[Gene pool of ethnic groups of the caucasus: results of integrated study of the Y chromosome and mitochondrial DNA and genome-wide data].

Genetic diversity has been analyzed in 22 ethnic groups of the Caucasus on the basis of data on Y-chromosome and mitochondrial DNA (mtDNA) markers, as well as genome-wide data on autosomal single-nucleotide polymorphisms (SNPs). It has been found that the West Asian component is prevailing in all ethnic groups studied except for Nogays. This Near Eastern ancestral component has proved to be characteristic of Caucasian populations and almost entirely absent in their northern neighbors inhabiting the Eastern European Plain. Turkic-speaking populations, except Nogays, did not exhibit an increased proportion of Eastern Eurasian mtDNA or Y-chromosome haplogroups compared to some Abkhaz-Adyghe populations (Adygs and Kabardians). Genome-wide SNP analysis has also shown substantial differences of Nogays from all other Caucasian populations studied. However, the characteristic difference of Nogays from other populations of the Caucasus seems somewhat ambiguous in terms of the R1a1a-M17(M198) and R1b1b1-M73 haplogroups of the Y chromosome. The state of these haplogroups in Turkic-speaking populations of the Caucasus requires further study.

[Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

[Phylogenetic analysis of ancient mitochondrial DNA lineages of human remains found in Yakutia].

Molecular genetic analysis of ancient human remains are mostly based on mitochondrial DNA due to its better preservation in human skeletons in comparison with nuclear DNA. We investigated mtDNA extracted from human skeletons found in graves in Yakutia to determine their haplotypes and to compare them with lineages of modern populations. Ancient DNA was extracted from fragments of three skeletons of Yakut graves at At-Dabaan, Ojuluun and Jaraama sites (dating XVIII century) and two skeletons of Neolithic graves at Kerdugen site found in central Yakutia (Churapchinsky, Kangalassky and Megino-Kangalassky districts of Yakutia). Five different haplotypes belonging to specific Asian haplogroups were identified. Lineages of mtDNA of Yakut graves belong to haplo-groups C4a, D5a2 and B5b. Our results indicate the continuity of mitochondrial lineages in the Yakut gene pool during the last 300 years. Haplotypes of two humans from Kerdugen site graves belong to haplogroups A4 and G2a/D. We compared these haplotypes with that of 40,000 Eurasian individuals, 900 of them from Yakutia. No exact matches were found in Paleoasian populations of Chukchi, Eskimos, Koryaks and Itelmen. Phylogenetically close haplotypes (+/- 1 mutation) were found in populations of Yakuts and Evenks, as well as in some populations of China, Southern and Western Siberia.

Deep common ancestry of indian and western-Eurasian mitochondrial DNA lineages.

About a fifth of the human gene pool belongs largely either to Indo-European or Dravidic speaking people inhabiting the Indian peninsula. The 'Caucasoid share' in their gene pool is thought to be related predominantly to the Indo-European speakers. A commonly held hypothesis, albeit not the only one, suggests a massive Indo-Aryan invasion to India some 4,000 years ago [1]. Recent limited analysis of maternally inherited mitochondrial DNA (mtDNA) of Indian populations has been interpreted as supporting this concept [2] [3]. Here, this interpretation is questioned. We found an extensive deep late Pleistocene genetic link between contemporary Europeans and Indians, provided by the mtDNA haplogroup U, which encompasses roughly a fifth of mtDNA lineages of both populations. Our estimate for this split is close to the suggested time for the peopling of Asia and the first expansion of anatomically modern humans in Eurasia [4] [5] [6] [7] [8] and likely pre-dates their spread to Europe. Only a small fraction of the 'Caucasoid-specific' mtDNA lineages found in Indian populations can be ascribed to a relatively recent admixture.

[The effect of marriage migration on the genetic structure of the Taimyr Nganasan population: genealogical analysis inferred from MtDNA markers].

