Genetic Variation

遗传变异
  • 文章类型: Journal Article
    尽管进化生物学痴迷于自然选择,很少有研究在自然种群的全基因组尺度上评估多代系列的选择模式。这里,我们报道了一项10年的微甲壳类水蚤种群基因组调查。[公式:参见文本]800个分离株的基因组序列提供了对无法从长期分子进化研究中获得的选择模式的见解,包括以下内容:整个基因组中接近准中性的普遍性(接近零的平均净选择系数,但是均值的时间差异很大,几乎没有证据表明跨时间间隔的选择正协方差);弱的正选择对次要等位基因起作用的优势;以及影响核苷酸多样性水平的许多可观察选择的小连锁岛的全基因组分布。这些结果表明,年际波动选择是自然种群变化水平的主要决定因素,挑战解释核苷酸多样性和分歧模式的传统范式,并激发了进一步发展解释群体基因组数据的理论表达式的必要性。
    Despite evolutionary biology\'s obsession with natural selection, few studies have evaluated multigenerational series of patterns of selection on a genome-wide scale in natural populations. Here, we report on a 10-y population-genomic survey of the microcrustacean Daphnia pulex. The genome sequences of [Formula: see text]800 isolates provide insights into patterns of selection that cannot be obtained from long-term molecular-evolution studies, including the following: the pervasiveness of near quasi-neutrality across the genome (mean net selection coefficients near zero, but with significant temporal variance about the mean, and little evidence of positive covariance of selection across time intervals); the preponderance of weak positive selection operating on minor alleles; and a genome-wide distribution of numerous small linkage islands of observable selection influencing levels of nucleotide diversity. These results suggest that interannual fluctuating selection is a major determinant of standing levels of variation in natural populations, challenge the conventional paradigm for interpreting patterns of nucleotide diversity and divergence, and motivate the need for the further development of theoretical expressions for the interpretation of population-genomic data.
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  • 文章类型: Journal Article
    Phoresy是一种种间相互作用,通过附着于更具流动性的物种来促进空间分散。搭便车的物种已经进化出身体接触和成功对抗的特定特征,但是涉及这些特征及其进化的调节机制在很大程度上尚未被探索。线虫秀丽隐杆线虫在其应激诱导的发育阶段表现出一种搭便车行为,称为“顺风车”。Dauer特异性的咀嚼行为在自然秀丽隐杆线虫种群中具有重要作用,经历了繁荣与萧条的人口动态。在这项研究中,我们调查了在世界各地采样的137个野生秀丽隐杆线虫菌株的优良行为。我们确定了物种范围内的自然变异,并进行了全基因组关联作图。我们显示nta-1启动子中的变体,编码推定的类固醇生成酶,在回音方面存在差异。这种差异是由于神经胶质细胞中nta-1表达的变化,这意味着神经胶质类固醇代谢调节电泳行为。种群遗传分析和地理分布模式表明,平衡选择维持了祖先C.elegans种群中存在的两个nta-1单倍型。我们的发现有助于进一步了解物种相互作用的分子机制以及维持自然种群内的遗传多样性。
    Phoresy is an interspecies interaction that facilitates spatial dispersal by attaching to a more mobile species. Hitchhiking species have evolved specific traits for physical contact and successful phoresy, but the regulatory mechanisms involved in such traits and their evolution are largely unexplored. The nematode Caenorhabditis elegans displays a hitchhiking behavior known as nictation during its stress-induced developmental stage. Dauer-specific nictation behavior has an important role in natural C. elegans populations, which experience boom-and-bust population dynamics. In this study, we investigated the nictation behavior of 137 wild C. elegans strains sampled throughout the world. We identified species-wide natural variation in nictation and performed a genome-wide association mapping. We show that the variants in the promoter of nta-1, encoding a putative steroidogenic enzyme, underlie differences in nictation. This difference is due to the changes in nta-1 expression in glial cells, which implies that glial steroid metabolism regulates phoretic behavior. Population genetic analysis and geographic distribution patterns suggest that balancing selection maintained two nta-1 haplotypes that existed in ancestral C. elegans populations. Our findings contribute to further understanding of the molecular mechanism of species interaction and the maintenance of genetic diversity within natural populations.
