Identification of three feline immunodeficiency virus (FIV) env gene subtypes and comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns.

Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like illnesses in cats. As such, FIV appears to be a feline analog of human immunodeficiency virus (HIV). A hallmark of HIV infection is the large degree of viral genetic diversity that can develop within an infected individual and the even greater and continually increasing level of diversity among virus isolates from different individuals. Our goal in this study was to determine patterns of FIV genetic diversity by focusing on a 684-nucleotide region encompassing variable regions V3, V4, and V5 of the FIV env gene in order to establish parallels and distinctions between FIV and HIV type 1 (HIV-1). Our data demonstrate that, like HIV-1, FIV can be separated into distinct envelope sequence subtypes (three are described here). Similar to that found for HIV-1, the pairwise sequence divergence within an FIV subtype ranged from 2.5 to 15.0%, whereas that between subtypes ranged from 17.8 to 26.2%. However, the high number of synonymous nucleotide changes among FIV V3 to V5 env sequences may also include a significant number of back mutations and suggests that the evolutionary distances among FIV subtypes are underestimated. Although only a few subtype B viruses were available for examination, the pattern of diversity between the FIV A and B subtypes was found to be significantly distinct; subtype B sequences had proportionally fewer mutations that changed amino acids, compared with silent changes, suggesting a more advanced state of adaptation to the host. No similar distinction was evident for HIV-1 subtypes. The diversity of FIV genomes within individual infected cats was found to be as high as 3.7% yet twofold lower than that within HIV-1-infected people over a comparable region of the env gene. Despite these differences, significant parallels between patterns of FIV evolution and HIV-1 evolution exist, indicating that a wide array of potentially divergent virus challenges need to be considered in FIV vaccine and pathogenesis studies.     

Basic properties of populations generated in the frame of one-parameter discrete model of genetic diversity

Previously, when discussing the properties of one parameter discrete model of genetic diversity (M.Yu. Shchelkanov et al, J. Biomol. Struct. Dyn. 15, 887-894 (1998)), we took into account Hamming distance distribution only between precursor and arbitrary descendant sequences. However, really there are sets of sequence populations produced during amplification process. In the presented work we have investigated Hamming distance distributions between sequences from different descendant sets produced in the frame of one parameter discrete model. Two basic descendant generation operators (so called amplifiers) are introduced: 1) the last generation amplifier, L, which produces descendants with precursor elimination; 2) all generations amplifier, G, which produces descendants without precursor elimination. Generalization of one-parameter discrete model for the case when precursor sequences do not coincide are carried out. Using this generalization we investigate the distribution of Hamming distances between L- and G-generated sequences. Basic properties of L and G operators, L/G-choice alternative problem have been discussed. Obtained results have common theoretical significance, but they are more suitable for high level genetic diversity process (for example, HIV diversity).     

Dependencies of Substitution Steps Number on Hamming Distance Are Identical For One-parameter Discrete Models of Both Direct and Parallel Genetic Diversity

Abstract

With the help of previously introduced enumeration procedure (M.Yu. Shchelkanov, A.N. Yudin, A.V Antonov, N.S. Starikov, A.A. Vedenov, E.V. Karamov, J. Biomol. Struct. Dyn. 15, 217–229 (1997)) and probability distribution function for the enumeration after some substitution steps (M.Yu. Shchelkanov, L.A. Soinov, V.V. Zalunin, D.A. Gumennyi, A.N. Yudin, A.A. Natan, V.B. Kireev, E.V. Karamov, J. Biomol. Struct. Dyn. 15, N 4, (1998)) we have demonstrated that dependencies of replication acts number on Hamming distance are identical for one-parameter discrete models of both direct and parallel genetic diversity.     

