Biomedical subjects
Publications and source records attributed to Iu G Rychkov.
Evidence for alterations in chromosomes of experimental animals (rats) and humans after gunshot wounds is presented. The rate of chromatid exchanges induced by gunshot wounds in humans depend on the saturation of body tissues with ascorbic acid. It is assumed that free-radical processes underlie the deleterious effect of gunshot wounds on chromosomes.
A map of gene migration rate m in the indigenous population of Siberia and the Russian Far East was constructed on the basis of data obtained from questionnaires of 1960 to 1990. The mean gene migration rate weighted with respect to the region area and averaged over 3951 grid nodes was m = 0.0083. Weighting with respect to population density yielded a significantly lower rate (m = 0.0053), which reflected a more intense gene exchange in less populous regions of traditional nomadism. The association between gene migration rate m and genetically effective population size Ne was analyzed. The parameter Nem, which characterizes the interpopulation gene diversity, was used to identify regions where this parameter is autoregulated and those where the autoregulatory mechanisms were disrupted. A tree of ethnolinguistic types was constructed. Its analysis did not reveal any association between migration structure and linguistic characteristics, suggesting that the spreading of cultural elements is not necessarily associated with migration. The tree was also used to construct a map of ethnos-forming migration; its major element reflected migration from the Baikal and Altai regions to the ethnic region of modern Yakuts.
A factor of the association between gene geographical data and populations of the mapped region was analyzed. This allowed for correction of the equations for the major statistical parameters of gene geographical maps (mean, variance, etc.) and gene geographical methods of estimating the spatial nonstationarity of data within a mapped region. The proposed approach is based on the use of the population density in a mapped region as a factor reflecting the anisotropy of the geographical space. The population density of the North Eurasian indigenous populations was mapped, and the application of the resulting map was illustrated with an example.
The problem of the relationship between the state of the gene pool and population health was formulated. The subdivision into latitudinal zones, which is a characteristic feature of the northern Eurasian gene pool, was studied. This subdivision was expressed in the geographical distribution of the second principal component (PC2.G) of the total variance of 100 allelic frequencies for 34 polymorphic loci. It was suggested that this distribution of PC2.G resulted from the genetic adaptation of the population to the latitudinal zonality that is characteristic of northern Eurasia. It was also suggested that the latitudinal geographic variation was not inherent in the northern Eurasian gene pool and was younger than its total historical age. The evolutionary age of the principal components of the gene pool was estimated based on the geography of the principal components of the geographic variability of the late Paleolithic material culture, as well as the paleogeography of the Quaternary period. It was demonstrated that the first principal component of the modern gene pool was almost completely formed in the late Pleistocene; hence, its age is at least 16,000-26,000 years. The age of the second principal component (PC2.G) was estimated at less than 12,000-15,000 years; it was mostly formed in Holocene. A hypothesis was advanced that genetic adaptation occurs at the cost of population health, with the cost increasing as the evolutionary age of the genetic adaptation decreases. It was suggested that the latitudinal zonality of gene pool was accompanied by a similar zonality in the geography of morbidity as a cost of genetic adaptation.
New data on the association of the state of health and the disease incidence with the gene pool were obtained in the East European population. The second principal component (PC2.G, 11.4% of the total variance) of the geographic variation in the gene pool (100 alleles of 34 loci) showed a distinct latitudinal dependence corresponding to the natural zonality of Eastern Europe. This was also characteristic of the first principal component (PC1.M, 75.6% of the total variance) of the geographic variation in the disease incidence (i.e., the number of all new cases diagnosed in out-patient clinics per year) in the rural population. The disease incidence decreased from the south-southeast to the north-northwest in European Russia. The coefficient of the geographic pairwise correlation between PC2.G and PC1.M was r = 0.945; their specific correlation remained high (r = 0.864), even after a correction for the effects of age composition and heterozygosity. Thus, an insignificant variation in the gene pool was shown to significantly affect the geographic distribution of disease incidence in the East European population of Russia (eta 2 = 0.892). A correlation of mapped geographic distributions of PC1.M and PC2.G in the modern population with those of the principal components of the geographic variation of the late Paleolithic material culture in Eastern Europe was analyzed. The origin of the latitudinal zonality of the modern gene pool was dated back to the late Pleistocene-early Holocene. A conclusion was made that diseases that affected reproduction and lethality in the Paleolithic population still represent a mechanism of the gene pool's adaptation to the natural zonality of the environment. The latitudinal zonality of disease incidence, which was characteristic of the ancient population, is conserved in the today's population, owing to the gene pool.
