genomic diversity

基因组多样性
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    脆弱拟杆菌是人类结肠中常见的革兰氏阴性共生细菌,分为两个基因组,称为I和II。通过全面收集694个脆弱芽孢杆菌全基因组序列,我们确定了区分这些划分的新颖特征。我们的研究揭示了一个独特的地理分布,主要在北美发现I种菌株,在亚洲发现II种菌株。此外,II类菌株更经常与血流感染相关,表明有明显的致病潜力。我们报告了与代谢相关的基因丰度的两种划分之间的差异,毒力,应激反应,和殖民战略。值得注意的是,II级菌株比I级菌株具有更多的抗菌素耐药性(AMR)基因。这些发现为I区和II区菌株的功能作用提供了新的见解,指示肠道内的特殊生态位和肠外部位的潜在致病作用。
    目的:了解肠道微生物群中微生物种类的独特功能对于破译它们对人类健康的影响至关重要。将II类菌株分类为脆弱拟杆菌可能导致错误的关联,因为研究人员可能错误地将II类菌株中观察到的特征归因于更广泛研究的IB.fragilis。我们的发现强调了将这些分裂视为具有不同功能的独立物种的必要性。我们揭示了在与肠道定植和生存策略相关的基因中,I区和II区菌株之间的差异基因患病率的新发现。潜在影响它们作为肠道共生的作用及其在肠外部位的致病性。尽管这些群体之间存在显著的生态位重叠和定殖模式,我们的研究强调了控制应变分布和行为的复杂动力学,强调需要对这些微生物有细微的了解。
    Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 B. fragilis whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites.
    OBJECTIVE: Understanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as Bacteroides fragilis can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I B. fragilis. Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms.
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  • 文章类型: Journal Article
    四川-云南地区是中国西南地区牦牛的主要产区,牦牛具有丰富的遗传资源。然而,对西藏和中国西南部整个牦牛种群的遗传特征研究有限。在这项研究中,我们进行了全基因组重测序,以鉴定来自四川六个牦牛品种(种群)的198个个体的遗传变异信息(木里牦牛,金川牦牛,长泰牦牛,麦瓦牦牛),云南(中甸牦牛),西藏(西藏牦牛)目的是调查全基因组遗传多样性,种群遗传结构,和基因组选择签名。我们观察到所有六个种群都表现出丰富的遗传多样性。除了藏牦牛,显示低核苷酸多样性(0.00104),其余牦牛种群通常表现出高度的核苷酸多样性(0.00129-0.00153)。群体遗传结构分析表明,在六个牦牛种群中,木里牦牛表现出与其他牦牛种群的更大差异,并独立形成了一个不同的簇。麦瓦牦牛群体表现出复杂的遗传结构,并与金川牦牛和长泰牦牛发生基因交换。在与生长相关的候选基因(GNB4,HMGA2,TRPS1和LTBP1)中检测到阳性选择信号,繁殖(PI4KB,DYNC1I1和GRIP1),免疫(CD200和IL1RAP),泌乳(SNX13和CPM),低氧适应(NDUFB6,PRKN,和MRPS9),头发(KRT24、KRT25和KRT26),肉质(SUCLG2),消化吸收(CLDN1),和颜料沉积(OCA2)使用积分Pi和FST方法。这项研究为了解西藏和中国西南部牦牛种群的全基因组遗传特征提供了重要的见解。
    The Sichuan-Yunnan region is the main production area of yaks in southwestern China, with rich genetic resources of Yaks. Nevertheless, there have been limited study on the genetic characteristics of the entire yak populations in Tibet and southwestern China. In this study, we performed whole-genome resequencing to identify genetic variation information in a total of 198 individuals from six yak breeds (populations) in Sichuan (Muli yak, Jinchuan yak, Changtai yak, Maiwa yak), Yunnan (Zhongdian yak), and Tibet (Tibetan yak). The aim was to investigate the whole-genome genetic diversity, population genetic structure, and genome selection signatures. We observed that all six populations exhibit abundant genetic diversity. Except for Tibetan yaks, which showed low nucleotide diversity (0.00104), the remaining yak populations generally displayed high nucleotide diversity (0.00129-0.00153). Population genetic structure analysis revealed that, among the six yak populations, Muli yak exhibited greater differentiation from other yak populations and formed a distinct cluster independently. The Maiwa yak population displayed a complex genetic structure and exhibited gene exchange with Jinchuan and Changtai yaks. Positive selection signals were detected in candidate genes associated with growth (GNB4, HMGA2, TRPS1, and LTBP1), reproduction (PI4KB, DYNC1I1, and GRIP1), immunity (CD200 and IL1RAP), lactation (SNX13 and CPM), hypoxia adaptation (NDUFB6, PRKN, and MRPS9), hair (KRT24, KRT25, and KRT26), meat quality (SUCLG2), digestion and absorption (CLDN1), and pigment deposition (OCA2) using the integrated Pi and F ST methods. This study provides significant insights into understanding the whole-genome genetic characteristics of yak populations in Tibet and southwestern China.