Individual-and population-based diversity in restriction-modification systems

Restriction-modification (RM) systems are cognate gene complexes that code for an endonuclease and a methylase. They are often thought to have developed in bacteria as protection against invading genetic material, e.g., phage DNA. The high diversity of RM systems, as observed in nature, is often ascribed to the coevolution of RM systems (which ‘invent’ novel types) and phages. However, the extent to which phages are insensitive to RM systems casts doubts on the effectiveness of RM systems as protection against infection and thereby on the reason for the diversity of RM systems. We present an eco-evolutionary model in order to study the evolution of the diversity of RM systems. The model predicts that in general diversity of RM systems is high. More importantly, the diversity of the RM systems is expressed either at the individual level or at the population level. In the first case all individuals carry RM systems of all sequence specificities, whereas in the second case they carry only one RM system or no RM systems at all. Nevertheless, in the second case the same number of sequence specificities are present in the population.     

Molecular evolution at Mhc genes in two populations of chinook salmon Oncorhynchus tshawytscha

The DNA sequences of four exons of the MHC (major histocompatibilty complex) were examined in chinook salmon ( Oncorhynchus tshawytscha ) from an interior (Nechako River) and a coastal (Harrison River) population in the Fraser River drainage of British Columbia. Mhc class I A1, A2 and A3 sequences and a class II B1 sequence were obtained by PCR from each of 16–20 salmon from each population. The class I A1 and a pair of linked A2–A3 exons were derived from two different classical salmonid class I genes, Sasa-A and Onmy-UA , respectively. Allelic variation for B1, A1 and A2 was characterized by the high levels of nonsynonymous substitution indicative of the effects of natural selection on Mhc domains that contain peptide binding regions. The number of alleles detected at each of the four exons ranged from three ( B1 ) to 22 ( A1 ), but levels of nucleotide sequence divergence at all four exons were low relative to classical mammalian Mhc genes. The nucleotide similarity among alleles ranged between 89 and 99% over all exons, and all four domains possessed only two major sequence motifs. Allelic distributions at B1, A1 and A3 confirmed the genetic distinctiveness of the Harrison and Nechako chinook salmon populations revealed in previous studies. The two major allelic motifs of B1 and A1 segregated strongly between the populations. In spite of evidence that allelic diversity at these chinook salmon Mhc exons has been generated by selection, the level and distribution of diversity in the two salmon populations strongly reflected the demographic history of the species, which has been characterized by repeated bottlenecks and isolation-by-distance in glacial refugia.     

具混合繁殖策略的草本植物异果舞花姜的居群遗传结构

 居群遗传结构的形成受到各种因素的影响。其中, 繁殖方式可能对居群内遗传变异有极其重要的意义, 而距离隔离也是居群间变异产 生的主要原因之一。异果舞花姜(Globba racemosa)具有混合繁殖策略(以种子进行有性繁殖和以珠芽进行无性克隆繁殖)。调查分布于云南的7 个异果舞花姜居群间有性与无性克隆繁殖的差异。采用ISSR标记研究各个居群的遗传多样性与克隆多样性, 探讨繁殖方式和距离隔离对居群遗 传结构的影响。调查结果表明, 异果舞花姜各个居群存在一定的繁殖差异。ISSR结果显示, 该种在种水平上呈现较高水平的遗传变异 (PPB=71.19%), 大部分的变异来自于居群间(G_ST = 0.590 7)。同时, 异果舞花姜具有较高水平克隆多样性(G/N = 0.88)。遗传多样性和克隆多 样性与繁殖水平的变异间相关性不明显, 说明繁殖方式不是居群遗传结构形成的必要和决定性的因素。居群间的地理距离与遗传距离显著相关 (r = 0.68, p < 0.05), 表明距离隔离是居群间遗传变异形成的重要原因。其它因素(如少量新有性个体的补充、细胞突变、奠基效应等)也对 异果舞花姜居群遗传结构的形成和维持起到了重要作用。     

Impact of genetic architecture on the relative rates of X versus autosomal adaptive substitution

