Excess of nonsynonymous polymorphism at Acph-1 in different gene arrangements of Drosophila subobscura

Nucleotide variation in the Acph-1 gene region was analyzed in a natural population of Drosophila subobscura from Bizerte (Tunisia). The lines studied differed in their gene arrangement for segment I of the O chromosome: 21 lines were O3+4+8, 21 were O3+4+23, and 3 were O3+4. According to chromosomal phylogenies, O3+4 is a central arrangement from which O3+4+8 and O3+4+23 originated. Strong genetic differentiation at Acph-1 was detected among the different arrangements, which is reflected in strong linkage disequilibrium between the variants at informative polymorphic sites and the type of arrangement. Estimates of silent nucleotide diversity are slightly lower within O3+4+23 (pisilent = 0.0166) than within O3+4+8 (pisilent = 0.0228) or O3+4 (pisilent = 0.0234). In contrast, nonsynonymous nucleotide diversity estimates (around 0.1%) are similar in the three arrangements. Most nonsynonymous rare variants are singletons, which results in highly significant Tajima's neutrality tests within the young O3+4+8 and O3+4+23 arrangements. This test is not significant for nonsynonymous mutations within a large Spanish O3+4 sample. In addition, a significant and marginally significant excess of nonsynonymous polymorphism was detected by the McDonald and Kreitman test within O3+4+23 and O3+4+8, respectively. This excess results in a rather high neutrality index (NI = 5.25) when both arrangements are jointly analyzed, in contrast to its value within the old O3+4 arrangement (NI = 1.74). The pattern of variation at Acph-1 within the young arrangements is unusual for nuclear genes and has the same characteristics previously detected in most genes of the mitochondrial genome. Assuming that most nonsynonymous mutations at Acph-1 are under weak negative selection, a smaller effective size of the young arrangements relative to O3+4 might explain the observed results. The relatively low frequency of O3+4+8 and O3+4+23 in the distribution area of D. subobscura, the more recent origin of these arrangements relative to O3+4 and the suppression of recombination in heterokaryotypes might contribute to the relatively small effective size of the young arrangements. Therefore, present results indicate that the differences in effective size and recombination caused by chromosomal arrangements are modulating nonsynonymous variation at Acph-1.     

A criterion for the establishment of a stable polymorphism of higher order with an application to the evolution of polymorphism

This note gives some further useful properties of the constant fitness selection model for multiple alleles which pertain to the effects of adding a new allele to n preexisting alleles in stable equilibrium. In particular the conditions are derived for the establishment of a stable equilibrium involving all n + 1 alleles. For 3 alleles (i.e. n = 2) I give a complete qualitative solution, including the case of the replacement of one diallelic polymorphism by another. As an application I discuss a possible mechanism for the evolution of polymorphism using Monte Carlo methods similar to Lewontin, Ginzburg and Tuljapurkar (1978).     

Polymorphism in a mangrove snail in Papua New Guinea

Snails in the genus Littorina (Gastropoda, Prosobranchia) were examined in an area of mangroves in Papua New Guinea. It is shown that these may be separated into three species belonging to the L. scabra complex. Two of the species live on the roots only while the third is restricted to the leaves. The root species are monomorphic and cryptic and co-exist with three other monomorphic cryptic species of snails. The leaf species is polymorphic. This is a particularly clear-cut case of the tendency seen in gastropods for species of dark, uniform habitats to be monomorphic, while those on bright, patterned foliage backgrounds are polymorphic. It is suggested that the polymorphism is maintained by resemblance of the morphs to different elements in the mangrove foliage background, which are present at rather constant frequencies over a wide area.     

Analysis of public single nucleotide polymorphisms in commercial pig populations

More than 5500 pig single nucleotide polymorphisms (SNPs) were recently identified and deposited in the public domain. To test the usefulness of these public SNPs, 109 SNPs were analysed for polymorphism within six commercial pig populations. A functional polymerase chain reaction (PCR) assay was obtained for 103 SNPs and it was possible to validate c. 59% by PCR-restriction fragment length polymorphism. Furthermore, polymorphism was found using a relatively limited number of genomic DNA samples, indicating that these polymorphisms are segregating at a useful frequency in these populations. The high percentage of validated markers demonstrates the utility of these public pig SNPs to identify loci responsible for economically important traits in commercial pig populations.     