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  • 文章类型: Journal Article
    拉脱维亚黑头羊是当地唯一开发的绵羊品种。该品种是在20世纪初通过将当地的粗毛绵羊与英国的什罗普郡和牛津郡品种杂交而形成的。后来通过添加法兰西岛对该品种进行了改良,Texel,德国黑头,和Finnsheep,以实现更高的繁殖力和更好的肉质。先前的研究表明,拉脱维亚黑头绵羊与爱沙尼亚和立陶宛黑脸品种密切相关,根据微卫星数据。为了扩大我们对拉脱维亚黑头品种遗传资源的认识,我们对40只本地绵羊进行了全基因组重测序分析。调查表明,当地绵羊的遗传多样性水平与其他改良的欧洲品种相似,包括Charollais和Suffolk.拉脱维亚黑头绵羊的全基因组核苷酸多样性(π)为3.91×10-3,而在不相关个体的子样本中,在40只动物中观察到的平均杂合性为0.267和0.438。Ne在十代前迅速下降到200,最近下降到四代前的Ne73。然而,基于纯合性运行的近交水平为,平均而言,低,FROH范围在0.016和0.059之间。对该品种基因组组成的分析证实了与英国血统的绵羊的共同血统,反映了该品种的历史。然而,拉脱维亚黑头绵羊在遗传上是可分离的。当代拉脱维亚黑头绵羊种群的遗传多样性,近亲繁殖率低。然而,必须进一步发展品种管理计划,以防止近亲繁殖的增加,遗传多样性的丧失,以及特定品种遗传资源的枯竭,确保拉脱维亚本土黑头羊的保存。
    The Latvian Darkheaded is the only locally developed sheep breed. The breed was formed at the beginning of the 20th century by crossing local coarse-wooled sheep with the British Shropshire and Oxfordshire breeds. The breed was later improved by adding Ile-de-France, Texel, German blackheads, and Finnsheep to achieve higher prolificacy and better meat quality. Previous studies have reported the Latvian Darkheaded sheep to be closely related to Estonian and Lithuanian Blackface breeds, according to microsatellite data. To expand our knowledge of the genetic resources of the Latvian Darkheaded breed, we conducted a whole-genome resequencing analysis on 40 native sheep. The investigation showed that local sheep harbor genetic diversity levels similar to those observed among other improved breeds of European origin, including Charollais and Suffolk. Genome-wide nucleotide diversity (π) in Latvian Darkheaded sheep was 3.91 × 10-3, whereas the average observed heterozygosity among the 40 animals was 0.267 and 0.438 within the subsample of unrelated individuals. The Ne has rapidly decreased to 200 ten generations ago with a recent drop to Ne 73 four generations ago. However, inbreeding levels based on runs of homozygosity were, on average, low, with FROH ranging between 0.016 and 0.059. The analysis of the genomic composition of the breed confirmed shared ancestry with sheep of British origin, reflecting the history of the breed. Nevertheless, Latvian Darkheaded sheep were genetically separable. The contemporary Latvian Darkheaded sheep population is genetically diverse with a low inbreeding rate. However, further development of breed management programs is necessary to prevent an increase in inbreeding, loss of genetic diversity, and depletion of breed-specific genetic resources, ensuring the preservation of the native Latvian Darkheaded sheep.