Molecular evolutionary theory predicts that the ratio of autosomal to X-linked adaptive substitution (K(A)/K(x)) is primarily determined by the average dominance coefficient of beneficial mutations. Although this theory has profoundly influenced analysis and interpretation of comparative genomic data, its predictions are based upon two unverified assumptions about the genetic basis of adaptation. The theory assumes that 1) the rate of adaptively driven molecular evolution is limited by the availability of beneficial mutations, and 2) the scaling of evolutionary parameters between the X and the autosomes (e.g., the beneficial mutation rate, and the fitness effect distribution of beneficial alleles, per X-linked versus autosomal locus) is constant across molecular evolutionary timescales. Here, we show that the genetic architecture underlying bouts of adaptive substitution can influence both assumptions, and consequently, the theoretical relationship between K(A)/K(x) and mean dominance. Quantitative predictions of prior theory apply when 1) many genomically dispersed genes potentially contribute beneficial substitutions during individual steps of adaptive walks, and 2) the population beneficial mutation rate, summed across the set of potentially contributing genes, is sufficiently small to ensure that adaptive substitutions are drawn from new mutations rather than standing genetic variation. Current research into the genetic basis of adaptation suggests that both assumptions are plausibly violated. We find that the qualitative positive relationship between mean dominance and K(A)/K(x) is relatively robust to the specific conditions underlying adaptive substitution, yet the quantitative relationship between dominance and K(A)/K(x) is quite flexible and context dependent. This flexibility may partially account for the puzzlingly variable X versus autosome substitution patterns reported in the empirical evolutionary genomics literature. The new theory unites the previously separate analysis of adaptation using new mutations versus standing genetic variation and makes several useful predictions about the interaction between genetic architecture, evolutionary genetic constraints, and effective population size in determining the ratio of adaptive substitution between autosomal and X-linked genes.     

Discrete and continuous mathematical models of DNA branch migration

DNA junctions, known as Holliday junctions, are intermediates in genetic recombination between DNAs. In this structure, two double-stranded DNA helices with similar sequence are joined at a branch point. The branch point can move along these helices when strands with the same sequence are exchanged. Such branch migration is modeled as a random walk. First, we model this process discretely, such that the motion of the branch is represented as transfer between discrete compartments. This is useful in analysing the results of DNA branch migration on junction comprised of synthetic oligonucleotides. The limit in which larger numbers of smaller steps go to continuous motion of the branch is also considered. We show that the behavior of the continuous system is very similar to that of the discrete system when there are more than just a few compartments. Thus, even branch migration on oligonucleotides can be viewed as a continuous process. One consequence of this is that a step size must be assumed when determining rate constants of branch migration.We compare migration where forward and backward movements of the branch are equally probable to biased migration where one direction is favored over the other. In the latter case larger differences between the discrete and continuous cases are predicted, but the differences are still small relative to the experimental error associated with experiments to measure branch migration in oligonucleotides.     

DnaSAM: Software to perform neutrality testing for large datasets with complex null models

Patterns of DNA sequence polymorphisms can be used to understand the processes of demography and adaptation within natural populations. High-throughput generation of DNA sequence data has historically been the bottleneck with respect to data processing and experimental inference. Advances in marker technologies have largely solved this problem. Currently, the limiting step is computational, with most molecular population genetic software allowing a gene-by-gene analysis through a graphical user interface. An easy-to-use analysis program that allows both high-throughput processing of multiple sequence alignments along with the flexibility to simulate data under complex demographic scenarios is currently lacking. We introduce a new program, named DnaSAM, which allows high-throughput estimation of DNA sequence diversity and neutrality statistics from experimental data along with the ability to test those statistics via Monte Carlo coalescent simulations. These simulations are conducted using the ms program, which is able to incorporate several genetic parameters (e.g. recombination) and demographic scenarios (e.g. population bottlenecks). The output is a set of diversity and neutrality statistics with associated probability values under a user-specified null model that are stored in easy to manipulate text file.     

Inferring complex DNA substitution processes on phylogenies using uniformization and data augmentation