Nineteen mtDNA samples from osseous remains found in the Ust-Ida I burial ground (middle Angara River) were analyzed. An ancient population dated back to 4020-3210 B.C. by radiocarbon (14C) analysis and archeologically assigned to the Neolithic Isakovo culture of the Baikal region was described in terms of molecular genetics. Data on restriction-site polymorphisms in fragment 16,106-16,545 of the mtDNA D-loop were obtained for seven restriction endonucleases. On the basis of these data, the mitotypic structure and nucleotide diversity of the ancient population were determined. The molecular genetic characteristics of the Neolithic population were compared to the modern populations of Siberia, Mongolia, and Urals. The data obtained indicate that the studied Baikal Neolithic population was ancestral for the modern indigenous Siberian population. The time of divergence of the three regional populations (5572 years ago) was estimated from the genetic distances between the Neolithic and modern Siberian populations, assuming that the average rate of nucleotide substitution was constant. This estimation agrees with the results of the radiocarbon dating (5542-5652 years ago). The fact that the studied samples were 14C-dated allowed the rate of nucleotide substitution in the studied region of mtDNA D-loop to be directly determined.
A method of transformation of census data on population migration into data on gene migrations is proposed. Based on the 1970 Population census of the former Soviet Union, coefficients of effective direct migration m in 91 population of the oblast size in the European part of Russia were estimated. Each coefficient was calculated as the geometric mean of effective values for the island and stepping-stone models of population structure. A map of the geographic distribution of gene migrations was constructed. Low rates of gene migrations were shown to be associated with steppe-forest and deciduous forest zones. Mean coefficients of gene migration estimated from the observed data for the European region and from the map data weighted by the area sizes were respectively m = 0.0156 +/- 0.0011 and m = 0.0232 +/- 0.0011. In view of the fact that the census data were collected simultaneously, all m values were multiplied by 2.8 in order to estimate gene migration rate per generation. Correlation analysis of gene migration coefficients m and genetically effective population sizes Ne demonstrated that these population parameters are independent. This analysis showed the reverse relationship between the rate of gene migration into a population and population density, in particular, density of settlements within the population area.
On the basis of 655 direct and indirect estimations of effective size (Ne) of rural populations, a map of the geographic distribution of Ne in northern Eurasia was constructed. A geographic cline of Ne was found, with its value decreasing by three orders of magnitude from the direction of southwest (the western Caucasus and Central Asia) to northeast (the coasts of the Sea of Okhotsk and the Bering Sea). The area of highest distribution density of mean Ne values was situated meridionally between the Ob and Yenisei rivers from the Arctic coast of Taimyr Peninsula to the eastern Sayany and the south Baikal regions. Another similar area covered the south Baltic region, Belarus, and northwestern Ukraine. The average effective population size in northern Eurasia was Ne = 211.6, the geometrical mean G = 176, the harmonic mean H = 147, and the modal value Mo = 102. These characteristics of effective population size indicate a considerable contribution of stochastic gene drift to the differentiation of the northern Eurasian gene pool and the geographic cline of the rate of gene drift in the subcontinent. By means of transformation of the Ne map, a map for the rate of stochastic gene drift (1/4Ne) in northern Eurasia was obtained.
