The genetic heterogeneity of hereditary human diseases]

The paper deals with the probability regularities of mutations arising in the same locus (or nucleotide) in human populations. It is shown that in a population of constant size the number of such recurrent mutations tends to an equilibrium value. It is demonstrated that dynamics of this number of recurrent mutations depends on the population structure essentially. This phenomenon is illustrated by comparing non-subdivided and hierarchy populations of the same size.     

Ecological aspects of polymorphism in an African land snail, Limicolaria martensiana

In Uganda the herbivorous land snail, Limicolaria martensiana occurs in well-defined populations. Samples of snails from 49 populations reveal the existence of five distinct colour forms, the frequency of which varies markedly from population to population. There is a common streaked form that occurs in all populations and a series of pallid forms that may be present or absent. Late Pleistocene fossils from the Western Rift indicate that the polymorphism is at least 8000–10,000 years old. The polymorphism is not correlated with broad geographical components of the environment or with habitat. It is however correlated with population density, and in one population a change in density resulted in a change in the relative frequency of the colour forms. Human activities have probably contributed to the dispersal of the snails to new areas, and because of these the founder effect cannot be ruled out as contributing to the polymorphism.     

Genetic load and coadaptation of chromosomal inversions. II. O-chromosomes in Drosophila subobscura populations

We have analysed the inversion polymorphism and genetic load of O-chromosomes in three populations of D. subobscura from southeastern Europe. As expected for a central populations the inversion polymorphism was extensive. In a like fashion, the genetic load, in particular the frequency of lethals, was heavy in all three populations. There were significant differences in the frequency of moderately deleterious genes. These differences in viability can be attributed to balancing selection. A comparison of these two kinds of genetic polymorphism indicates that there are differences in mean viability among different gene arrangements of O-chromosomes in the three populations. The differences observed are due to an unequal distribution of various viability classes among O-chromosome gene arrangements. We here show for the first time a specific distribution of lethal genes among these arrangements within the Palearctic distribution area of D. subobscura. The lethal allelism test showed lethals are non-randomly associated with the Ost gene arrangement. The amount of genetic load is heavy in gene arrangements with a high frequency, in comparison with the ones with a low frequency. Lethal genes may be protected in combinations of low and moderate frequency gene arrangements that harbor more lethal genes, as the Ost in the one population. Some arrangements that are less protected against recombination have a higher load than ones that are more protected against recombination. This can be taken as evidence for coadaptation.     

Loss of genetic variation in declining populations of Aricia artaxerxes in Northern Hungary

Rapid decline of population size often gives rise to loss of genetic variation and may result in a reduction in fitness. It is, therefore, essential to detect past demographic changes in populations of endangered species. Aricia artaxerxes occurs in two regions of Northern Hungary: Bükk Mts. and the Aggtelek Karst region. The species prefers short-grass habitats, which are subject to succession. Due to climatic differences between the two regions succession is more rapid in the Bükk plateau resulting in the decline and isolation of A. artaxerxes populations there. In contrast, most populations have remained rather large and stable in the Karst region. This situation provides an excellent possibility to compare the genetic composition of stable and declining populations. A. artaxerxes was collected in four populations of the Bükk Mountains and in ten in the Aggtelek Karst region in 2002 and 2005. We analysed 19 polymorphic allozyme loci in all samples. The results revealed an extremely high level of enzyme polymorphism in A. artaxerxes. Most parameters of polymorphism proved to be significantly higher in the Karst region compared to the Bükk. The shape of the distribution of alleles among the frequency classes indicated the effect of bottleneck in three Bükk and one Karst population. Though heterozygote excess was only significant in one Bükk population a tendency was observed for higher values of standardised heterozygote excess in those populations that had a typical bottleneck distribution of alleles. Our results clearly demonstrated that those populations/subpopulations that compose a network with intense migration are able to maintain their genetic diversity in a long run, while the isolated small populations of the Bükk plateau have lost a sizeable part of their variation.     