A new method is developed for calculating sequence substitution probabilities using Markov chain Monte Carlo (MCMC) methods. The basic strategy is to use uniformization to transform the original continuous time Markov process into a Poisson substitution process and a discrete Markov chain of state transitions. An efficient MCMC algorithm for evaluating substitution probabilities by this approach using a continuous gamma distribution to model site-specific rates is outlined. The method is applied to the problem of inferring branch lengths and site-specific rates from nucleotide sequences under a general time-reversible (GTR) model and a computer program BYPASSR is developed. Simulations are used to examine the performance of the new program relative to an existing program BASEML that uses a discrete approximation for the gamma distributed prior on site-specific rates. It is found that BASEML and BYPASSR are in close agreement when inferring branch lengths, regardless of the number of rate categories used, but that BASEML tends to underestimate high site-specific substitution rates, and to overestimate intermediate rates, when fewer than 50 rate categories are used. Rate estimates obtained using BASEML agree more closely with those of BYPASSR as the number of rate categories increases. Analyses of the posterior distributions of site-specific rates from BYPASSR suggest that a large number of taxa are needed to obtain precise estimates of site-specific rates, especially when rates are very high or very low. The method is applied to analyze 45 sequences of the alpha 2B adrenergic receptor gene (A2AB) from a sample of eutherian taxa. In general, the pattern expected for regions under negative selection is observed with third codon positions having the highest inferred rates, followed by first codon positions and with second codon positions having the lowest inferred rates. Several sites show exceptionally high substitution rates at second codon positions that may represent the effects of positive selection.     

Drawing ecological inferences from coincident patterns of population‐ and community‐level biodiversity

Biodiversity is comprised of genetic and phenotypic variation among individual organisms, which might belong to the same species or to different species. Spatial patterns of biodiversity are of central interest in ecology and evolution for several reasons: to identify general patterns in nature (e.g. species–area relationships, latitudinal gradients), to inform conservation priorities (e.g. identifying hotspots, prioritizing management efforts) and to draw inferences about processes, historical or otherwise (e.g. adaptation, the centre of origin of particular clades). There are long traditions in ecology and evolutionary biology of examining spatial patterns of biodiversity among species (i.e. in multispecies communities) and within species, respectively, and there has been a recent surge of interest in studying these two types of pattern simultaneously. The idea is that examining both levels of diversity can materially advance the above‐stated goals and perhaps lead to entirely novel lines of inquiry. Here, we review two broad categories of approach to merging studies of inter‐ and intraspecific variation: (i) the study of phenotypic trait variation along environmental gradients and (ii) the study of relationships between patterns of molecular genetic variation within species and patterns of distribution and diversity across species. For the latter, we report a new meta‐analysis in which we find that correlations between species diversity and genetic diversity are generally positive and significantly stronger in studies with discrete sampling units (e.g. islands, lakes, forest fragments) than in studies with nondiscrete sampling units (e.g. equal‐area study plots). For each topic, we summarize the current state of knowledge and key future directions.     

Microsatellite diversity associated with ecological factors in Hordeum spontaneum populations in Israel

Microsatellite diversity at 18 loci was analysed in 94 individual plants of 10 wild barley, Hordeum spontaneum (C. Koch) Thell., populations sampled from Israel across a southward transect of increasing aridity. Allelic distribution in populations was not distributed randomly. Estimates of mean gene diversity were highest in stressful arid-hot environments. Sixty-four per cent of the genetic variation was partitioned within populations and 36% between populations. Associations between ecogeographical variables and gene diversity, H(e), were established in nine microsatellite loci. By employing principle component analysis we reduced the number of ecogeographical variables to three principal components including water factors, temperature and geography. At three loci, stepwise multiple regression analysis explained significantly the gene diversity by a single principal component (water factors). Based on these observations it is suggested that simple sequence repeats are not necessarily biologically neutral.     

Out of Anatolia: longitudinal gradients in genetic diversity support an eastern origin for a circum-Mediterranean oak gallwasp Andricus quercustozae

Many studies have addressed the latitudinal gradients in intraspecific genetic diversity of European taxa generated during postglacial range expansion from southern refugia. Although Asia Minor is known to be a centre of diversity for many taxa, relatively few studies have considered its potential role as a Pleistocene refugium or a potential source for more ancient westward range expansion into Europe. Here we address these issues for an oak gallwasp, Andricus quercustozae (Hymenoptera: Cynipidae), whose distribution extends from Morocco along the northern coast of the Mediterranean through Turkey to Iran. We use sequence data for a fragment of the mitochondrial gene cytochrome b and allele frequency data for 12 polymorphic allozyme loci to answer the following questions: (1) which regions represent current centres of genetic diversity for A. quercustozae? Do eastern populations represent one refuge or several discrete glacial refugia? (2) Can we infer the timescale and sequence of the colonization processes linking current centres of diversity? Our results suggest that A. quercustozae was present in five distinct refugia (Iberia, Italy, the Balkans, southwestern Turkey and northeastern Turkey) with recent genetic exchange between Italy and Hungary. Genetic diversity is greatest in the Turkish refugia, suggesting that European populations are either (a) derived from Asia Minor, or (b) subject to more frequent population bottlenecks. Although Iberian populations show the lowest diversity for putatively selectively neutral markers, they have colonized a new oak host and represent a genetically and biologically discrete entity within the species.     