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  • 文章类型: Journal Article
    TwinsMX注册是墨西哥的一项国家研究计划,旨在了解遗传与环境之间复杂的相互作用,以塑造该国人口的身心健康特征。通过多学科的方法,TwinsMX旨在提高我们对复杂特征和疾病中种族差异的遗传和环境机制的认识,包括行为,心理测量学,人体测量学,新陈代谢,心血管和精神障碍。从2800多名双胞胎那里收集到的信息,本文更新了几种复杂特征的普遍性;并描述了我们实施的进展和新颖的想法,例如磁共振成像。TwinsMX注册表的未来扩展将增强我们对遗传与环境之间在塑造墨西哥人口健康和疾病方面的复杂相互作用的理解。总的来说,这份报告描述了建立一个可靠数据库的进展,该数据库将允许研究墨西哥人口的复杂特征,不仅对我们的财团有价值,而且对于全世界的科学界来说,通过提供对未充分研究的基因混合人群的新见解。
    TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country\'s population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations.
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  • 文章类型: Journal Article
    背景:由于黄曲霉产生致癌黄曲霉毒素,因此黄曲霉是重要的农业和食品安全威胁。它具有高度的遗传多样性,适应各种环境。最近,我们报道了黄曲霉分离株的两个参考基因组,AF13(MAT1-2和高度黄曲霉毒素分离株)和NRRL3357(MAT1-1和中度黄曲霉毒素生产者)。Where,在AF13中插入310kb包括产生黄曲霉毒素的基因bZIP转录因子,名为atfC。观察到这些具有对比表型的分离株之间的显着基因组变异,促使人们对黄曲霉的其他农业分离株之间的变异进行了研究,目的是发现可能与黄曲霉毒素生产调节相关的新基因。本研究的设计有三个主要目标:(1)从包括玉米植物和田间土壤在内的各种来源收集大量黄曲霉分离株;(2)收集的分离株的全基因组测序和pangenome的开发;(3)全基因组关联研究(Pan-GWAS)以鉴定新的次生代谢簇基因。
    结果:对346个黄曲霉分离株的全基因组分析鉴定出总共17,855个独特的直系同源基因簇,只有41%(7,315)的核心基因和59%(10,540)的辅助基因表明在驯化过程中积累了高基因组多样性。美国专利5,994号附属基因组中的直向同源基因簇未在黄曲霉AF13或NRRL3357参考基因组中注释。基因组变异的全基因组关联分析确定了391个与黄曲霉毒素产生相关的显著相关的全基因。有趣的是,大多数显著相关的泛基因(94%;369个关联)属于辅助基因组,表明基因组扩增导致与黄曲霉毒素和其他次级代谢产物相关的新基因的掺入.
    结论:总之,这项研究提供了完整的pangenome框架的物种黄曲霉以及相关基因的病原体生存和黄曲霉毒素的生产。大的辅助基因组表明物种A.flavus的基因组多样性很大,然而,AflaPan是一个封闭的pangenome,代表了黄曲霉物种的最佳多样性。最重要的是,新发现的黄曲霉毒素产生基因簇将成为寻求黄曲霉毒素缓解策略的新来源,需要在研究中给予新的关注。
    BACKGROUND: Aspergillus flavus is an important agricultural and food safety threat due to its production of carcinogenic aflatoxins. It has high level of genetic diversity that is adapted to various environments. Recently, we reported two reference genomes of A. flavus isolates, AF13 (MAT1-2 and highly aflatoxigenic isolate) and NRRL3357 (MAT1-1 and moderate aflatoxin producer). Where, an insertion of 310 kb in AF13 included an aflatoxin producing gene bZIP transcription factor, named atfC. Observations of significant genomic variants between these isolates of contrasting phenotypes prompted an investigation into variation among other agricultural isolates of A. flavus with the goal of discovering novel genes potentially associated with aflatoxin production regulation. Present study was designed with three main objectives: (1) collection of large number of A. flavus isolates from diverse sources including maize plants and field soils; (2) whole genome sequencing of collected isolates and development of a pangenome; and (3) pangenome-wide association study (Pan-GWAS) to identify novel secondary metabolite cluster genes.