The marriage structure of Nganasans during the time period from 1796 to 1991 and genealogy of carriers of mitochondrial DNA haplotypes was studied in a sample of 280 individuals. It was shown that, from the beginning of its formation to the late 1970s, the population exhibited high endogamy (1976, 83.8%; 1926, 88.4%; 1976, 74.3%). The main source of traditional marriage migration (preferentially female) was populations of Entsy and, indirectly, Nentsy. Intense assimilation of Nganasans by the immigrant population, and to a lesser extent, by Dolgans, in the second half of the 20th century resulted in a reduction of endogamy index in Avam Nganasans to 42.5% by 1991. Assimilation by the immigrants was predominantly paternal, promoting preservation of the historically formed genetic diversity of the Nganasan mitochondrial gene pool. Genealogical analysis of mtDNA haplotypes showed that a relatively high total frequency of Western Eurasian mtDNA haplogroups (20.4%) in the Mongoloid (according to anthropological type) Nganasan population is explained not only by the common ethnic origin with Entsy and Nentsy, but also by direct marriage migration from the Entsy population and indirect marriage migration, from the Nentsy population. This migration led to accumulation of Entsy-Nentsy maternal lineages in the genealogy of Avam Nganasans (38.9% of the total number). Of all mtDNA haplotypes, 28.6% were introduced to Avam Nganasans by female Entsy and Nentsy, whereas the total frequency of these haplotypes was 0.204. Genetic diversity of mitochondrial DNA haplotypes was 0.935.

[Analysis of mitochondrial DNA variation in the population of Oroks].

Mitochondrial DNA (mtDNA) variation was studied in population of Oroks (n = 61), the indigenous inhabitants of Eastern Siberia. Most of the mtDNA types examined fell into five haplogroups (C, D, G, M10, and Y) typical of Eastern Eurasian populations. For three haplogroups (D, C, and M10), the founder effect was established. In one individual, a unique lineage belonging to haplogroup HV and typical of Caucasoids was detected.

The evidence of mtDNA haplogroup F in a European population and its ethnohistoric implications.

Mitochondrial DNA polymorphism was analysed in a sample of 108 Croatians from the Adriatic Island isolate of Hvar. Besides typically European varieties of human maternal lineages, haplogroup F was found in a considerable frequency (8.3%). This haplogroup is most frequent in southeast Asia but has not been reported before in Europe. The genealogical analysis of haplogroup F cases from Hvar suggested founder effect. Subsequent field work was undertaken to sample and analyse 336 persons from three neighbouring islands (Brac, Korcula and Krk) and 379 more persons from all Croatian mainland counties and to determine if haplogroup F is present in the general population. Only one more case was found in one of the mainland cities, with no known ancestors from Hvar Island. The first published phylogenetic analysis of haplogroup F worldwide is presented, applying the median network method, suggesting several scenarios how this maternal lineage may have been added to the Croatian mtDNA pool.

Structure of the human genomic region homologous to the bovine prochymosin-encoding gene.

Two human genomic libraries were probed with bovine prochymosin (bPC) cDNA. Recombinant clones covering a genomic region homologous to the entire coding region and flanking sequences of the bPC gene were isolated. Human sequences homologous to exons of the bPC gene are distributed in a DNA fragment of 10 kb. Alignment of the human sequences and the exons of bPC reveals that the human 'exons' 1-3, 5 and 7-9 have sizes identical to the corresponding bovine exons, but a nucleotide (nt) has been deleted in the human exon 4 and two nt in the human exon 6. The aligned human sequence and the coding part of bPC gene share 82% nt homology, the value ranging, in separate exons, from 76 (exon 1) to 84% (exons 5 and 6). 150 bp of 5'-flanking sequence of the human gene has 75% homology to the corresponding region of bPC gene and contains a TATA-box in a similar position. A 1-nt deletion in the human exon 4 would shift the translational reading frame of a putative human PC mRNA relative to bPC mRNA, and result in an in-phase terminator spanning codons 163 and 164 in bPC mRNA. Another terminator in-phase with the amino-acid sequence encoded by the bPC gene occurs in the human exon 5 and the second frameshift mutation in exon 6. Thus, the nt sequence analysis of the human genomic region has revealed the presence of mutations that have rendered it unable to produce a full-length protein homologous to bPC and, therefore, we refer to this gene as a human prochymosin pseudogene (hPC psi). Blot-hybridization analysis of human genomic DNA indicates that hPC psi is a single gene in the human genome.

Ribosomal protein L16 binds to the 3'-end of transfer RNA.