Likelihood analysis of phylogenetic networks using directed graphical models

A method for computing the likelihood of a set of sequences assuming a phylogenetic network as an evolutionary hypothesis is presented. The approach applies directed graphical models to sequence evolution on networks and is a natural generalization of earlier work by Felsenstein on evolutionary trees, including it as a special case. The likelihood computation involves several steps. First, the phylogenetic network is rooted to form a directed acyclic graph (DAG). Then, applying standard models for nucleotide/amino acid substitution, the DAG is converted into a Bayesian network from which the joint probability distribution involving all nodes of the network can be directly read. The joint probability is explicitly dependent on branch lengths and on recombination parameters (prior probability of a parent sequence). The likelihood of the data assuming no knowledge of hidden nodes is obtained by marginalization, i.e., by summing over all combinations of unknown states. As the number of terms increases exponentially with the number of hidden nodes, a Markov chain Monte Carlo procedure (Gibbs sampling) is used to accurately approximate the likelihood by summing over the most important states only. Investigating a human T-cell lymphotropic virus (HTLV) data set and optimizing both branch lengths and recombination parameters, we find that the likelihood of a corresponding phylogenetic network outperforms a set of competing evolutionary trees. In general, except for the case of a tree, the likelihood of a network will be dependent on the choice of the root, even if a reversible model of substitution is applied. Thus, the method also provides a way in which to root a phylogenetic network by choosing a node that produces a most likely network.     

Stochastic search variable selection based on two mixture components and continuous‐scale weighting

Stochastic search variable selection (SSVS) is a Bayesian variable selection method that employs covariate‐specific discrete indicator variables to select which covariates (e.g., molecular markers) are included in or excluded from the model. We present a new variant of SSVS where, instead of discrete indicator variables, we use continuous‐scale weighting variables (which take also values between zero and one) to select covariates into the model. The improved model performance is shown and compared to standard SSVS using simulated and real quantitative trait locus mapping datasets. The decision making to decide phenotype‐genotype associations in our SSVS variant is based on median of posterior distribution or using Bayes factors. We also show here that by using continuous‐scale weighting variables it is possible to improve mixing properties of Markov chain Monte Carlo sampling substantially compared to standard SSVS. Also, the separation of association signals and nonsignals (control of noise level) seems to be more efficient compared to the standard SSVS. Thus, the novel method provides efficient new framework for SSVS analysis that additionally provides whole posterior distribution for pseudo‐indicators which means more information and may help in decision making.     

Assessing genetic diversity of wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.) germplasm using microsatellite markers

A set of 24 wheat microsatellite markers, representing at least one marker from each chromosome, was used for the assessment of genetic diversity in 998 accessions of hexaploid bread wheat (Triticum aestivum L.) which originated from 68 countries of five continents. A total of 470 alleles were detected with an average allele number of 18.1 per locus. The highest number of alleles per locus was detected in the B genome with 19.9, compared to 17.4 and 16.5 for genomes A and D, respectively. The lowest allele number per locus among the seven homoeologous groups was observed in group 4. Greater genetic variation exists in the non-centromeric regions than in the centromeric regions of chromosomes. Allele numbers increased with the repeat number of the microsatellites used and their relative distance from the centromere, and was not dependent on the motif of microsatellites. Gene diversity was correlated with the number of alleles. Gene diversity according to Nei for the 26 microsatellite loci varied from 0.43 to 0.94 with an average of 0.77, and was 0.78, 0.81 and 0.73 for three genomes A, B and D, respectively. Alleles for each locus were present in regular two or three base-pair steps, indicating that the genetic variation during the wheat evolution occurred step by step in a continuous manner. In most cases, allele frequencies showed a normal distribution. Comparative analysis of microsatellite diversity among the eight geographical regions revealed that the accessions from the Near East and the Middle East exhibited more genetic diversity than those from the other regions. Greater diversity was found in Southeast Europe than in North and Southwest Europe. The present study also indicates that microsatellite markers permit the fast and high throughput fingerprinting of large numbers of accessions from a germplasm collection in order to assess genetic diversity.     

