. Analysis of Phi statistics in the populations grouped in accordance to the dialect subdivision of the Russian language, showed the absence of statistically significant differences between Russian population groups. Analysis of the Y-chromosome markers distribution patterns among Russian population (10 population groups) in comparison with the population of Germany (11 population groups) revealed statistically significant differences between the gene pools of Slavs (Russians and Poles) and Teutons (Germans).

[Origin of the Mongoloid component in the mitochondrial gene pool of Slavs].

The data on mitochondrial DNA (mtDNA) restriction polymorphism in Czech population (n = 279) are presented. It was demonstrated that in terms of their structure, mitochondrial gene pools of Czechs and other Slavic populations (Russians, Poles, Slovenians, and Bosnians) were practically indistinguishable. In Czechs, the frequency of eastern-Eurasian (Mongoloid) mtDNA lineages constituted 1.8%. The spread of eastern-Eurasian mtDNA lineages belonging to different ethnolinguistic groups in the populations of Europe was examined. Frequency variations of these DNA lineages in different Slavic groups was observed, with the range from 1.2 and 1.6% in Southern and Western Slavs, respectively, to 1.3 to 5.2% in Eastern Slavs, the Russian population of Eastern Europe. The highest frequency of Mongoloid component was detected in the mitochondrial gene pools of Russian populations from the Russian North and the Northwestern region of Russia. This finding can be explained in terms of assimilation of northern-European Finno--Ugric populations during the formation of the Russian population of these regions. The origin of Mongoloid component in the gene pools of different groups of Slavs is discussed.

Mitochondrial DNA phylogeny in Eastern and Western Slavs.

To resolve the phylogeny of certain mitochondrial DNA (mtDNA) haplogroups in eastern Europe and estimate their evolutionary age, a total of 73 samples representing mitochondrial haplogroups U4, HV*, and R1 were selected for complete mitochondrial genome sequencing from a collection of about 2,000 control region sequences sampled in eastern (Russians, Belorussians, and Ukrainians) and western (Poles, Czechs, and Slovaks) Slavs. On the basis of whole-genome resolution, we fully characterized a number of haplogroups (HV3, HV4, U4a1, U4a2, U4a3, U4b, U4c, U4d, and R1a) that were previously described only partially. Our findings demonstrate that haplogroups HV3, HV4, and U4a1 could be traced back to the pre-Neolithic times ( approximately 12,000-19,000 years before present [YBP]) in eastern Europe. In addition, an ancient connection between the Caucasus/Europe and India has been revealed by analysis of haplogroup R1 diversity, with a split between the Indian and Caucasus/European R1a lineages occurring about 16,500 years ago. Meanwhile, some mtDNA subgroups detected in Slavs (such as U4a2a, U4a2*, HV3a, and R1a1) are definitely younger being dated between 6,400 and 8,200 YBP. However, robust age estimations appear to be problematic due to the high ratios of nonsynonymous to synonymous substitutions found in young mtDNA subclusters.

Mitochondrial DNA variability in Slovaks, with application to the Roma origin.

To gain insight into the mitochondrial gene pool diversity of European populations, we studied mitochondrial DNA (mtDNA) variability in 207 subjects from western and eastern areas of Slovakia. Sequencing of two hypervariable segments, HVS I and HVS II, in combination with screening of coding region haplogroup-specific RFLP-markers, revealed that the majority of Slovak mtDNAs belong to the common West Eurasian mitochondrial haplogroups (HV, J, T, U, N1, W, and X). However, a few sub-Saharan African (L2a) mtDNAs were detected in a population from eastern part of Slovakia. In addition, about 3% of mtDNAs from eastern Slovakia encompass Roma-specific lineages. By means of complete mtDNA sequencing we demonstrate here that the Roma-specific M-lineages observed in gene pools of different Slavonic populations (Slovaks, Poles and Russians), belong to Indian-specific haplogroups M5a1 and M35. Moreover, we show that haplogroup J lineages found in gene pools of the Roma and some Slavonic populations (Czechs and Slovaks) belong to new subhaplogroup J1a, which is defined by coding region mutation at position 8460.

[Variability of fifteen autosomal microsatellite DNA loci in five populations of aboriginal South Siberians].

The allele distributions for 15 STR loci included in the AmpFISTR SGM Plus and AmpFISTR Profiler Plus kits ("Applied Biosystems", USA) were determined in 261 healthy unrelated individuals belonging to five indigenous populations of South Siberia: in Buryats, Altaians, Tofalars, Sojots and Khakassians. No significant differences in allele frequencies were found between populations studied. Combined power of discrimination (PD) for the STR loci investigated were estimated for the populations under study.