    RESULTS: Pangenome analysis of 346 A. flavus isolates identified a total of 17,855 unique orthologous gene clusters, with mere 41% (7,315) core genes and 59% (10,540) accessory genes indicating accumulation of high genomic diversity during domestication. 5,994 orthologous gene clusters in accessory genome not annotated in either the A. flavus AF13 or NRRL3357 reference genomes. Pan-genome wide association analysis of the genomic variations identified 391 significant associated pan-genes associated with aflatoxin production. Interestingly, most of the significantly associated pan-genes (94%; 369 associations) belonged to accessory genome indicating that genome expansion has resulted in the incorporation of new genes associated with aflatoxin and other secondary metabolites.
    CONCLUSIONS: In summary, this study provides complete pangenome framework for the species of Aspergillus flavus along with associated genes for pathogen survival and aflatoxin production. The large accessory genome indicated large genome diversity in the species A. flavus, however AflaPan is a closed pangenome represents optimum diversity of species A. flavus. Most importantly, the newly identified aflatoxin producing gene clusters will be a new source for seeking aflatoxin mitigation strategies and needs new attention in research.
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  • 文章类型: Journal Article
    “亚马逊临界点”是一种全球变化情景,导致大部分南部和东部亚马逊地区的大规模“草原化”取代了高地红土森林。过去,有人提出伴随最后一次冰川最大值(LGM)的降雨减少是这样的转折点,根据预测,随着干燥栖息地的扩大,栖息的物种应该会经历种群数量的减少。这里,我们使用亚马逊特有生物的全基因组(规模支持的蚂蚁-威利索尼斯属。)从该地区的9个人口中取样,以测试这一历史人口统计情景。来自亚马逊东南部和靠近亚马逊-塞拉多生态交错带的人口表现出广泛的人口统计模式,虽然大多数来自亚马逊北部和西部的人经历了400kya至80-60kya之间的均匀扩张,逐渐下降到20kya。威利索尼斯的东南种群是最后一个多样化的种群,与西部和北部种群相比,其杂合性较小,纯合性值较高。这些模式支持整个亚马逊地区的历史人口下降,这对南部和东部地区的血统产生了更强烈的影响。由于LGM期间较干燥和开放的植被广泛取代了潮湿的森林,因此存在历史上的“临界点”条件。
    The \"Amazon tipping point\" is a global change scenario resulting in replacement of upland terra-firme forests by large-scale \"savannization\" of mostly southern and eastern Amazon. Reduced rainfall accompanying the Last Glacial Maximum (LGM) has been proposed to have acted as such a tipping point in the past, with the prediction that terra-firme inhabiting species should have experienced reductions in population size as drier habitats expanded. Here, we use whole-genomes of an Amazonian endemic organism (Scale-backed antbirds - Willisornis spp.) sampled from nine populations across the region to test this historical demography scenario. Populations from southeastern Amazonia and close to the Amazon-Cerrado ecotone exhibited a wide range of demographic patterns, while most of those from northern and western Amazonia experienced uniform expansions between 400 kya and 80-60 kya, with gradual declines toward 20 kya. Southeastern populations of Willisornis were the last to diversify and showed smaller heterozygosity and higher runs of homozygosity values than western and northern populations. These patterns support historical population declines throughout the Amazon that affected more strongly lineages in the southern and eastern areas, where historical \"tipping point\" conditions existed due to the widespread replacement of humid forest by drier and open vegetation during the LGM.