Genetic diversity in exotic oat germplasm & resistance against barley yellow dwarf virus

Oat (Avena sativa L.) is an important fodder crop of Pakistan, though with low productivity. The present study was conducted to evaluate the performance and genetic diversity of exotic oat germplasm, with emphasis on cereal yellow dwarf virus resistance. A total of 16 exotic line (introduced from Aarhus University Denmark) and 1 local line (provided by The University of Agriculture Peshawar), were grown during the season 2017–18 in Completely Randomized Block Design with three replications across two locations of Khyber Pakhtunkhwa i.e., Peshawar and Kohat. Field testing enabled to collect the data on BYDV incidence, BYDV severity, aphid infestation, plant height, leaf area, panicle length, panicle weight, spikelets per panicle, 1000 grain weight (g), grain yield (g), biological yield (g) and harvest index (%). Prevalence of BYDV was variable across location and over time. Six weeks data showed high disease pressure at Peshawar (85%), with SA-O-01 genotype having AUDPC value of 95%. Almost all the varieties showed less tolerance towards the Aphids attack. Line SA-O-15 showed the maximum 1000 grain weight (42.6 g) at Kohat, while SA-O-4 showed the maximum 1000 grain weight (60.7 g) at Peshawar. Line SA-O-05 (3634 g per (0.9 m²) plot) gave the maximum biological yield at Kohat station, while Line SA-O-01 gave the maximum biological yield (2517 g) at Peshawar. Mean grain yield for Kohat was recorded 0.155 g per (0.9 m²) plot while for Peshawar it was 0.231 g per (0.9 m²) plot. At Kohat line SA-O-10 produced the maximum grain yield (0.229 g), while line SA-O-12 produced the maximum grain yield at Peshawar (0.288 g). Molecular genotyping with a set of 4 RAPD primers revealed substantial diversity among17 oat lines. A total of 23 loci were amplified showing a high level of variations and polymorphism among the proposed lines. The maximum number of loci was recorded for GLA-04 (8), while the minimum number of loci was recorded for GLD-18 (4). Among the tested RAPD primers the maximum gene diversity (0.529) was recorded for loci GLA-03B230, GLA-04B130, GLA-04B300, GLB-05B150 and GLA-18B100 while the minimum (0.118) genetic diversity was recorded for loci GLA-03B600, GLB-05B330 and GLA-18B500. A clear divergence was found between most of the exotic oat lines. The observed genetic diversity in exotic oat germplasm and its resistance towards Barley Yellow Dwarf virus could be useful for oat genetic improvement and broadening the genetic background of cultivated oat germplasm.     

The effect of biodiversity on tree productivity: from temperate to boreal forests

Aim An important issue regarding biodiversity concerns its influence on ecosystem functioning. Experimental work has led to the proposal of mechanisms such as niche complementarity. However, few attempts have been made to confirm these in natural systems, especially in forests. Furthermore, one of the most interesting unresolved questions is whether the effects of complementarity on ecosystem functioning (EF) decrease in favour of competitive exclusions over an increasing productivity gradient. Using records from permanent forest plots, we asked the following questions. (1) Is tree productivity positively related to diversity? (2) Does the effect of diversity increase in less productive forests? (3) What metric of diversity (e.g. functional or phylogenetic diversity) better relates to tree productivity? Location Temperate, mixed and boreal forests of eastern Canada. Methods Over 12,000 permanent forest plots, from temperate to boreal forests, were used to test our hypotheses in two steps. (1) Stepwise regressions were used to identify the best explanatory variables for tree productivity. (2) The selected climatic and environmental variables, as well as density and biodiversity indices, were included in a structural equation model where links (paths) between covarying variables are made explicit, making structural equation modelling the best tool to explore such complicated causal networks. Results This is the first large‐scale demonstration of a strong, positive and significant effect of biodiversity on tree productivity with control for climatic and environmental conditions. Important differences were noted between the two forest biomes investigated. Main conclusions We show for the first time that complementarity may be less important in temperate forests growing in a more stable and productive environment where competitive exclusion is the most probable outcome of species interactions, whereas in the more stressful environment of boreal forests, beneficial interactions between species may be more important. The present work is also a framework for the analysis of large datasets in biodiversity–ecosystem functioning (B‐EF) research.     