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  • 文章类型: Journal Article
    anatolicumHyalommaanatolicum,安纳托利亚硬蜱是一种公认的媒介,涉及各种病原体向动物和人类的传播。本研究基于线粒体大亚基核糖体RNA(16SrRNA)基因序列,阐明了土豆菌的种群结构和单倍型网络。GenBank中存档的75个序列的种群结构和单倍型网络分析,包括本文生成的15个序列,产生24单倍型。单倍型1(Hap_1)是由来自印度的45个序列组成的主要单倍型,中国,巴基斯坦,土耳其,埃及,伊拉克,塔吉克斯坦。完整的单倍型网络表现出星状构象,突出了最近的人口扩张。整个数据集,以及对应于印度的序列,中国,巴基斯坦,显示出高单倍型(分别为0.638±0.065、0.671±0.103、0.753±0.099和0.854±0.061)和低核苷酸(分别为0.00407±0.00090、0.00525±0.00196、0.00680±0.00233和0.00453±0.00056)多样性,进一步强调了最近的人口扩张。包括田岛的D在内的中立性指数,傅和丽的D,完整数据集(分别为-2.661,-6.008和-5.649)以及来自印度的序列(分别为-2.223,-3.414和-3.567)的Fu和Li\的F为阴性,表明偏离中立和最近的人口膨胀。本研究提供了基于线粒体16SrRNA基因的种群结构和单倍型网络的新见解。不同的测试推断遗传分化较低,并表明这种经济上重要的蜱物种最近种群扩大。
    Hyalomma anatolicum, an Anatolian hard tick is a well-recognized vector involved in the transmission of various pathogens to animals and humans. The present study elucidated the population structure and haplotype network of H. anatolicum based on the mitochondrial large subunit ribosomal RNA (16S rRNA) gene sequence. The population structure and haplotype network analysis of 75 sequences archived in the GenBank, including the 15 sequences generated herein, yielded 24 haplotypes. Haplotype 1 (Hap_1) was the predominant haplotype consisting of 45 sequences from India, China, Pakistan, Turkey, Egypt, Iraq, and Tajikistan. The complete haplotype network exhibited a stellate conformation, highlighting a recent population expansion. The overall dataset, together with the sequences corresponding to India, China, and Pakistan, showed a high haplotype (0.638 ± 0.065, 0.671 ± 0.103, 0.753 ± 0.099, and 0.854 ± 0.061, respectively) and low nucleotide (0.00407 ± 0.00090, 0.00525 ± 0.00196, 0.00680 ± 0.00233, and 0.00453 ± 0.00056, respectively) diversity, further emphasized a recent population expansion. The neutrality indices including Tajima\'s D, Fu and Li\'s D, and Fu and Li\'s F for the complete dataset (- 2.661, - 6.008, and - 5.649, respectively) as well as for the sequences from India (- 2.223, - 3.414, and - 3.567, respectively) were negative, suggesting deviation from neutrality and a recent population expansion. The present study provided novel insights into the population structure and haplotype networks of H. anatolicum based on the mitochondrial 16S rRNA gene, and the different tests inferred a low genetic differentiation and suggested a recent population expansion of this economically important tick species.
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  • 文章类型: Journal Article
    力场X(FFX)是一个开源软件包,用于遗传变异和有机晶体的原子分辨率建模,利用先进的势能函数和实验数据。FFX目前由九个模块化软件包组成,这些软件包具有新颖的算法,包括通过多体扩展进行全局优化,使用可极化恒定pH分子动力学的酸碱化学,自由能差的估计,广义柯克伍德隐式溶剂模型,还有更多。FFX的应用重点是晶体结构预测管道的使用和开发,针对实验数据集的生物分子结构改进,以及估计遗传变异对蛋白质和核酸的热力学影响。并行Java和OpenMM的使用结合提供共享内存,消息传递,和图形处理单元并行化,以实现高性能仿真。总的来说,FFX平台用作计算显微镜,研究从有机晶体到溶剂化生物分子系统的系统。
    Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.
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  • 文章类型: Journal Article
    在圣卡塔琳娜发现死亡的南美海狮中检测到了进化枝2.3.4.4b高致病性禽流感(HPAI)H5N1病毒,巴西,2023年10月。进行了全基因组测序和比较系统发育分析,以调查起源,遗传多样性,和H5N1病毒的人畜共患潜力。H5N1病毒属于进化枝2.3.4.4bH5N1病毒的B3.2基因型,在北美发现并传播到南美。它们获得了与哺乳动物宿主亲和力相关的新氨基酸取代。我们的研究提供了对巴西H5N1病毒的遗传景观的见解,强调了有助于它们可能适应哺乳动物宿主的连续进化过程。
    Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.