Results of long-term studies of Russian authors on regularities of expression of hereditary biochemical diversity in evolution and development are reviewed. Primary attention is given to the concepts of genetic monomorphism and genetic stability of population systems, principles of adaptive gene pool structure and optimum genetic diversity, historical and conservation genetics, the concept of the multilevel gene expression, and temporal regulation of ontogenetic functioning of gene clusters coding for enzymes. A universal genetic approach to the problems of evolution and ontogeny is proposed. A population is regarded as a superorganism whose key property is the hierarchic structure of its genetic stability from the stability of monomorphic genes via stability of polymorphic gene frequencies in a multilevel population system to the stability of the total amount of gene diversity in this system. A multicellular organism is also regarded as a developing hierarchical system of populations of cells and genes interacting in a nonrandom fashion. This maintains stability of metabolic processes and is expressed in consistent correlations between monogenic and polygenic morphophysiological characters. Properties of both organisms are determined by the adaptive heterozygosity optimum, the disturbance of which has negative consequences for both individuals and populations. On the basis of these results and the concept on the common nature of evolutionary and ontogenetic processes, the following conclusions are drawn: genetic processes can be either favorable or adverse for developing organisms and populations; the state of genetic processes can be determined by analysis of gene diversity and their deviations from the optimum, taking into account the adaptive gene pool structure; and negative hazardous consequences of extreme external effects at both the individual and population levels can be detected by methods of biochemical genetics in specially planned monitoring programs. Knowledge of normal processes of realization of hereditary information in evolution of populations and in ontogeny opens up new perspectives in detection of unfavorable processes and their correction. This approach proved promising both for preventive and clinical medicine and for exploitation and artificial reproduction of biological resources.
A significant geographical correlation (r = 0.719) was found between the logarithm of effective size (InNe) and heterozygosity level (H) in populations under the assumption of the Hardy-Weinberg equilibrium. The area of highest positive correlation was positioned meridionally between the Ob and Yenisei rivers, from the Arctic coast of Taimyr Peninsula to eastern Sayans and the southern Cis-Baikal region, i.e., in the same region where the highest distribution density of mean Ne values was found. Two additional areas of high correlations were found on the northern Black Sea coast and in the lower Lena river region. Analysis and mapping of correlation ratios eta H/lnNe2 and eta lnNe/H2 revealed that effective size substantially influenced heterozygosity level (as could be expected in the case of an intense gene drift), and heterozygosity level influenced effective size to the same extent. The latter relationship indicated an intense adaptation, and changes in diversity of the gene pool caused substantial demographic changes. However, this might be accounted for by direct gene migration into a population prevailing over reverse migration, i.e., mechanical population growth prevailing over natural growth.
The genetic patterns of 25 populations from seven ethnic groups living in the Ural region (Komi, Komi-Permyaks, Udmurts, Mansi, Nentsy, Tatars, and Chuvashes) were studied. Immunological, biochemical, and physiological markers of the loci ABO, FUT, RH, P, FY, DI, KEL, LU, LE, JK, HP, GC, C'3, TF, PI, ACP1, GLO1, ESD, PGD, PGM1, PTC, and CB were studied. The average ethnic frequencies of the alleles and haplotypes studied were estimated. It was demonstrated that the Ural populations living to the west of the Urals, although of different origin, were more similar genetically than populations of common (Ural) origin living on different sides of the Urals, with respect to the majority of the traits studied.
New data about eleven polymorphic sites of restriction in the D-loop of mtDNA revealed with the Ava II, BamH I, EcoR V, Hae III, Kpn I, Rsa I, and Sau3A I restriction enzymes in native populations of the Caucasus (N = 40) and Siberia (N = 44) are presented. A comparison of these groups with each other and with common data for western and eastern Europe as well as for central and eastern Asia reveals a large similarity of all the population groups of Eurasia in respect to the frequency of each polymorphic site separately. The interpopulation differentiation of frequency of polymorphic restriction sites in Eurasia is low and identical at such different hierarchical levels of population structure as ethnic group and extended regional population group. An analysis of differences between sites in the frequency of the presence of restriction sites for BamH I, EcoR V, Hae III, and Sau3A I and the absence of sites for Ava II, Kpn I, and Rsa I at definite loci of the nucleotide chain allowed determination of the region of equilibrium between direct, site-generating, and reverse mutations to be 0.43q. Among eleven polymorphic restriction sites analyzed here, only polymorphism in the Hae III site at the position 16,517 in the population of Eurasia was characterized with frequencies close to equilibrium that determined the extremely large evolutionary age of this polymorphism.
