Disuniting uniformity: a pied cladistic canvas of mtDNA haplogroup H in Eurasia

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup (Hg) H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian, and Altaian populations. In addition to the seven previously specified subhaplogroups, we define fifteen novel subclades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one subcluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1*, H1b, H1f, H2a, H3, H6a, H6b, and H8 demonstrate distinct phylogeographic patterns. The monophyletic subhaplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.     

Origin and diffusion of mtDNA haplogroup X

A maximum parsimony tree of 21 complete mitochondrial DNA (mtDNA) sequences belonging to haplogroup X and the survey of the haplogroup-associated polymorphisms in 13,589 mtDNAs from Eurasia and Africa revealed that haplogroup X is subdivided into two major branches, here defined as “X1” and “X2.” The first is restricted to the populations of North and East Africa and the Near East, whereas X2 encompasses all X mtDNAs from Europe, western and Central Asia, Siberia, and the great majority of the Near East, as well as some North African samples. Subhaplogroup X1 diversity indicates an early coalescence time, whereas X2 has apparently undergone a more recent population expansion in Eurasia, most likely around or after the last glacial maximum. It is notable that X2 includes the two complete Native American X sequences that constitute the distinctive X2a clade, a clade that lacks close relatives in the entire Old World, including Siberia. The position of X2a in the phylogenetic tree suggests an early split from the other X2 clades, likely at the very beginning of their expansion and spread from the Near East.     

Distribution of the HIV-1 resistance-conferring alleles (CCR5delta32, CCR2-64I, and SDF1 3'A) in Russian, Ukrainian, and Belarusian populations

The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1 3'A, known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians, respectively. The proportion of the individuals without any of three protective alleles among Russians, Ukrainians, and Belarussians constituted 49, 65, and 61%, respectively. The genotype frequencies for the three loci studied were in Hardy-Weinberg equilibrium. Based on the three-locus genotype frequencies, the hazard ratios (relative hazards, RH) of AIDS onset in HIV-infected individuals in each sample were calculated as ranging from 0.79 to 0.88. In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS-protective alleles tested, as well as the frequencies of the corresponding genotypes and the relative hazards of AIDS onset were within the range of these parameters for the other European populations. The data on the allele frequencies and the relative hazard values in Russians, Ukrainians and Belarussians can be used as the predictors of AIDS onset and progression rate in HIV-1-infected individuals from the populations studied.     

A molecular characterization of the charismatic Faroe house mouse

Faroe house mice are a ‘classic’ system of rapid and dramatic morphological divergence highlighted by J. S. Huxley during the development of the Modern Synthesis. In the present study, we characterize these charismatic mice using modern molecular techniques, examining specimens from all Faroe islands occupied by mice. The aims were to classify the mice within the modern house mouse taxonomy (i.e. as either Mus musculus domesticus or Mus musculus musculus) using four molecular markers and a morphological feature, and to examine the genetic diversity and possible routes of colonization using mitochondrial (mt) control region DNA sequences and microsatellite data (15 loci). Mice on the most remote islands were characterized as M. m. domesticus and exhibited exceptionally low genetic diversity, whereas those on better connected islands were more genetically diverse and had both M. m. musculus and M. m. domesticus genetic elements, including one population which was morphologically M. m. musculus‐like. The mtDNA data indicate that the majority of the mice had their origins in south‐western Norway (or possibly southern Denmark/northern Germany), and probably arrived with the Vikings, earlier than suggested by Huxley. The M. m. musculus genetic component appears to derive from recent mouse immigration from Denmark. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 471–482.     

Distribution of the HIV-1 Resistance-Conferring Alleles (CCR5delta32, CCR2-64I, and SDF1-3′A) in Russian, Ukrainian, and Belarusian Populations

The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1-3A, known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians, respectively. The proportion of the individuals without any of three protective alleles among Russians, Ukrainians, and Belarussians constituted 49, 65, and 61%, respectively. The genotype frequencies for the three loci studied were in Hardy–Weinberg equilibrium. Based on the three-locus genotype frequencies, the relative hazards of AIDS onset in HIV-infected individuals in each population were calculated as ranging from 0.79 to 0.88. In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS-protective alleles tested, as well as the frequencies of the corresponding genotypes and the relative hazards of AIDS onset were within the range of these parameters for the other European populations. The data on the allele frequencies and the relative hazard values in Russians, Ukrainians, and Belarussians can be used as the predictors of AIDS onset and progression rate in HIV-1-infected individuals from the populations studied.     