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  • 文章类型: Journal Article
    结论:通过测序对全球723种黄瓜遗传资源进行基因分型显示,黄瓜通过至少三种不同的途径向东分散,一个到东南亚,两个从不同的方向到东亚。黄瓜(Cucumissativus)是世界范围内种植和消费的重要经济蔬菜作物。尽管它很受欢迎,黄瓜从南亚的起源分散到世界其他地方的方式,尤其是在东方,由于缺乏书面记录,仍然是一个谜。在这项研究中,我们对全球723个黄瓜品种进行了基因分型测序(GBS),主要存放在日本国家农业和粮食研究组织(NARO)Genebank,来表征它们的遗传多样性,关系,和人口结构。基于GBS鉴定的超过60,000个全基因组单核苷酸多态性的分析显示,东南亚和东亚人群之间存在明显的遗传差异。表明他们独立到达各自的地区,不是渐进的。对东亚种群进行了更深入的调查,发现了两个具有不同果实特征的亚种群,支持将东亚黄瓜传统分类为两种类型,这些类型被认为是通过独立路线引入的。最后,我们开发了一个包含100个种质的核心集合,代表了整个集合中至少93.2%的遗传多样性。遗传关系和种群结构,它们与地理分布和表型特征的关联,本研究提供的核心馆藏是阐明黄瓜传播历史和促进遗传资源有效利用和管理的宝贵资源,可用于黄瓜研究和育种。
    CONCLUSIONS: Genotyping-by-sequencing of 723 worldwide cucumber genetic resources revealed that cucumbers were dispersed eastward via at least three distinct routes, one to Southeast Asia and two from different directions to East Asia. The cucumber (Cucumis sativus) is an economically important vegetable crop cultivated and consumed worldwide. Despite its popularity, the manner in which cucumbers were dispersed from their origin in South Asia to the rest of the world, particularly to the east, remains a mystery due to the lack of written records. In this study, we performed genotyping-by-sequencing (GBS) on 723 worldwide cucumber accessions, mainly deposited in the Japanese National Agriculture and Food Research Organization (NARO) Genebank, to characterize their genetic diversity, relationships, and population structure. Analyses based on over 60,000 genome-wide single-nucleotide polymorphisms identified by GBS revealed clear genetic differentiation between Southeast and East Asian populations, suggesting that they reached their respective region independently, not progressively. A deeper investigation of the East Asian population identified two subpopulations with different fruit characteristics, supporting the traditional classification of East Asian cucumbers into two types thought to have been introduced by independent routes. Finally, we developed a core collection of 100 accessions representing at least 93.2% of the genetic diversity present in the entire collection. The genetic relationships and population structure, their associations with geographic distribution and phenotypic traits, and the core collection presented in this study are valuable resources for elucidating the dispersal history and promoting the efficient use and management of genetic resources for research and breeding in cucumber.
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  • 文章类型: Journal Article
    Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies have been carried out to determine the role of animals in its transmission. In Mali, it has been over three decades since the last molecular study of animal schistosomes was carried out. It is now urgent to identify circulating strains of the parasite because of potential interactions with other schistosome species, which could complicate disease control. The aim of our work was to study the composition and genetic structure of schistosome populations collected from cattle. The prevalence of schistosome was 23.9%, with the prevalences of Schistosoma bovis (Sb) and S. curassoni (Sc) estimated at 12.6% and 9.8%, respectively. No hybrid strains or S. haematobium were found. The parasites displayed distinct geographical distribution with Sb dominant in Bamako (78.8% and 98% in Central Bamako Slaughterhouse and Sabalibougou Slaughterhouses, respectively) and Sc dominant in Kayes (95.3%). Of the 476 parasites with a complete genetic profile, 60.4% were pure Sc, and were mainly from Kayes. We identified two clusters at the site level (Fst of 0.057 and 0.042 for Sb and Sc, respectively). Cluster 1 was predominantly composed of pure Sb parasites and cluster 2 was mainly composed of pure Sc parasites, from Bamako and Kayes, respectively. Our study shows that cattle schistosomiasis remains endemic in Mali with S. bovis and S. curassoni. A robust genetic structure between the different schistosome populations was identified, which included two clusters based on the geographical distribution of the parasites.