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  • 文章类型: Journal Article
    单核细胞增生李斯特菌是乳制品加工设施中令人关注的食源性病原体,如果在产品中发现,有可能导致人类疾病并引发监管行动。李斯特菌的监测。建议通过环境采样来防止这些微生物在乳制品加工环境中的建立,从而降低产品污染的风险。为了告知单核细胞增生李斯特菌的多样性和传播,我们分析了通过不列颠哥伦比亚省乳品检验计划获得的单核细胞增生李斯特菌菌株(n=88)的基因组序列。在10年期间(2007-2017年),从五个不同的乳制品加工设施中回收了菌株。全基因组序列(WGS)的分析将分离株分为9种序列类型和11种cgMLST类型(CT)。大多数分离株(93%)属于谱系II。在每个CT中,分离株之间的单核苷酸多态性(SNP)差异在0到237之间。超过60个分离株的高度相似(0-16个SNP)簇,在一个设施内收集超过9年(#71),被确定为可能的持续种群。基因组含量的分析表明,与胁迫耐受性相关的基因频率较低,除广为传播的镉抗性基因cadA1和cadA2外。在分离株和设施中,毒力基因和内在蛋白基因内突变的分布各不相同。需要进一步的研究来阐明它们对致病性和应激反应的表型影响。这些发现证明了同一地区乳制品设施中单核细胞增生李斯特菌分离株的多样性。研究结果还表明,随着时间的推移,使用WGS来辨别单个设施内潜在的持久性事件。
    Listeria monocytogenes is a foodborne pathogen of concern in dairy processing facilities, with the potential to cause human illness and trigger regulatory actions if found in the product. Monitoring for Listeria spp. through environmental sampling is recommended to prevent establishment of these microorganisms in dairy processing environments, thereby reducing the risk of product contamination. To inform on L. monocytogenes diversity and transmission, we analyzed genome sequences of L. monocytogenes strains (n = 88) obtained through the British Columbia Dairy Inspection Program. Strains were recovered from five different dairy processing facilities over a 10 year period (2007-2017). Analysis of whole genome sequences (WGS) grouped the isolates into nine sequence types and 11 cgMLST types (CT). The majority of isolates (93%) belonged to lineage II. Within each CT, single nucleotide polymorphism (SNP) differences ranged from 0 to 237 between isolates. A highly similar (0-16 SNPs) cluster of over 60 isolates, collected over 9 years within one facility (#71), was identified suggesting a possible persistent population. Analyses of genome content revealed a low frequency of genes associated with stress tolerance, with the exception of widely disseminated cadmium resistance genes cadA1 and cadA2. The distribution of virulence genes and mutations within internalin genes varied across the isolates and facilities. Further studies are needed to elucidate their phenotypic effect on pathogenicity and stress response. These findings demonstrate the diversity of L. monocytogenes isolates across dairy facilities in the same region. Findings also showed the utility of using WGS to discern potential persistence events within a single facility over time.