Escherichia coli 50 S ribosomal subunits were reconstituted with and without protein L16 present. The latter particles, although active in puromycin reaction, were unable to use CACCA-Phe as an acceptor substrate. We also found that L16 interacts directly with this oligonucleotide and, in the complex with tRNA, protects its 3'-end from pancreatic ribonuclease digestion. We suggest that the role of L16 is in the fixation of the aminoacyl stem of tRNA to the ribosome at its A-site.

5 S RNA-protein complex is involved in ribosomal subunit association.

The immobilized tRNA-50 S ribosomal subunit protein (TP50) complex binds the smaller ribosomal subunit. We constructed tRNA . TP50 . 5 S [32P] RNA and tRNA . TP50 . t [32P] RNA complexes and investigated the accessibility of the 32P-labelled tRNAs to ribonuclease T1. It was found that in this complex both 5 S RNA and tRNA are attacked by T1 RNase. In sharp contrast, the addition of 30 S subunit protects 5 S RNA as well as tRNA from degradation. We suggest that 5 S RNA-TP50 complex is exposed to the ribosomal interface and is involved in subunit interaction.

The interaction of ribosomal protein L16 and its fragments with tRNA.

Two large proteolytic fragments of Escherichia coli 50 S ribosomal subunit protein L16 were generated by limited hydrolysis with chymotrypsin (missing 9 N-terminal amino acids) and trypsin (missing 16 N-terminal amino acids). It was found that while intact L16 and its chymotryptic fragment both interact with tRNA (Kd = 5.4 x 10(-7) M), the tryptic fragment does not. These results are interpreted in terms of possible significance of the residues 10-16 in the peptidyl transferase activity.

The properties of the complex between ribosomal protein L2 and tRNA.

Escherichia coli ribosomal protein L2 interacts with fMet-tRNAfMet and NacPhe-tRNAPhe in solution, protecting their 3'-ends from enzymatic degradation. At the same time L2 enhances the rate of spontaneous hydrolysis of the ester bonds between terminal riboses and amino acyl moieties of these two peptidyl-tRNA analogues. L2 has, however, only a slight effect on the rate of spontaneous deacylation of aminoacyl-tRNAs. We suggest that the role of L2 is in the fixation of the aminoacyl stem of tRNA to the ribosome at its P-site, and speculate that this protein is directly involved in the peptidyl transferase (PT) reaction.

Human Y-chromosome variation in the western Mediterranean area: implications for the peopling of the region.

Y-chromosome variation was analyzed in a sample of 1127 males from the Western Mediterranean area by surveying 16 biallelic and 4 multiallelic sites. Some populations from Northeastern Europe and the Middle East were also studied for comparison. All Y-chromosome haplotypes were included in a parsimonious genealogic tree consisting of 17 haplogroups, several of which displayed distinct geographic specificities. One of the haplogroups, HG9.2, has some features that are compatible with a spread into Europe from the Near East during the Neolithic period. However, the current distribution of this haplogroup would suggest that the Neolithic gene pool had a major impact in the eastern and central part of the Mediterranean basin, but very limited consequences in Iberia and Northwestern Europe. Two other haplogroups, HG25.2 and HG2.2, were found to have much more restricted geographic distributions. The first most likely originated in the Berbers within the last few thousand years, and allows the detection of gene flow to Iberia and Southern Europe. The latter haplogroup is common only in Sardinia, which confirms the genetic peculiarity and isolation of the Sardinians. Overall, this study demonstrates that the dissection of Y-chromosome variation into haplogroups with a more restricted geographic distribution can reveal important differences even between populations that live at short distances, and provides new clues to their past interactions.

[Diversity of mitochondrial DNA haplotypes in ethnic populations of the Volga-Ural region of Russia]. / Raznoobrazie gaplogrupp mitokhondrial'noi DNK u narodov Volgo-Ural'skogo regiona Rossii.

The mtDNA polymorphism was analyzed in eight ethnic groups (N = 979) of the Volga-Ural region. Most mtDNA variants belonged to haplogroups H, U, T, J, W, I, R, and N1 characteristic of West Eurasian populations. The most frequent were haplogroups H (12-42%) and U (18-44%). East Eurasian mtDNA types (A, B, Y, F, M, N9) were also observed. Genetic diversity was higher in Turkic than in Finno-Ugric populations. The frequency of mtDNA types characteristic of Siberian and Central Asian populations substantially increased in the ethnic groups living closer to the Urals, a boundary between Europe and Asia. Geographic distances, rather than linguistic barriers, were assumed to play the major role in distribution of mtDNA types in the Volga-Ural region. Thus, as concerns the maternal lineage, the Finno-Ugric populations of the region proved to be more similar to their Turkic neighbors rather than to linguistically related Balto-Finnish ethnic groups.

