Mouse haemoglobin Beta chains. Sequence data on embryonic y chain and genetic linkage of the Y-chain locus to the adult beta-chain locus Hbb.

Embryonic haemoglobin y-chain types were determined by starch-gel electrophoresis for inbred Mus musculus strains Sec/ReJ and Au/SsJ (with Hbbs and Hbbp adult beta-chain alleles respectively) and for random-bred HA/ICR (Swiss) mice, which had been selected to be homozygous for the adult Hbbd beta-chain allele. The strain with the Hbbs allele had y1 embryonic beta chain and the strain with the Hbbd allele had y2. The strain with the Hbbp allele also had y2 chain. A breeding study showed that the maximum recombination frequency between the Hbb locus and the y-chain locus is 5.4% at the 95% confidence level. Embryonic y2 chain was sequenced for 39 positions from the N-terminus with an Edman-Begg sequenator. Some tryptic-peptide composition data were obtained on both y1 and y2 chains. No amino acid substitutions between y1 and y2 chains were found in the 40 positions for which there are common data on the two chains. y2 and adult beta chains are different in 12 of the first 21 positions, but show considerable similarity thereafter. It is suggested that homologous but unequal crossing-over between y-chain and adult beta-chain loci could have given rise to the adult beta-chain allele Hbbd, which produces structurally different major and minor beta chains from two closely linked genes.     

A new haplotype of the beta-globin gene complex, Hbbw1, in Chinese wild mouse

A new pattern was observed in the electrophoretic survey of the hemoglobin beta chain (Hbb) in Chinese wild mice, Mus musculus. The electrophoretic mobility of the major component of the new Hbb was identical to that of Hbbs on cellulose acetate plate, although it was almost identical to that of Hbbd or Hbbp on acrylamide gel. This suggests that the major component of Chinese Hbb has a unique primary structure. A minor component of the new Hbb was completely different from that of the other three Hbb haplotypes well known. These results indicate that the Hbb-b1 and Hbb-b2 of the new Hbb haplotype, assigned Hbbw1, are unique genes in their molecular structure. So far, Hbbw1 has been observed in northwestern China.     

Use of a new mouse beta-globin haplotype (Hbbs2) to study hemoglobin expression during development

Mice of the mutant haplotype (Hbbs2) produce a variant beta-s globin (beta-s2major) which can be distinguished from beta-smajor and beta-sminor by cellulose acetate electrophoresis and ion exchange chromatography. Mice homozygous for this mutation were used to study the relative quantities of the mutant beta-s2major and normal beta-sminor globins specified by the two adult beta-globin genes of the Hbbs2 haplotype during development. At 11.5 days of gestation, beta-s2major comprises under 20% and beta-sminor over 80% of the adult beta-globin. The relative level of beta-sminor decreases through fetal development; at birth beta-sminor represents 33.7% of the beta-globin. The adult value of 71.0% beta-s2major and 29.0% beta-sminor globin is expressed in mice 6 days after birth. In mildly anemia alpha-thalassemic heterozygotes (Hbab2(th)/Hbab;Hbbs2/Hbbs2) the level of beta-sminor globin increases from 29.0 to 37.9%, but beta-sminor is elevated only slightly (29.0 to 33.9%) in asymptomatic beta-thalassemic heterozygotes (Hbab/Hbab;Hbbd3(th)Hbbs2). The relative quantity of beta-sminor is increased significantly (29.0 to 41.4%) in doubly heterozygous alpha-thalassemic, beta-thalassemic mice (Hbab2(th)/Hbab;Hbbd3(th)/Hbbs2). The relative levels of expression of the beta 1s2major and beta 2sminor globin genes of Hbbs2/Hbbs2 mice correlates well with the expression of the beta 1dmajor and beta 2dminor globin genes of Hbbd/Hbbd mice during development and in response to hematological stress caused by thalassemia. Expression of the beta 1sminor globin gene should not have been affected by the ENU-induced base substitution in the beta 1smajor gene. Therefore, we propose that the beta 1sminor gene is also expressed in mice of the Hbbs haplotype. The results also indicated that the two adult beta-globin genes of the Hbbs2 and, presumably, of the Hbbs haplotypes are regulated independently as are the beta 1dmajor and beta 2dminor genes of the Hbbd and Hbbp haplotypes.     

Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice

When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is replaced by the Y of certain strains of Mus musculus domesticus, testis determination fails and all XY fetuses develop either as hermaphrodites or XY females (XY sex reversal). This suggests the presence of at least two alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6. The B6 Y chromosome is derived from the Japanese house mouse, M. m. molossinus and therefore carries a molossinus Sry allele. As a first step to determine how the molossinus Sry allele evolved, its distribution pattern was determined in wild mice. The cumulative data of 96 M. musculus samples obtained from 58 geographical locations in Europe, North Africa, and Asia show the molossinus Sry allele is restricted to Japan and the neighboring Asian mainland and confirm that Japanese M. m. molossinus mice were derived in part from a race of M. m. musculus from Korea or Manchuria. Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve as molecular markers for studies on the evolution of wild M. musculus populations and can help determine the role sex determination plays in speciation.      

Low variability of the POLG (CAG)n repeat in north Eurasian populations

We investigated the frequency of different repeat-length alleles of the trinucleotide CAG microsatellite repeat in the coding sequence of the nuclear gene for the catalytic subunit of mitochondrial DNA polymerase gamma (POLG) in 12 ethnic groups from northern Eurasia. The population sample consisted of 1,330 individuals from 3 large geographic areas: Europe, Southwest Asia, and Siberia/East Asia. We found that the 10-repeat allele of the POLG gene is the most frequent in all analyzed populations, with a frequency of 88-96%. The heterozygosity level ranges from 22% in Europe to 13.6% in Southwest Asia with the lowest value of 7.4% in Siberia/East Asia. The present study provides evidence of clinal distribution of POLG gene heterozygosity in North Eurasian populations. In general, we found an extremely low variability of the trinucleotide CAG microsatellite repeat, suggesting that purifying selection acts against deleterious alleles, although low mutability of the repeated region cannot be ruled out.     

The geographic spread of the CCR5 Delta32 HIV-resistance allele

The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10%) for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.     

Geographically separate increases in the frequency of the derived ADH1B*47His allele in eastern and western Asia

The ADH1B Arg47His polymorphism has been convincingly associated with alcoholism in numerous studies of several populations in Asia and Europe. In a review of literature from the past 30 years, we have identified studies that report allele frequencies of this polymorphism for 131 population samples from many different parts of the world. The derived ADH1B*47His allele reaches high frequencies only in western and eastern Asia. To pursue this pattern, we report here new frequency data for 37 populations. Most of our data are from South and Southeast Asia and confirm that there is a low frequency of this allele in the region between eastern and western Asia. The distribution suggests that the derived allele increased in frequency independently in western and eastern Asia after humans had spread across Eurasia.     

The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.     

Haemoglobin variants in mice.

Haemoglobin variants were studied in wild and laboratory house mice (Mus musculus), including standard and new inbred strains, using starch-gel electrophoretic technique. Single (Hbbs) or diffuse (Hbbd) types of haemoglobin were found in all of them. The embryonic haemoglobin pattern was different from although similar to that of the adult in all the strains. The haemoglobins revealed monomorphism in the inbred strains, while polymorphism was observed in non-inbred laboratory and wild mice.     

Analysis of wild-derived mice for Fv-1 and Fv-2 murine leukemia virus restriction loci: a novel wild mouse Fv-1 allele responsible for lack of host range restriction.