Genetic variation in populations of the endangered fish Ladigesocypris ghigii and its implications for conservation

1. The genetic variation of the endangered freshwater fish Ladigesocypris ghigii, endemic to the island of Rhodes (Greece), was investigated for nine populations, originating from seven different stream systems and a reservoir, both at the mtDNA and nuclear level, in order to suggest conservation actions. 2. Both restriction fragment length polymorphism analysis of five segments of mitochondrial DNA (ND‐5/6, COI and 12S‐16S rRNA) amplified by polymerase chain reaction, and random amplified polymorphic DNA analysis, revealed extremely low levels of intra‐population polymorphism. It is highly likely that the low intra‐population variability is the result of successive bottleneck events evident in shrinkage and expansion of the populations year after year, which may have led to a complete loss of several genotypes and haplotypes, and an increased degree of inbreeding. 3. Inter‐population genetic structuring was high, with fixation of haplotypes within six of the nine populations and fixation of alleles within populations originating from different waterbodies. It is probable that all haplotypes and/or alleles found were initially represented in all populations. However, because of the long time of isolation coupled with successive bottleneck and subsequent genetic drift, common mtDNA haplotypes and alleles among the populations may have become rare or extinct through stochastic lineage loss. 4. Although nucleotide divergence among haplotypes was very shallow, half of the haplotypes recorded (three of six), resulted from nucleotide changes on the 12S–16S rRNA segments, which are the most conserved part of the mitochondrial genome. This fact may indicate that the observed genetic variation did not necessarily result only from the retention of ancestral polymorphism, but may have arisen through mutation and complete lineage sorting over a relatively small number of generations, once the populations had become isolated from one another. 5. Our data suggest that two of the L. ghigii populations may be on independent evolutionary trajectories. Considering that each population appears so far well adapted within each site, all populations should be managed and conserved separately.     

Infraspecific diversity of Cytisus emeriflorus Reichenb. (Leguminosae), an endemic plant with disjunct distribution: Evidence from isozyme data

ABSTRACT

C. emeriflorus is an endemic species occurring in two disjunct areas some 200 km apart: the Pre-Alps of Lombardia and the Pre-Alps of Friuli. Four populations from the western area and five populations from the eastern area were sampled in order to ascertain the amount and the distribution of variation throughout the range of the species. Phenetic measures of isozyme polymorphism were used. Diversity values showed that the species is polymorphic, despite its restricted distribution and the small population size; phenetic distances revealed that partitioning of diversity was largely within rather than among populations. Moreover, little differentiation was found between the two disjunct areas, although the western populations exhibited a slightly higher diversity compared with the eastern ones. The high level of polymorphism and the overall similarity between populations from the two areas may be ascribed to past contacts, and indicate that, despite the present widespread disjunction, the two areas have not evolved independently long enough for divergence to have occurred. There is no evidence that C. emeriflorus is at present genetically depauperated, although its range of distribution must have been much broader in the past; its present reduced distribution area and the small population size may be mainly due to ecological factors.     