[Stimulation of peptidyltransferase activity of 50S subunits by alcohols]. / Stimuliatsiia peptidiltransferaznoi aktivnosti 50S subchastitsy spirtami.

We have demonstrated that in certain conditions 50S subunits can transfer peptide moiety from peptidyl-tRNA to puromycin in the absence of alcohol. Monovalent cations NH4+ and K+ support this reaction, while Na+ and Li+ are ineffective. Optimal concentration for NH4+ is 1.8 M. Mg2+ ion concentrations above 12 mM are needed as well as an elevated temperature (30 degrees C). Using the alcohol-free puromycin reaction of 50S subunits we show that alcohol activates the peptidyl transferase center, but does not participate in the puromycin reaction. Neither does it change the protein composition of subunits.

[Protein L16 of the Escherichia coli ribosome: possible role in protein biosynthesis]. / Belok L16 ribosomy Escherichia coli: vozmozhnaia rol' v biosinteze belka.

We show that Escherichia coli 50S ribosomal subunits depleted of protein L16 can nevertheless catalyze the transfer of the peptide moiety from fMet-tRNA to puromycin, being, however, unable to use a fragment CACCA-Phe as an acceptor substrate. On the other hand, we found that protein L16 as well as its large fragment (amino acids 10-136) both interact with tRNA in solution (Kd approximately 10(-7) M). Moreover, L16 interacts with CACCA-Phe in solution as well as protects 3' end of tRNA from the enzymatic degradation. We suggest that L16, although not being the peptidyl transferase as such, is involved in the binding of the 3' end cytidines of tRNA into the ribosomal A site.

[Conformational isomers of rat liver 5S ribosomal RNA]. / Konformatsionnye izomery 5S RNK ribosom pecheni krysy.

The rat liver 5S RNA when denaturated by urea or EDTA, or even without any special treatment, undergoes conformational changes leading to the formation of three electrophoretically distinct isomeres of the molecules with relative mobilities 0.39, 0.44 and 0.47. The band with the slowest mobility corresponds apparently to the native 5S RNA since it is specific for both freshy isolated and renaturated 5S RNA. Moreover, it was found that denaturation of the immobilized 5 S RNA decreases significantly its ability to form a complex with the rat liver 60S ribosomal subunit proteins L6, L7, L8, L18 and L35.

[Analysis of mitochondrial DNA haplotypes in yakut population]. / Analiz linii mitokhondrial'noi DNK v populiatsii iakutov.

To study the mitochondrial gene pool structure in Yakuts, polymorphism of mtDNA hypervariable segment I (16,024-16,390) was analyzed in 191 people sampled from the indigenous population of the Sakha Republic. In total, 67 haplotypes of 14 haplogroups were detected. Most (91.6%) haplotypes belonged to haplogroups A, B, C, D, F, G, M*, and Y, which are specific for East Eurasian ethnic groups; 8.4% haplotypes represented Caucasian haplogroups H, HV1, J, T, U, and W. A high frequency of mtDNA types belonging to Asian supercluster M was peculiar for Yakuts: mtDNA types belonging to haplogroup C, D, or G and undifferentiated mtDNA types of haplogroup M (M*) accounted for 81% of all haplotypes. The highest diversity was observed for haplogroups C and D, which comprised respectively 22 (44%) and 18 (30%) haplotypes. Yakuts showed the lowest genetic diversity (H = 0.964) among all Turkic ethnic groups. Phylogenetic analysis testified to a common genetic substrate of Yakuts, Mongols, and Central Asian (Kazakh, Kyrgyz, Uigur) populations. Yakuts proved to share 21 (55.5%) mtDNA haplogroups with the Central Asian ethnic groups and Mongols. Comparisons with modern paleo-Asian populations (Chukcha, Itelmen, Koryaks) revealed three (8.9%) haplotypes common for Yakuts and Koryaks. The results of mtDNA analysis disagree with the hypothesis of an appreciable paleo-Asian contribution to the modern Yakut gene pool.