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  • 文章类型: Journal Article
    强大的遗传结构引发了关于长颈鹿分类学的讨论,1,2,3包括将长颈鹿分为四个物种的建议:北部(长颈鹿),网状(G.C.网状),马赛(G.C.tippelskirchi),和南方长颈鹿(G.C.长颈鹿)。4,5,6然而,他们的进化史还没有完全解决,因为以前的研究使用简单的分叉模型,并且没有探索谱系之间基因流的存在或程度。因此,我们推断了一个模型,该模型结合了各种进化过程来评估当代长颈鹿多样性的驱动因素。我们分析了来自29个地区的90只野生长颈鹿的全基因组测序数据。最基本的差异可追溯到280kya。遗传分化,FST,在主要谱系中,范围在0.28和0.62之间,我们发现它们之间存在显着水平的古代基因流。特别是,一些分析表明,网状谱系是通过混合物进化而来的,北方血统和与马赛和南方长颈鹿有关的祖先血统几乎相等。这些新结果凸显了尽管基因流动但仍存在强烈分化的情况,为解释长颈鹿多样性和物种形成过程提供了进一步的背景。它们还说明,保护措施需要针对各种谱系和亚谱系,并且需要单独的管理策略来有效地保护长颈鹿的多样性。鉴于当地的灭绝和最近许多长颈鹿种群的急剧减少,这种对长颈鹿进化史的更好理解与保护干预措施有关,包括现有人口的重新引进和增援。
    Strong genetic structure has prompted discussion regarding giraffe taxonomy,1,2,3 including a suggestion to split the giraffe into four species: Northern (Giraffa c. camelopardalis), Reticulated (G. c. reticulata), Masai (G. c. tippelskirchi), and Southern giraffes (G. c. giraffa).4,5,6 However, their evolutionary history is not yet fully resolved, as previous studies used a simple bifurcating model and did not explore the presence or extent of gene flow between lineages. We therefore inferred a model that incorporates various evolutionary processes to assess the drivers of contemporary giraffe diversity. We analyzed whole-genome sequencing data from 90 wild giraffes from 29 localities across their current distribution. The most basal divergence was dated to 280 kya. Genetic differentiation, FST, among major lineages ranged between 0.28 and 0.62, and we found significant levels of ancient gene flow between them. In particular, several analyses suggested that the Reticulated lineage evolved through admixture, with almost equal contribution from the Northern lineage and an ancestral lineage related to Masai and Southern giraffes. These new results highlight a scenario of strong differentiation despite gene flow, providing further context for the interpretation of giraffe diversity and the process of speciation in general. They also illustrate that conservation measures need to target various lineages and sublineages and that separate management strategies are needed to conserve giraffe diversity effectively. Given local extinctions and recent dramatic declines in many giraffe populations, this improved understanding of giraffe evolutionary history is relevant for conservation interventions, including reintroductions and reinforcements of existing populations.
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  • 文章类型: Journal Article
    背景:说苗族(HM)的人与语言有关,主要生活在中国,但是对它们的祖先起源或形成基因组多样性的进化机制知之甚少。特别是,由于缺乏瑶族人群的全基因组测序数据,因此无法全面调查HM使用者的起源和进化史.因此,他们的起源是有争议的。
    结果:这里,我们对80个瑶族基因组进行了深度测序,我们的分析与28个东亚人口和968个古代亚洲基因组一起表明,HM语言家族的形成有很强的遗传基础。我们估计最近的共同祖先可以追溯到5800年前,而HM和Tai-Kadai使用者之间的遗传差异估计为8200年前。我们提出HM扬声器起源于长江流域,并与农业文明一起传播。我们确定了HM和汉族之间的高度分化变异,特别是,GJB2基因中与耳聋相关的错义变体(rs72474224)在HM说话者中的频率高于其他说话者。
    结论:我们的结果表明,人类人类的演化史涉及复杂的基因流和医学相关变异。
    BACKGROUND: Hmong-Mien (HM) speakers are linguistically related and live primarily in China, but little is known about their ancestral origins or the evolutionary mechanism shaping their genomic diversity. In particular, the lack of whole-genome sequencing data on the Yao population has prevented a full investigation of the origins and evolutionary history of HM speakers. As such, their origins are debatable.
    RESULTS: Here, we made a deep sequencing effort of 80 Yao genomes, and our analysis together with 28 East Asian populations and 968 ancient Asian genomes suggested that there is a strong genetic basis for the formation of the HM language family. We estimated that the most recent common ancestor dates to 5800 years ago, while the genetic divergence between the HM and Tai-Kadai speakers was estimated to be 8200 years ago. We proposed that HM speakers originated from the Yangtze River Basin and spread with agricultural civilization. We identified highly differentiated variants between HM and Han Chinese, in particular, a deafness-related missense variant (rs72474224) in the GJB2 gene is in a higher frequency in HM speakers than in others.
    CONCLUSIONS: Our results indicated complex gene flow and medically relevant variants involved in the HM speakers\' evolution history.
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