Subdivision and haplotype structure in natural populations of Arabidopsis lyrata

High levels of inbreeding are expected to cause a strong reduction in levels of genetic variability, effective recombination rates and in adaptation compared with related outcrossing populations. We examined patterns of DNA polymorphism at five nuclear loci and one chloroplast locus within and between four populations of the outcrossing plant Arabidopsis lyrata, a close relative of the highly self-fertilizing model species A. thaliana. The observed patterns are compared with species-wide polymorphism at orthologous loci, as well as within- and between-population patterns at other studied loci in A. thaliana. In addition to evidence for much higher average within-population diversity, species-wide levels of silent polymorphism are generally higher in A. lyrata than in A. thaliana, unlike the results from a previous study of the ADH locus. However, polymorphism is also low in the North American A. lyrata subspecies lyrata compared with the European subspecies petraea, suggesting either a population bottleneck in North American populations or recent admixture involving diverged European populations. Differentiation between the two subspecies is strong, although there are few fixed differences, suggesting that their isolation is recent. Estimates of intralocus recombination rates and analysis of haplotype structure in European A. lyrata populations indicate lower recombination than predicted based on the variability together with physical recombination rates estimated from A. thaliana. This may be due to strong population subdivision, or to recent departures from demographic equilibrium such as a bottleneck or population admixture. Alternatively, there may be consistently lower recombination rates in the outcrossing species. In contrast, estimates of recombination rates from species-wide samples of A. thaliana are close to the values expected assuming a high rate of self-fertilization. Complex population histories in both A. thaliana and A. lyrata complicate theoretical predictions and empirical tests of the effects of inbreeding on polymorphism and molecular evolution.     

Insertional polymorphism of a non-LTR mobile element (NLRCth1) in European populations of Chironomus riparius (Diptera, Chironomidae) as detected by transposon insertion display.

The midge Chironomus riparius is distributed all over the Palearctic region and is well characterized both at the morphological and cytogenetic levels. Here we describe a population study based on the insertional polymorphism of the retroposon NLRCth1, by means of a S-SAP (sequence-specific amplification polymorphism) derived technique (transposon insertion display; TID). While a previous study of allozyme polymorphism in Russian samples showed little variability, all the amplicons we identified are polymorphic. Genetic distances between 6 natural populations were calculated according to Nei and did not show a positive correlation with geographic distances. The genetic diversity detected among individuals of a given population was one order of magnitude higher than that among populations. However, the value of phi(ST) was significant (p < 0.001) and indicates that natural populations are more genetically differentiated than random samples of individuals.     

Analysis of genetic diversity in red clover (Trifolium pratense L.) breeding populations as revealed by RAPD genetic markers.

Red clover is an important forage legume species for temperate regions and very little is known about the genetic organization of its breeding populations. We used random amplified polymorphic DNA (RAPD) genetic markers to address the genetic diversity and the distribution of variation in 20 breeding populations and cultivars from Chile, Argentina, Uruguay, and Switzerland. Genetic distances were calculated for all possible pairwise combinations. A high level of polymorphism was found and the proportion of polymorphic loci across populations was 74.2%. A population derived from a non-certified seedlot displayed a higher proportion of polymorphic loci than its respective certified seedlot. Gene diversity values and population genetics parameters suggest that the populations analyzed are diverse. An analysis of molecular variance (AMOVA) revealed that the largest proportion of variation (80.4%) resides at the within population level. RAPD markers are a useful tool for red clover breeding programs. A dendrogram based on genetic distances divided the breeding populations analyzed into three distinct groups. The amount and partition of diversity observed can be of value in identifying the populations that parents of synthetic cultivars are derived from and to exploit the variation available in the populations analyzed.     

MHC diversity in bottlenecked populations: a simulation model

The depletion of variation at MHC loci, which play a crucial role in pathogen recognition, has been postulated to be one of important extinction risk factors for endangered populations. Thus, it is important to understand how selection affects the level of polymorphism in these genes when populations undergo a reduction in size. We followed MHC diversity in computer simulations of population bottlenecks. The fates of MHC alleles in the simulations were determined either by drift, or by balancing selection resulting from host–parasite coevolution. We found that the impact of selection on MHC polymorphism in bottlenecked populations was dependent upon the timescales involved. Initially, selection maintained lower number of alleles than drift, but after ~40 generations of hosts selection maintained higher MHC diversity, as compared to drift. The adverse effects of decreased MHC polymorphism on population viability may be, to some extent, compensated for if selection helps to retain MHC alleles which show high functional diversity, which should allow protection against a broader range of pathogens. Our simulation shows, however, that the mean divergence of alleles retained under selection in bottlenecked populations is not, on average, significantly higher than the divergence due to drift.     