Wild-derived mice originally obtained from Asia, Africa, North America, and Europe were typed for in vitro sensitivity to ecotropic murine leukemia viruses and for susceptibility to Friend virus-induced disease. Cell cultures established from some wild mouse populations were generally less sensitive to exogenous virus than were cell cultures from laboratory mice. Wild mice also differed from inbred strains in their in vitro sensitivity to the host range subgroups defined by restriction at the Fv-1 locus. None of the wild mice showed the Fv-1n or Fv-1b restriction patterns characteristic of most inbred strains, several mice resembled the few inbred strains carrying Fv-1nr, and most differed from laboratory mice in that they did not restrict either N- or B-tropic murine leukemia viruses. Analysis of genetic crosses of Mus spretus and Mus musculus praetextus demonstrated that the nonrestrictive phenotype is controlled by a novel allele at the Fv-1 locus, designated Fv-10. The wild mice were also tested for sensitivity to Friend virus complex-induced erythroblastosis to type for Fv-2. Only M. spretus was resistant to virus-induced splenomegaly and did not restrict replication of Friend virus helper murine leukemia virus. Genetic studies confirmed that this mouse carries the resistance allele at Fv-2.     

The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.     

Population genetics of the Malm? polymorphism of coagulation factor IX.

The distribution of 1,198 Malm? alleles was examined in 822 men from 16 indigenous populations and 188 women from 7 of the ethnic groups. Subjects were from several European countries, the Mediterranean, East Asia, and the USA (Anglo- and African-Americans). The frequencies of the rarer (Malm? B) allele were approximately equal across Europe, the highest frequencies (0.36) being in the French and Anglo-Americans; no population was observed with clearly the highest frequency. They diminished slightly at moderate distances from Europe (Tunisia, Ethiopia) and greatly at longer distances (East Asia and West Africa). In Orientals, the frequencies ranged from 0.07 (East Indians) to 0.03 (the Chinese) and from 0.0 to 0.15 in African-Americans. Assuming selective neutrality, the data are consistent with the European origin of the 'B' allele when the population was small and outward spread.     

Specific Frequency Distribution of Erythrocytic X-Protein Alleles in Indigenous Sheep Populations in East Asia

The nonhemoglobin erythrocytic X-protein polymorphism consisting of two phenotypes called X-positive [X(+)] and X-negative [X(-)] was determined in 576 unrelated healthy native sheep of East Asia, using one-dimensional and horizontal starch gel electrophoresis. A striking difference in the frequency of the X allele coding dominantly for the X(+) type between the northern and southern populations of native East Asian sheep divided by the boundary of the Himalaya Mountains was seen (P < 0.0001). The X allele frequency ranged from 0 to 0.0438 with an average of 0.0323 in the northern population examined, consisting of the Bhyanglung, Baruwal, Yunnan, and Khalkhas sheep belonging to the Tibetan and Mongolian sheep groups. In contrast, the frequency of the same allele was in the range of 0.2037-0.4655 and the mean frequency was 0.2998 in the southern population tested, consisting of the Bengal, Kagi, Lampuchhre, Vietnamese, and Myanmar sheep, which belong to the Indian sheep group. This finding suggests that the X allele appears to be an Indian sheep marker and is potentially important in phylogenetic studies on native sheep populations, especially in East Asia.     

Allele variation of DYS19 and Y-Alu insertion (YAP) polymorphisms in Basques: an insight into the peopling of Europe and the Mediterranean region

Two Y-chromosome DNA polymorphisms, the DYS19 microsatellite and the YAP (at locus DYS287), were tested in males from two autochthonous Basque populations from France and northern Navarre (Spain). The results are compared to those obtained for the same genetic markers in 32 populations from Europe, northern Africa, and western Asia. The high predominance of the DYS19*11 (190-base-pair) allele in Basques indicates that their genetic diversity for microsatellite DYS19 is around half that observed in Europeans, North Africans, and western Asians. The Y-Alu insertion (YAP+) was not detected in the Basque samples. This study attempts to throw some light on the importance of historically recent migratory movements, the main corridors of gene flow, and demographic sizes and their variations in shaping gene frequency patterns in contemporary human populations, particularly in the Mediterranean region. Historical processes may have had more significant effects on the genetic make-up of current human populations than those of prehistoric times.     