Genetic characterization of Gainj- and Kalam-speaking peoples of Papua New Guinea

The research presented focuses on genetic variation in the Gainj- and Kalam-speaking peoples of highland Papua New Guinea. The primary data are typings at 51 genetic loci observed on 600 individuals who reside in 21 census units, called parishes. These data are augmented by cultural and demographic information that has also been collected. Parish sizes are small, ranging from 20 to about 200 individuals. Direct Western contact with these people has been occurring only for the past three decades. Although Westernization is currently increasing, we find that much of the traditional settlement pattern and mate exchange system is preserved. There are segregating variants at 27 loci. Four rare variants are initially described: NP 4-Kalam, ADA 6-Kalam, PEPA 3-Kalam, and FUM 2-Kalam. We find evidence for a new Gm haplotype, a;-, that is recessive to all other Gm haplotypes. It occurs at a high enough frequency, f(a;-) = 0.119, to be considered a "private polymorphism." Average per locus heterozygosity is estimated to be 0.053. This value is not statistically different from levels observed on two modern urban populations. Thus, there is no evidence for a reduced level of genetic variation in these people, despite small parish sizes and a relatively unacculturated social structure.     

Evaluation of 16 loci to examine the cross‐species utility of single nucleotide polymorphism arrays

Large collections of single nucleotide polymorphisms (SNPs) have recently been identified from a number of livestock genomes. This raises the possibility that SNP arrays might be useful for analysis in related species for which few genetic markers are currently available. To address the likely success of such an approach, the aim of this study was to examine the threshold number and position of flanking mutations which act to prevent genotype calls being produced. Sequence diversity was measured across 16 loci containing SNPs known either to work successfully between species or fail between species. In pairwise comparisons between domestic and wild sheep, sequence divergence surrounding working SNP assays was significantly lower than that surrounding non‐functional assays. In addition, the location of flanking mismatches tended to be closer to the target SNP in loci that failed to generate genotype calls across species. The magnitude of sequence divergence observed for both working and non‐functional assays was compared with the divergence separating domestic sheep from European Mouflon, African Barbary, goat and cattle. The results suggest that the utility of SNP arrays for analysis of shared polymorphism will be restricted to closely related pairs of species. Analysis across more divergent species will, however, be successful for other objectives, such as the identification of the ancestral state of SNPs.     

How fish-helminth associations arise: an example from Arctic charr in Loch Rannoch

Three sympatric morphs of Arctic charr Salvelinus alpinus occur in Loch Rannoch, Scotland, and are identified by their differing head morphology and diet. These are small-headed benthic, large-headed benthic and pelagic morphs. Six species of endoparasitic helminth were found in the fish, but the morphs had different patterns of infection. Overall infections in pelagic charr were heavier than in large-headed benthics, which were in turn heavier than in small-headed benthics, even though benthic charr live longer than pelagics. Pelagic fish had high prevalences and intensities of pseudophyllidean tapeworms, the intermediate hosts of which are copepods. The prevalence and intensity of metacercariae of Diplostomum sp. (the intermediate hosts of which are snails) were high in the benthic morphs. The results are discussed in terms of the effects of ecological factors on transmission of helminth parasites to their hosts and the evolution of host-parasite associations.     

Acetylation polymorphism and leprosy

The sulfones are the drug of choice in the treatment of leprosy, with dapsone as the clear favorite. The major route for dapsone metabolism leading to its inactivation and excretion is via acetylation by hepaticN-acetyl transferase (NAT), as is the case with isoniazid (INH) and sulfamethazine (SMZ). The enzyme is known to exhibit genetic polymorphism. The object of the present study is mainly to determine the incidence of acetylator phenotype in a population of leprosy patients with a view to evaluating the degree of association, if any, between phenotype and the disease. Obviously a knowledge of the incidence of the phenotypes may provide a valuable contribution to the institution of more rational and successful therapy. In the normal or control subjects, as well as in the leprosy patients, the frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum samples are bimodal, and this indicates the existence of a genetic polymorphism. Based on the bimodality, individuals were classified as either rapid or slow acetylators, and the incidence of the slow acetylator phenotype of about 51% was observed in the leprosy population. This gives a relatively high incidence of the allele controlling the slow acetylator (q=0.73). Although there is evidence that the mean percentage of SMZ acetylated in leprosy patients of the slow acetylator phenotype is significantly higher than that observed for the same phenotype in the controls (t=4.86,P<0.02), statistical analyses show that there is no association between the slow acetylator phenotype and the disease. Most of the individuals in the slow acetylator phenotype tend to show some adverse reactions when a total weekly dose of 600 mg is given. Such adverse reactions include heightened lepra reactions, blurring of vision, and headache. These reactions, we think, are due to accumulation of the drug in the subjects. This therefore brings into sharp focus the desirability of knowing the acetylator phenotype of an individual before the initiation of dapsone therapy.     