Is There Selection on RFLP Differences in Mitochondrial Dna?

Experimental populations of Drosophila simulans were established for the purpose of detecting the presence or absence of selection on a restriction fragment length polymorphism in mitochondrial DNA (mtDNA). It was then discovered that the founding strains differed with respect to the Rickettsia-mediated incompatibility system in this species, which is maternally transmitted together with the mtDNA differences. A population model was constructed using the known fitness effects of the incompatibility system, with the result that the population trajectories can be completely explained by the effects of the microorganism with no need to invoke selection on mtDNA. The strong conclusion is that in this case we can rule out the strong selection proposed by MacRae and Anderson to explain the "dramatic mtDNA changes" in their Drosophila pseudoobscura populations. The population theory used for the experiments is discussed in the context of natural populations. Estimated parameters include the possibility that with two populations, one with the organism and one without it, there may be no bias as to which will invade the other, which in turn suggests no global tendency for the infection to spread or decline.     

Enzyme gene heterozygosity in small island populations of Philaenus spumarius (L.) (Homoptera)

Genetic polymorphism at about twenty enzyme loci in one mainland and in six differentially isolated island populations of Philaenus spumarius (L.) was studied by starch gel electrophoresis. The populations have different average degrees of heterozygosity, so that the most isolated population is the least polymorphic. The differences in heterozygosity seem to be correlated to the size of the population and the degree of isolation from other populations. With a single exception, the most common allele in each locus is the most common one everywhere. The results are compared with the differences observed in the color polymorphism of Philaenus island populations. The allele frequencies of enzyme loci are maintained by selection; the fact that the prevalent allele is the same in all populations may be due to selection and founder principle.Report no. 485 from the Tvärminne Zoological Station, University of Helsinki.     

广东地区汉族群体线粒体DNA 9bp序列缺失频率研究

旨在研究中国广东省部分地区汉族人群线粒体DNA RegionⅤ9bp序列缺失情况.采用PCR-PAGE和直接测序法对3个群体144份样本mtDNA RegionⅤ进行序列分析.结果只检测到标准型和短型(即9 bp缺失)两种多态.广东汉族人群的平均缺失频率为21.5%,广州、东莞和湛江汉族人群的缺失频率依次为20.8%、19.2%和25.0%.由此得出,广东汉族人群mtDNA 9 bp缺失频率较高,与其它地区汉族群体存在一定的差异.     

Mitochondrial iso-citrate dehydrogenase variation in the Australian bush-rat, Rattus fuscipes greyii

Four reproductively isolated populations of the Australian bush-rat, Rattus fuscipes greyii , are polymorphic for electrophoretic variants of the mitochondrial enzyme, NADP-dependent iso-citrate dehydrogenase (M-Idh). The electrophoretic patterns of M-Idh and a small amount of breeding data are in agreement with the hypothesis that the variation is controlled by two alleles at an autosomal locus, Idh-2. In three relatively large populations, the proportion of heterozygotes at the Idh-2 locus ranges from 0.07 to 0.23, while on a small off-shore island it is 0.60. In this latter population there is an excess of heterozygotes which is on the borderline of statistical significance, suggesting that heterotic selection may be maintaining the polymorphism. Populations on eight other small islands are monomorphic for the allele which is the most frequent in the large populations. In most species M-Idh is less variable than most other enzymic proteins and the results presented here constitute one of the few published examples of an extensive M-Idh polymorphism.     

Relationship between Migration and DNA Polymorphism in a Local Population

The expected amount of DNA polymorphism, measured in terms of the number of nucleotide differences between the two DNA sequences randomly sampled from subpopulations, was studied by using the stepping-stone model and the finite island model, under the assumption that the migration rate is not the same among different subpopulations. The results obtained indicate that the expected amount of DNA polymorphism in the subpopulation with lower migration rate is smaller than that of higher migration rate. This suggests that marginal populations tend to have lower level of DNA polymorphism than central populations if the migration rate in the marginal populations is lower than that of the central populations.     