On the Distribution and Origin of Salix in the World

1. The distribution of Salix species among the continents. There are about 526 species of Salix in the world, most of which are distributed in the Northern Hemisphere with only a few species in the Southern Hemisphere. In Asia, there are about 375 species, making up 71.29 percent of the total in the world, including 328 endemics; in Europe, about 114 species, 21.67 percent with 73 endemics; in North America, about 91 species, 17.3 percent with 71 endemics; in Africa, about 8 species, 1.5 percent, with 6 endemics. Only one species occurs in South America. Asia, Europe and North America have 8 species in common (excluding 4 cultivated species). There are 34 common species between Asia and Europe, 14 both between Europe and North America and between Asia and North America, 2 between Asia and Africa. Acording to the Continental Drift Theory, the natural circumstances which promoted speciation and protected newly originated and old species were created by the orogenic movement of the Himalayas in the middle and late Tertiary. Besides, the air temperature was a little higher in Asia than in Europe and North America (except its west part) and the dominant glaciers were mountainous in Asia during the glacial epoch in the Quaternary Period. Then willows of Europe moved southwards to Asia. During the interglacial period they moved in opposite direction. Such a to-and-fro willow migration between Asia and Europe and between and North America occurred so often that it resulted in the diversity of willow species in Asia. Those species of willows common among the continents belong to the Arctic flora. 2. The multistaminal willows are of the primitive group in Salix. Asia has 28 species of multistaminal willows, but Europe has only one which is also found in Asia. These 28 species are divided into two groups, “northern type” and “southern type”, according to morphology of the ovary. The boundary between the two forms in distribution is at 40°N. The multistaminal willows from south Asia, Africa and South America are very similar to each other and may have mutually communicated between these continents in the Middle or Late Cretaceous Period. The southern type willows in south Asia are similar to the North American multistaminal willows but a few species. The Asian southern type willows spreaded all over the continents of Europe, Asia and North America through the communication between them before the Quaternany Period. Nevertheless, it is possible that the willows growing in North America immigranted through the middle America from South America. The Asian northern type multistaminal willows may have originated during the ice period. The multistaminal willows are more closed to populars in features of sexual organs. They are more primitive than the willows with 1-3 stamens and the most primitive ones in the genus. 3. The center of origin and development of willows Based on the above discussion it is reasonable to say that the region between 20°-40°N in East Asia is the center of the origin and differentiation of multistaminal willows. It covers Southern and Southwestern China and northern Indo-China Pennisula.     

Biochemical diversity and evolution in the genus Mus

Thirteen biochemical groups of wild mice from Europe, Asia, and Africa belonging to the genus Mus are analyzed at 22–42 protein loci. Phylogenetic trees are proposed and patterns of biochemical evolution are discussed, as well as the possible contribution of wild mice to the genetic diversity of laboratory stocks.     

Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing

Wilson disease is an autosomal recessive inherited disorder of copper metabolism. The Wilson disease gene codes for a copper transporting P-type ATPase (ATP7B). Molecular genetic analysis reveals at least 300 distinct mutations. While most reported mutations occur in single families, a few are more common. The most common mutation in patients from Central, Eastern, and Northern Europe is the point mutation H1069Q (exon 14). About 50–80% of Wilson disease (WD) patients from these countries carry at least one allele with this mutation with an allele frequency ranging between 30 and 70%. Other common mutations in Central and Eastern Europe are located on exon 8 (2299insC, G710S), exon 15 (3400delC) and exon 13 (R969Q). The allele frequency of these mutations is lower than 10%. In Mediterranean countries there is a wide range of mutations, the frequency of each of them varies considerably from country to country. In Sardinia, a unique deletion in the 5′ UTR (−441/−427 del) is very frequent. In mainland Spain the missense mutation M645R in exon 6 is particularly common. Data from non-European countries are scarce. Most data from Asia are from Far Eastern areas (China, South Korea and Japan) where the R778L missense mutation in exon 8 is found with an allele frequency of 14–49%. In summary, given the constant improvement of analytic tools genetic testing will become an integral part for the diagnosis of WD. Knowledge of the differences in the worldwide distribution of particular mutations will help to design shortcuts for genetic diagnosis of WD.     