Using SD-AFLP and MSAP to assess CCGG methylation in the banana genome

Two amplified fragment length polymorphism (AFLP)-derived techniques were used to assess methylation at CCGG sites in the banana genome. Assessment of these techniques revealed that, while amplification steps are very reproducible, the ligation step is more subject to variability. Overall, these techniques produced an error rate of 0.2% per analysed band. Statistical approach highlights the fact that sample duplication is necessary to produce reliable results. This study involved 18 primer pairs and found that in the banana genome, roughly 80% of CCGG sites are unmethylated, 5% are methylated at the internal cytosine, and 15% are methylated at the external or both cytosines.     

双孢蘑菇及大肥菇的种内及种间多态性RAPD分析*

应用RAPD方法分析双孢蘑菇（Agaricusbisporus）及大肥菇（Agaricusbitorquis）的种内及种间多态性,进一步证实由于双孢蘑菇的遗传保守性,多数孢子为自体可育的异核孢子,从而导致种内相似性很高;而依赖天然杂交具四孢特性的大肥菇种内相似程度较低。研究还分析评价了蘑菇属中的这两个不同种之间的亲缘关系,为种间杂交选材提供了理论依据。     

双孢蘑菇及大肥菇的种内及种间多态性RAPD分析

应用RAPD方法分析双孢蘑菇（Agaricusbisporus）及大肥菇（Agaricusbitorquis）的种内及种间多态性,进一步证实由于双孢蘑菇的遗传保守性,多数孢子为自体可育的异核孢子,从而导致种内相似性很高;而依赖天然杂交具四孢特性的大肥菇种内相似程度较低。研究还分析评价了蘑菇属中的这两个不同种之间的亲缘关系,为种间杂交选材提供了理论依据。     

Polymorphism at the Hor 1 locus of barley (Hordeum vulgare L.)

The Hor 1 locus of barley encodes a group of seed storage polypeptides called C hordein. Two-dimensional electrophoretic analysis of C-hordein fractions from six cultivars with different alleles at the Hor 1 locus showed extensive polymorphism. A total of 34 major polypeptides was mapped, with between 4 and 18 present in each cultivar. There was less variation among the same cultivars in the numbers (6 to 10) of restriction fragments of genomic DNA which hybridized to a cDNA clone related to C hordein. The total number of restriction fragments was also lower (22), and most pairs of cultivars had more restriction fragments than polypeptides in common. A total number of about 20–30 C-hordein genes per haploid genome was estimated. The results indicate that cultivars differ mainly in the extent of gene and polypeptide divergence, rather than in the degree of gene reiteration. They are consistent with the proposed origin of the multiple structural genes at the Hor 1 locus by the duplication and divergence of a single ancestral gene.NACB was supported by a grant from the Home Grown Cereals Authority.     

DNA from Buccal Swabs Suitable for High-Throughput SNP Multiplex Analysis

We sought a convenient and reliable method for collection of genetic material that is inexpensive and noninvasive and suitable for self-collection and mailing and a compatible, commercial DNA extraction protocol to meet quantitative and qualitative requirements for high-throughput single nucleotide polymorphism (SNP) multiplex analysis on an automated platform. Buccal swabs were collected from 34 individuals as part of a pilot study to test commercially available buccal swabs and DNA extraction kits. DNA was quantified on a spectrofluorometer with Picogreen dsDNA prior to testing the DNA integrity with predesigned SNP multiplex assays. Based on the pilot study results, the Catch-All swabs and Isohelix buccal DNA isolation kit were selected for our high-throughput application and extended to a further 1140 samples as part of a large cohort study. The average DNA yield in the pilot study (n=34) was 1.94 μg ± 0.54 with a 94% genotyping pass rate. For the high-throughput application (n=1140), the average DNA yield was 2.44 μg ± 1.74 with a ≥93% genotyping pass rate. The Catch-All buccal swabs are a convenient and cost-effective alternative to blood sampling. Combined with the Isohelix buccal DNA isolation kit, they provided DNA of sufficient quantity and quality for high-throughput SNP multiplex analysis.     

Heating properties of morphs of the mangrove snail Littoraria pallescens

The rate of heating and the temperature attained after 10 and 20 min have been examined for shells of the yellow, dark and orange morphs of the mangrove leaf snail Littoraria pallescens. Under the experimental conditions used, heating from 20 to 40C took 5–10 min and thereafter the temperature remained roughly constant for up to 20 min. This represents temperature conditions which the animals are likely to experience in the wild. Large shells heat more slowly than small ones and reach lower temperatures. At around 40C yellows are on average 1.5C cooler than the dark morph, and orange individuals lie between. This difference could account for the observed difference between morphs in their choice of preferred leaf surface. Besides differing in colour, yellows are thinner and less heavy than dark shells, which probably contributes to the fact that they arc less robust.     