The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus

The dopamine D4 receptor gene (DRD4) has an expressed polymorphism in the third exon that may have functional relevance. The polymorphism exists at two levels. At the higher level there is an imperfect tandem repeat of 48 base pairs (bp) coding for 16 amino acids; alleles have been identified with 2 (32 amino acids) to 10 (160 amino acids) repeats. The imperfect nature of the repeats is responsible for a more subtle level of variation since alleles with the same number of repeats can differ in the exact sequences or in the order of the variants of the 48-bp unit. We have undertaken a global survey of this expressed polymorphism as one approach to understanding the evolutionary significance and origins of the polymorphism as well as understanding what selective forces, if any, may be operating at this locus. As the first step, we have determined the repeat number genotype of the DRD4 repeat polymorphism in 1,327 individuals from 36 different populations. The allele frequencies differ considerably among the different populations. The 4-repeat allele was the most prevalent (global mean allele frequency = 64.3%) and appeared in every population with a frequency ranging from 0.16 to 0.96. The 7-repeat allele was the second most common (global mean = 20.6%), appearing quite frequently in the Americas (mean frequency = 48.3%) but only occasionally in East and South Asia (mean frequency = 1.9%). The 2-repeat allele was the third most common (global mean frequency = 8.2%) and was quite frequent in East and South Asia (mean frequency = 18.1%) while uncommon in the Americas (mean frequency = 2.9%) and Africa (mean frequency = 1.7%). The universality of the polymorphism with only three common repeat-number alleles (4, 7, and 2) indicates that the polymorphism is ancient and arose before the global dispersion of modern humans. The diversity of actual allele frequencies for this expressed polymorphism among different populations emphasizes the importance of population considerations in the design and interpretation of any association studies carried out with this polymorphism. Received: 18 July 1995 / Revised: 18 December 1995     

赣中南花猪随机扩增多态DNA与群体遗传关系的研究

用RAPD技术检测了泰和冠朝猪、永丰藤田花猪、瑞金三花猪、兴国茶园猪、上犹花猪、万安花猪、乐安花猪等7个赣中南花猪地方类群基因组混合DNA的多态性,经80个随机引物扩增筛选,16个引物产生了共44个多态标记。遗传距离指数计算结果显示：泰和冠朝猪和瑞金三花猪亲缘关系最近,而兴国茶园猪与乐安花猪遗传距离最远。各类群的UPMGA和NJ聚类分析结果与采用生化、免疫和细胞遗传标记分析的结论不尽相同,在此基础上,结合现行分类方法,认为各受试猪群可暂时归并为赣中南花猪类型,但对泰和冠朝猪和万安花猪的品种归属性应作进一步分析。 Abstract: Random amplified polymorphic DNAs (RAPDs) were used to investigate bulked genomic DNA polymorphism of seven pig populations including Taihe Guanchao,Yongfeng Tengtian Spotted,Ruijin Spotted,Xingguo Chayuan,Shangyou Spotted,Wanan Spotted,and Lean Spotted pig.Eighty random primers were screened,of them,16 primers generated polymorphic markers with total number of 44.The genetic distance index matrix indicated that the genetic relationship between Taihe Gaunchao and Ruijin Spotted pig population was the closest,while that between Xingguo Chayuan and Laan Spotted pig population was the farthest.Our molecular phylogenetic trees constructed by UPMGA and NJ methods were in general consistent with that based on biochemical,immunogenetic and cellular genetic markers except for differences in some populations.It was inferred from this study that all pig populations examined could be temporary classified into one breed,however,the population genetic character of Taihe Guanchao and Wanan Spotted pig populations should be further evaluated.     