Transformations of computer maps of geographical distribution of gene frequencies using basic mathematical statistical procedures are considered. These transformations are designated as statistical transformation of maps. Two transformation groups are considered: of one map separately and of a group of maps. Transformations possess a value beyond their use as intermediate stages of more complicated cartographical analysis: the resulting maps carry entirely new information on the geography of genes or a gene pool. This article considers three examples of obtaining new genetic profiles using statistical transformation algorithms. These profiles are of: heterozygosity (of HLA-A, B, C loci in northeastern Eurasia); (2) disease risk (Rh-incompatibility of mother and child with simultaneous registration of Rh and ABO blood groups in Eastern Europe); (3) genetic distances (from own mean ethnic values for Belarus' and from mean Russian values for the gene pool of Eastern Europe).
General statistical information that can be derived from an electronic map and listed in its legend is reviewed. Certain map information (extrema, mean and variance of mapped values, the number of initial and mapped values, their statistical distributions) can be used in analysis not only of gene pool, but also of phene pool maps. Another portion of map information, on total gene diversity, heterozygosity, and interpopulation differentiation, is important for consequent detailed analysis of a gene pool. Statistical information that is derived from a genogeographic map aids understanding of the content of a map and is used in comparative quantitative analysis of different regions and various mapped parameters. The possibilities for interpretation of statistical information of genogeographic maps are shown using the human gene pool as an example. Maps of frequencies of ABO-O and Rh-d blood group genes in three hierarchically subordinate gene pools of native inhabitants of Belarus, the Black Sea-Baltic region, and northeast Eurasia are presented for this purpose.
A method for DNA extraction from fossil bones based on DNA water elution from the bone powder is proposed. The method allows extraction of paleo-DNA from the great number of bone specimens simultaneously within one day and in quantities sufficient for DNA amplification by the polymerase chain reaction.
Deletion-insertion polymorphism in the V-region of mitochondrial DNA was analysed in ten mongoloid populations of Siberia. Frequencies of 9-bp deletion and 4-bp insertion in the populations were: 7.7 and 1.5% in Buryats; 10.2 and 0.8% in north Altais: 1.4 and 0.0% in Nanays; 1.5 and 0.0% in eastern Evenks; no deletions and insertions of such type were revealed in western Evenks, and also in Mansi, Yakuts, Chukcha and Eskimos. Correlation analysis of the data about the populations from Siberia, foreign Asia and Oceania revealed a geographical gradient of the deletion frequency which increases towards the East. The azimuth of the deletion frequency geographical gradient direction is 170 degrees. The deletion frequency gradient (Z) within the limits from the subarctic regions of Siberia to the west regions of Oceania is described quite completely with the multiple regression equation: Z = 30.516 - 0.840 (latitude) + 0.145 (longitude). The part of geographical factor within the total variability of the deletion frequency is 64%. The regularity discovered does not extend to the indian population of America.
Using the method for polymerase chain reaction the polymorphism of eight markers of the nuclear DNA was studied. In a sample of Russians taken at random (N = 118) from predominantly southern and central regions of Russia, allele frequencies were determined for restriction sites HindIII at HBG-2 and PAH loci, AvaII at the HBB locus, MspI at the ApoB locus, PstI at D7S8, HincII at LDLR, TaqI and BamHI at the DSX164. Comparative data for different world regions are presented.
The geographical distribution of the Asian specific deletion--insertion polymorphisms and or the RFLP's in the V noncoding region and the D-loop and of the mitotypes was analysed in Mongolia. The frequencies of the mtDNA markers demonstrated homogeneity of 18 local groups in Mongolia. The geographical distribution of the mitotypes showed the existence of two ancestral maternal lineages in mongols. There was no significant difference in the average FST values between mitochondrial gene flow and the nuclear gene flow of the Mongolian population. The equality of FST values permit to calculate the mutation rate for the human mtDNA--6.10(-9) per nucleotide per year. The data reveals the Mongolian population is in the equilibrium.