Heterozygote advantage fails to explain the high degree of polymorphism of the MHC

Major histocompatibility (MHC) molecules are encoded by extremely polymorphic genes and play a crucial role in vertebrate immunity. Natural selection favors MHC heterozygous hosts because individuals heterozygous at the MHC can present a larger diversity of peptides from infectious pathogens than homozygous individuals. Whether or not heterozygote advantage is sufficient to account for a high degree of polymorphism is controversial, however. Using mathematical models we studied the degree of MHC polymorphism arising when heterozygote advantage is the only selection pressure. We argue that existing models are misleading in that the fitness of heterozygotes is not related to the MHC alleles they harbor. To correct for this, we have developed novel models in which the genotypic fitness of a host directly reflects the fitness contributions of its MHC alleles. The mathematical analysis suggests that a high degree of polymorphism can only be accounted for if the different MHC alleles confer unrealistically similar fitnesses. This conclusion was confirmed by stochastic simulations, including mutation, genetic drift, and a finite population size. Heterozygote advantage on its own is insufficient to explain the high population diversity of the MHC.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

HLA-F研究进展

人类白细胞抗原（human leucocyte antigen,HLA）复合体是人体中基因多态性最高的基因复合体,其多态性与疾病遗传易感性显著相关。人类白细胞抗原-F（human leucocyte antigen-F,HLA-F）属于非经典HLA I类分子中的一员,与HLA-E、-G在结构上十分相似,具有有限的多态性。近年来多数学者聚焦于HLA-F基因转录及分子表达调控、HLA-F表达与临床相关性及HLA-F抗体研制,且取得了重要成果。就HLA-F的研究进展作一综述。     

神经管畸形相关基因的研究进展

神经管畸形是由遗传和环境因素共同作用而导致的一种常见的出生缺陷。遗传因素中包括细胞增殖因子、转录因子及影响叶酸代谢的关键酶的基因。本文着重从动物模型和群体流行病学调查两方面,简述目前研究的热点基因及特定位点的遗传多态性与神经管畸形的关系,从而揭示多因素作用在神经管畸形病因学研究中的意义。 Progress in Researches on Neural Tube Defects Related the Genes QU Mei,LI Zhu Institute of Reproductive and Child Health of Peking University,National Reference Laboratory on Reproductive Health Research Ministry of Health,Beijing 100083,China Abstract:Neural tube defects are common birth defects which are ascribed to the combination of genetic and environmental factors.The genetic factors include cell growth factors,transformation factors and key enzymic genes involved in folate metabolism.This paper reviews the genes as focus of current investigantion and the relationship between the genetic polymorphism on the specific sites and neural tube defects based on animal model and population epidemiological study.It indicats that the multifactors play an important role in the etiology of neural tube defects. Key words：neural tube defects; genetic polymorphism     

26个唐菖蒲品种RAPD分析

唐菖蒲是世界著名的切花之一,由于是纯粹的外来品种,目前国际上对其分类尚无统一的方法,主要是依据其生物习性等形态特征进行分类,受环境影响很大。同工酶是基因的产物,利用同工酶可以进行唐菖蒲品种鉴定和分类,但它在植物的不同器官组织发育的不同时期存在差异,而分子标记技术具有不受环境、器官、组织发育不同时期影响、遗传性稳定、分析简单等特点而被广泛应用在花卉品种分类上。利用RAPD技术对26个主要唐菖蒲切花品种进行分类和亲缘关系的研究,从520个随机引物中筛选出33个用于PCR反应,共在206个位点上扩增出条带,平均每个引物扩增位点6.24个,多态性位点185个,占总带数的89.8%,可以进行品种的鉴定。从分子水平揭示出唐菖蒲切花品种种质资源遗传基础狭窄,夏花大花型唐菖蒲品种间存在一定的亲缘关系。     

A suite of molecular markers for identifying species, detecting introgression and describing population structure in spadefoot toads (Spea spp.)

Two congeneric species of spadefoot toad, Spea multiplicata and Spea bombifrons, have been the focus of hybridization studies since the 1970s. Because complex hybrids are not readily distinguished phenotypically, genetic markers are needed to identify introgressed individuals. We therefore developed a set of molecular markers (amplified fragment length polymorphism, polymerase chain reaction-restriction fragment length polymorphism and single nucleotide polymorphism) for identifying pure-species, F1 hybrids and more complex introgressed types. To do so, we tested a series of markers across both species and known hybrids using populations in both allopatry and sympatry. We retained those markers that differentiated the two pure-species and also consistently identified known species hybrids. These markers are well suited for identifying hybrids between these species. Moreover, those markers that show variation within each species can be used in conjunction with existing molecular markers in studies of population structure and gene flow.