Allelic genealogy and human evolution

Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected. Extraordinary polymorphism at some loci of the major histocompatibility complex (Mhc) rules out the past action of severe bottlenecks, or the so-called founder principle, which invokes only a small number of founding individuals when a new species emerges. This conclusion may be extended to the 35-Myr-old history of the human lineage, because some polymorphism at Mhc loci seems to have lasted that long. Furthermore, although the population structure prior to the late Pleistocene is less clear, owing to the insensitivity of Mhc alleles, even to low levels of migration, the nature of Mhc polymorphism suggests that the effective size of populations leading to humans was as large as 10(5). Hence, the effective population size of humans might have become somewhat smaller in most of the late Pleistocene. The reduction could be due either to the then adverse environment in the Old World and/or to the increased migration rate. It is also argued that population explosion fostered by the agriculture revolution has had significant effects on incorporating new alleles into human populations.      

Amplified fragment length polymorphism analysis of Mythimna separata (Lepidoptera: Noctuidae) geographic and melanic laboratory populations in China

Genetic diversity within and among three wild-type natural populations and one melanic laboratory population of Mythimna separata (Walker) (Lepidoptera: Noctuidae) were evaluated using amplified fragment length polymorphism (AFLP) analysis. Although extensive genetic diversity occurs among individuals from different geographic populations (P = 54.5%, h = 0.209, I = 0.305), the majority of the genetic diversity is within populations and not between populations (G(ST) = 0.172), indicating high gene flow (N(M) = 2.403) and suggesting that M. separata in northern China are a part of a single large metapopulation. Genetic diversity in the natural populations was significantly higher than that in the melanic laboratory population (with P = 43.4% versus P = 25.9%, h = 0.173 versus h = 0.086, and I = 0.251 versus I = 0.127), suggesting that the melanic laboratory population is narrowly genetic-based and genetically uniform. Genetic similarities based on AFLP data were calculated, and cluster analysis was preformed to graphically display groupings between individuals and populations. Individuals from the same region were not grouped together in cluster analysis of three natural populations, whereas melanic individuals from laboratory population were grouped together very well. Four subpopulations were clustered into two broad groups. Melanic laboratory population became a single group, which had apparent differentiation from the other group in which three natural subpopulations were included. These results indicated that although high genetic variability existed among the individuals of natural populations, there was little genetic differentiation among three geographic populations that could be explained by the effects of the long distance migration of the oriental armyworm in China enhanced the level of gene flow. Influences of migration on the genetic polymorphism and differentiations that make a significant contribution to evolution in this insect are reviewed.     

Conservation genetics of the threatened horned grebe (<Emphasis Type="Italic">Podiceps auritus</Emphasis> L.) population of the Magdalen Islands,Québec

The horned grebe (Podiceps auritus) population of the Magdalen Islands in the St. Lawrence Gulf (Québec, Canada) has declined sharply over the last decades. It is the only breeding population of this species in eastern North America with nearest breeding populations being >2500 km apart in western North America and Europe, We used three types of genetic markers: mitochondrial (mt) DNA ND2 sequence, α-enolase intron sequence, and 25 amplified fragment length polymorphism loci (AFLPs) to quantify the genetic diversity within the Magdalen Island population and to assess its genetic distinctiveness relative to populations from western Canada (five sites) and Iceland (one site). The Magdalen Island population retained a comparable amount of genetic diversity to the average diversity observed across all populations in all three markers. Horned grebe mtDNA sequences formed a monophyletic group and nearly all haplotypes present in Québec were found elsewhere. In the ND2 fragment, populations partitioned into two groups corresponding to subspecies (Iceland versus North American sites) and more strongly in three groups according to geographic disjunctions (Iceland versus Québec versus western Canada). In contrast, there was no evidence of structure between sites in the α-enolase intron. In the AFLPs, Iceland showed the greatest level of differentiation, followed by the Québec and British Columbia populations. For conservation purposes, we suggest that the Magdalen Islands population should be recognized as a separate unit.