儿童与成人慢性乙型肝炎患者乙型肝炎病毒Core基因区准种特征及正选择压力差异分析

儿童与成人慢性乙型肝炎患者的临床特征差异明显。乙型肝炎病毒(Hepatitis B virus, HBV)病毒准种特征与其致病特性紧密相连,HBV病毒Core 基因区富含免疫表位,该区域的准种特征直接反映病毒变异与病毒应对宿主免疫压力间的动态过程。文章通过扩增170名儿童慢性乙型肝炎患者及121名成人慢性乙型肝炎患者病毒Core基因区,按照病毒基因型以及病毒e抗原(Hepatitis B virus e antigen, HBeAg)状态进行分组,使用序列复杂度、多样性、非同义突变率(Non-synonymous substitution ratio,dN)、同义突变率(Synonymous substitution ratios , dS)等指标衡量不同组别之间的病毒准种特征;使用不同模型计算不同组别中受到正选择压力的位点,进一步结合HBV Core基因区免疫表位信息,进行正选择位点的定位分析。结果发现,儿童乙型肝炎病毒患者体内病毒Core基因区序列复杂性和多样性低于成人患者,且前者Core基因区正选择位点个数显著低于后者,这说明儿童慢性乙型肝炎患者体内病毒受到的选择压力低于成人患者。在儿童及成人慢性感染病人组中,HBeAg阳性病人体内病毒受到的选择压力低于HBeAg阴性病人。儿童及成人慢性感染患者体内病毒存在13个正选择位点,大多数正选择位点位于已知的抗原表位上。本研究从分子进化角度揭示了儿童与成人慢性乙型肝炎病例体内病毒Core基因区序列准种差异,为两类病人显著不同的临床表征提供了群体遗传学的解释。     

Genetic diversity analysis of elite European maize (Zea mays L.) inbred lines using AFLP, SSR, and SNP markers reveals ascertainment bias for a subset of SNPs

Recent advances in high-throughput sequencing technologies have triggered a shift toward single-nucleotide polymorphism (SNP) markers. A systematic bias can be introduced if SNPs are ascertained in a small panel of genotypes and then used for characterizing a larger population (ascertainment bias). With the objective of evaluating a potential ascertainment bias of the Illumina MaizeSNP50 array with respect to elite European maize dent and flint inbred lines, we compared the genetic diversity among these materials based on 731 amplified fragment length polymorphisms (AFLPs), 186 simple sequence repeats (SSRs), 41,434 SNPs of the MaizeSNP50 array (SNP-A), and two subsets of it, i.e., 30,068 Panzea (SNP-P) and 11,366 Syngenta markers (SNP-S). We evaluated the bias effects on major allele frequency, allele number, gene diversity, modified Roger’s distance (MRD), and on molecular variance (AMOVA). We revealed ascertainment bias in SNP-A, compared to AFLPs and SSRs. It affected especially European flint lines analyzed with markers (SNP-S) specifically developed to maximize differences among North American dent germplasm. The bias affected all genetic parameters, but did not substantially alter the relative distances between inbred lines within groups. For these reasons, we conclude that the SNP markers of the MaizeSNP50 array can be employed for breeding purposes in the investigated material. However, attention should be paid in case of comparisons between genotypes belonging to different heterotic groups. In this case, it is advisable to prefer a marker subset with potentially low ascertainment bias, like in our case the SNP-P marker set.