The structure of wild and domesticated emmer wheat populations,gene flow between them,and the site of emmer domestication

The domestication of emmer wheat (Triticum turgidum spp. dicoccoides, genomes BBAA) was one of the key events during the emergence of agriculture in southwestern Asia, and was a prerequisite for the evolution of durum and common wheat. Single- and multilocus genotypes based on restriction fragment length polymorphism at 131 loci were analyzed to describe the structure of populations of wild and domesticated emmer and to generate a picture of emmer domestication and its subsequent diffusion across Asia, Europe and Africa. Wild emmer consists of two populations, southern and northern, each further subdivided. Domesticated emmer mirrors the geographic subdivision of wild emmer into the northern and southern populations and also shows an additional structure in both regions. Gene flow between wild and domesticated emmer occurred across the entire area of wild emmer distribution. Emmer was likely domesticated in the Diyarbakir region in southeastern Turkey, which was followed by subsequent hybridization and introgression from wild to domesticated emmer in southern Levant. A less likely scenario is that emmer was domesticated independently in the Diyarbakir region and southern Levant, and the Levantine genepool was absorbed into the genepool of domesticated emmer diffusing from southeastern Turkey. Durum wheat is closely related to domesticated emmer in the eastern Mediterranean and likely originated there. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Genetic Evidence of an East Asian Origin and Paleolithic Northward Migration of Y-chromosome Haplogroup N

The Y-chromosome haplogroup N-M231 (Hg N) is distributed widely in eastern and central Asia, Siberia, as well as in eastern and northern Europe. Previous studies suggested a counterclockwise prehistoric migration of Hg N from eastern Asia to eastern and northern Europe. However, the root of this Y chromosome lineage and its detailed dispersal pattern across eastern Asia are still unclear. We analyzed haplogroup profiles and phylogeographic patterns of 1,570 Hg N individuals from 20,826 males in 359 populations across Eurasia. We first genotyped 6,371 males from 169 populations in China and Cambodia, and generated data of 360 Hg N individuals, and then combined published data on 1,210 Hg N individuals from Japanese, Southeast Asian, Siberian, European and Central Asian populations. The results showed that the sub-haplogroups of Hg N have a distinct geographical distribution. The highest Y-STR diversity of the ancestral Hg N sub-haplogroups was observed in the southern part of mainland East Asia, and further phylogeographic analyses supports an origin of Hg N in southern China. Combined with previous data, we propose that the early northward dispersal of Hg N started from southern China about 21 thousand years ago (kya), expanding into northern China 12–18 kya, and reaching further north to Siberia about 12–14 kya before a population expansion and westward migration into Central Asia and eastern/northern Europe around 8.0–10.0 kya. This northward migration of Hg N likewise coincides with retreating ice sheets after the Last Glacial Maximum (22–18 kya) in mainland East Asia.     

东北亚地区野猪种群mtDNA遗传结构及系统地理发生

研究测定了中国东北、华北及四川西部72个野猪(Susscrofa)个体线粒体控制区全序列,并结合GenBank报道的日本野猪(S.s.leucomystax)、琉球野猪(S.s.riukiuanus)72个同源区序列,分析了东北亚地区野猪线粒体DNA的变异及系统地理格局。在东北亚地区野猪的线粒体控制区共发现42个变异位点,均为转换,共定义了34个单元型。单元型之间的系统发生分析表明,东北亚地区野猪来自同一祖先。东北亚地区野猪现生种群具有显著的种群遗传结构,其中日本野猪与分布于中国东北地区的东北野猪之间亲缘关系较近;而琉球野猪则与华北野猪间亲缘关系较近,与日本野猪和东北野猪间的关系相对较远。嵌套进化枝系统地理分析(Nestedcladephylogeographicalanalysis,NCPA)表明:东北亚地区野猪由同一祖先经过长距离的迁徙而形成现生各种群(或亚种);琉球野猪应起源于大陆野猪,其种群演化可能经历了片断化事件;华北野猪呈现南部种群遗传多样性高的特点,其种群内部曾经历了一次分布区由南向北的扩张