Identification of structural DNA variations in human cell cultures after long-term passage

Random amplified polymorphic DNA (RAPD) analysis was adapted for genomic identification of cell cultures and evaluation of DNA stability in cells of different origin at different culture passages. DNA stability was observed in cultures after no more than 5 passages. Adipose-derived stromal cells demonstrated increased DNA instability. RAPD fragments from different cell lines after different number of passages were cloned and sequenced. The chromosomal localization of these fragments was identified and single-nucleotide variations in RAPD fragments isolated from cell lines after 8–12 passages were revealed. Some of them had permanent localization, while most variations demonstrated random distribution and can be considered as de novo mutations.     

Analysis of the DRD4 Gene Polymorphism in Populations of Russia and Neighboring Countries

Allele and genotype frequencies of the VNTR polymorphism in the third exon of humanDRD4 gene were determined in 544 individuals living in Russia (Russians, Bashkirs, Tatars, and Mordovians) and in the neighboring countries (Kazakhs and Ukrainians). The data obtained were compared with the allele frequency distribution patterns reported for the populations of Eurasia. Similarly to other Eurasian populations, in our population samples R4 allele was prevalent (64 to 87%). The frequency of this allele in the populations of Western Europe constitute 61 to 71%, while in the populations of Asia it varies from 74 to 96%. In this respect, the populations studied occupied the intermediate position. In the samples examined the R7 allele frequency decreased from 7% in Ukrainians to 1% in Bashkirs, while in Kazakhs and Mordovians the allele was absent. This finding was consistent with theR7 allele distribution pattern in the populations of Eurasia, characterized by higher frequency in the West and lower frequency or absence of the allele in the East. In the group of 22 Eurasian populations, the R7 allele frequency negatively correlated with the frequency of the R4 allele (r = -0.86 at P < 0.001). Unlike the R4 and R7 alleles, the frequency of which changed in the eastward direction, the R2 allele frequency distribution displayed slightly expressed latitudinal increase southwards. The DRD4 genotype distribution deviated from the equilibrium in most of the samples examined. In some samples, statistically significant increase of the R2/R2homozygotes frequency was demonstrated. One of the possible explanations of this phenomenon is assortative mating with respect to phenotypic (behavioral) allele manifestation. The data obtained can serve as the basis for the investigation of the possible role of the DRD4 alleles as the risk factors for the development of alcoholism and other types of addictions.     

Fatal manifestation of a de novo ND5 mutation: Insights into the pathogenetic mechanisms of mtDNA ND5 gene defects

We report the de novo occurrence of a heteroplasmic 12706T-->C (12705C) ND5 mutation associated with the clinical expression of fatal Leigh syndrome. Phylogenetic analysis of several cases having the 12706C mutation confirmed that this mutation occurred independently in distinctive mtDNA backgrounds. In each of these cases, the low level of heteroplasmy and the association of the mutation with a deleterious phenotype indicated that the 12706C had a primary role in the expression of LS/MELAS in its carriers. Secondary structure analysis of the ND5 protein further supported the deleterious role of the 12706C mutation, as it was found to affect a functionally significant transmembrane domain that is likely responsible for the proton-translocation function of complex I.     

The Distribution of Some Hydrolytic Enzymes in the Wheat Seed

A histochemical study of dry and germinated wheat embryos andseeds has been made to identify the sites of activity of 3'-and 5'-nucleotidases, phosphatases, lipase, and esterase. Theenzymes all showed the same distribution, with the coleorhizaas the most prominent site of activity in the dry embryo, especiallywhen compared with the adjacent roots with very low activity.Investigations of the whole seed after 24 h germination showeda very high activity in the aleurone cells and high activitiesin the scutellum and coleorhiza. The epithelium and provasculartissues of the scutellum showed moderate to low activity whilethe endosperm had little or none. Hydrolase activity also wasfound in the testa. The function of the coleorhiza. as firstfood reserve for the roots and its location at the most importantsite of water entry, is discussed.