    UNASSIGNED: Structure génétique des populations de Schistosoma bovis et S. curassoni collectées chez des bovins au Mali.
    UNASSIGNED: La schistosomiase revêt une grande importance médicale et vétérinaire. Malgré la situation critique de la schistosomiase en Afrique subsaharienne, peu d’études épidémiologiques moléculaires ont été réalisées pour déterminer le rôle des animaux dans sa transmission. Au Mali, cela fait plus de trois décennies que la dernière étude moléculaire des schistosomes animaux a été réalisée. Il est désormais urgent d’identifier les souches circulantes du parasite en raison des interactions potentielles avec d’autres espèces de schistosomes, ce qui pourrait compliquer la lutte contre la maladie. Le but de notre travail était d’étudier la composition et la structure génétique des populations de schistosomes collectées chez des bovins. La prévalence des schistosomes était de 23,9 %, celles de Schistosoma bovis (Sb) et de S. curassoni (Sc) étant respectivement estimées à 12,6 % et 9,8 %. Aucune souche hybride ni S. haematobium n’ont été trouvés. Les parasites présentaient une répartition géographique distincte avec Sb dominant à Bamako (respectivement 78,8 % et 98 % aux Abattoirs Centraux de Bamako et aux Abattoirs de Sabalibougou) et Sc dominant à Kayes (95,3 %). Sur les 476 parasites ayant un profil génétique complet, 60,4 % étaient des Sc purs, et provenaient principalement de Kayes. Nous avons identifié deux clusters au niveau du site (Fst de 0,057 et 0,042 pour Sb et Sc, respectivement). Le groupe 1 était principalement composé de parasites Sb purs et le groupe 2 était principalement composé de parasites Sc purs, provenant respectivement de Bamako et de Kayes. Notre étude montre que la schistosomiase bovine reste endémique au Mali, avec S. bovis and S. curassoni. Une structure génétique robuste entre les différentes populations de schistosomes a été identifiée, comprenant deux groupes basés sur la répartition géographique des parasites.
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  • 文章类型: Journal Article
    Cressdnaviricota由大量环状Rep编码单链(CRESS)DNA病毒组成。最近,宏基因组分析揭示了它们在各种真核生物中的普遍分布。与人类CRESS-DNA病毒有关的数据仍然很少。我们的研究调查了人阴道分泌物中CRESS-DNA病毒的存在和遗传多样性。从纽约市生育诊所就诊的28名29至43岁的女性中收集了阴道拭子。进行了探索性宏基因组分析,并通过分析病毒分离株的近全长序列证实了CRESS-DNA病毒的检测。系统发育树基于CRESS-DNA病毒基因组的REP开放阅读框序列。在16名(57.1%)女性中鉴定出11个几乎完整的CRESS-DNA病毒基因组。这些病毒的存在与任何人口统计学或临床参数之间没有关联。系统发育分析表明,其中一个序列属于基因组病毒科中的双环病毒属,而十个序列代表以前未分类的CRESS-DNA病毒物种。CRESS-DNA病毒的新物种存在于成年女性的阴道中。虽然他们是短暂的共生特工,他们在该站点的存在的潜在临床意义不能被忽略.
    The Phylum Cressdnaviricota consists of a large number of circular Rep-encoding single-stranded (CRESS)-DNA viruses. Recently, metagenomic analyzes revealed their ubiquitous distribution in a diverse range of eukaryotes. Data relating to CRESS-DNA viruses in humans remains scarce. Our study investigated the presence and genetic diversity of CRESS-DNA viruses in human vaginal secretions. Vaginal swabs were collected from 28 women between 29 and 43 years old attending a fertility clinic in New York City. An exploratory metagenomic analysis was performed and detection of CRESS-DNA viruses was confirmed through analysis of near full-length sequences of the viral isolates. A phylogenetic tree was based on the REP open reading frame sequences of the CRESS-DNA virus genome. Eleven nearly complete CRESS-DNA viral genomes were identified in 16 (57.1%) women. There were no associations between the presence of these viruses and any demographic or clinical parameters. Phylogenetic analysis indicated that one of the sequences belonged to the genus Gemycircularvirus within the Genomoviridae family, while ten sequences represented previously unclassified species of CRESS-DNA viruses. Novel species of CRESS-DNA viruses are present in the vaginal tract of adult women. Although they be transient commensal agents, the potential clinical implications for their presence at this site cannot be dismissed.
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  • 文章类型: Journal Article
    根据最近通过的《昆明-蒙特利尔全球生物多样性框架》,196个缔约方承诺报告所有物种的遗传多样性状况。为了便于报告,开发了三个遗传多样性指标,其中两个侧重于有助于遗传多样性保护的过程:保持遗传上不同的种群和确保种群足够大,以保持遗传多样性。这些指标的主要优点是可以在有或没有基于DNA的数据的情况下进行估计。然而,证明其可行性需要解决使用从不同来源收集的数据的方法挑战,在不同的分类群体中,以及社会经济地位和生物多样性水平不同的国家。这里,我们评估了919个分类单元的遗传指标,代表9个国家的5271人,包括庞大的国家和发展中经济体。被评估的分类单元中有83%的数据可用于计算至少一个指标。我们的结果表明,尽管大多数物种保持大多数种群,58%的物种种群太小,无法保持遗传多样性。此外,遗传指标值表明IUCN红色名录状态和其他举措未能评估遗传状态,强调遗传指标的重要性。
    Under the recently adopted Kunming-Montreal Global Biodiversity Framework, 196 Parties committed to reporting the status of genetic diversity for all species. To facilitate reporting, three genetic diversity indicators were developed, two of which focus on processes contributing to genetic diversity conservation: maintaining genetically distinct populations and ensuring populations are large enough to maintain genetic diversity. The major advantage of these indicators is that they can be estimated with or without DNA-based data. However, demonstrating their feasibility requires addressing the methodological challenges of using data gathered from diverse sources, across diverse taxonomic groups, and for countries of varying socio-economic status and biodiversity levels. Here, we assess the genetic indicators for 919 taxa, representing 5271 populations across nine countries, including megadiverse countries and developing economies. Eighty-three percent of the taxa assessed had data available to calculate at least one indicator. Our results show that although the majority of species maintain most populations, 58% of species have populations too small to maintain genetic diversity. Moreover, genetic indicator values suggest that IUCN Red List status and other initiatives fail to assess genetic status, highlighting the critical importance of genetic indicators.
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  • 文章类型: Journal Article
    背景:计算变异效应预测因子为解释人类遗传变异提供了一种可扩展且越来越可靠的方法,但是对循环性和偏差的担忧限制了以前评估和比较预测因子的方法。尚未在预测训练中使用的基因分型和表型参与者的群体水平队列可以促进可用方法的无偏见基准测试。使用一组经过策划的人类基因-性状关联与报道的罕见变异负担关联,在UKBiobank和AllofUs队列中,我们评估了24个计算变异效应预测因子与相关人类性状的相关性.
    结果:AlphaMissense在基于UKBiobank和AllofUs参与者的罕见错义变异推断人类特征方面优于所有其他预测因子。这两个队列中计算变异效应预测因子的总体排名显示出显着的正相关。
    结论:我们描述了一种评估计算变量效应预测因子的方法,该方法避开了先前评估的局限性。这种方法可推广到未来的预测因子,并可以继续为个人和临床遗传学的预测因子选择提供信息。
    Computational variant effect predictors offer a scalable and increasingly reliable means of interpreting human genetic variation, but concerns of circularity and bias have limited previous methods for evaluating and comparing predictors. Population-level cohorts of genotyped and phenotyped participants that have not been used in predictor training can facilitate an unbiased benchmarking of available methods. Using a curated set of human gene-trait associations with a reported rare-variant burden association, we evaluate the correlations of 24 computational variant effect predictors with associated human traits in the UK Biobank and All of Us cohorts.
    AlphaMissense outperformed all other predictors in inferring human traits based on rare missense variants in UK Biobank and All of Us participants. The overall rankings of computational variant effect predictors in these two cohorts showed a significant positive correlation.
    We describe a method to assess computational variant effect predictors that sidesteps the limitations of previous evaluations. This approach is generalizable to future predictors and could continue to inform predictor choice for personal and clinical genetics.
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