paleogenomics

古基因组学
  • 文章类型: Journal Article
    许多物种最近从濒临灭绝中恢复过来。尽管这些物种避免了直接的灭绝威胁,由于人口下降的潜在遗传后果,它们的长期生存能力仍然不稳定,在几代人以外的时间尺度上,人们对此知之甚少。大约10,000年前,猛犸象(Mammuthprimigenius)在Wrangel岛上与世隔绝,并持续了200多代,直到大约4,000年前灭绝。为了研究导致猛犸象灭绝的进化过程,我们分析了21个西伯利亚猛犸象的基因组.我们的结果表明,在随后的六千年中,人口迅速从严重的瓶颈中恢复过来,并在人口统计学上保持稳定。我们发现轻度有害突变逐渐积累,而高度有害的突变被清除,表明近亲繁殖的抑郁症持续了数百代。人口统计学和遗传恢复之间的时滞对最近出现瓶颈的种群的保护管理具有广泛的影响。
    A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths\' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.
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  • 文章类型: Journal Article
    以鼠疫为例,天花,艾滋病毒/艾滋病,本文主张纳入病原体进化史的好处,除了人群中可见的流行病高峰,我们对流行病实际上是流行病学现象的理解。大流行弧-将病原体作为大流行中的定义“演员”,从出现到地方扩散再到全球化——提供了一个框架,不仅能够汇集疾病表现的不同方面,而且能够汇集人类参与大流行进程的不同方面。病原体可能不同,但是疾病的出现和扩散有一些共同的模式来区分那些流行的疾病,分散在区域或全球人类社区中。允许追踪SARS-CoV-2等现代病原体的进化发展的相同基因组分析方法也使我们能够追踪过去的大流行。这些大流行弧线的重建带来了这些故事的新元素,恢复迄今为止被以欧洲为中心的叙事所忽视的地区和人口的经历。这扩大了传染病的全球历史,反过来,为重新实现真正的全球健康目标奠定了基础。
    Using the examples of plague, smallpox, and HIV/AIDS, the present essay argues for the benefits of incorporating the evolutionary histories of pathogens, beyond visible epidemic spikes within human populations, into our understanding of what pandemics actually are as epidemiological phenomena. The pandemic arc - which takes the pathogen as the defining \"actor\" in a pandemic, from emergence to local proliferation to globalization - offers a framework capable of bringing together disparate aspects not only of the manifestations of disease but also of human involvement in the pandemic process. Pathogens may differ, but there are common patterns in disease emergence and proliferation that distinguish those diseases that become pandemic, dispersed through human communities regionally or globally. The same methods of genomic analysis that allow tracking the evolutionary development of a modern pathogen such as SARS-CoV-2 also allow us to trace pandemics into the past. Reconstruction of these pandemic arcs brings new elements of these stories into view, recovering the experiences of regions and populations hitherto overlooked by Eurocentric narratives. This expanded global history of infectious diseases, in turn, lays a groundwork for reconceiving what ambitions a truly global health might aim for.
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  • 文章类型: Journal Article
    低基因组多样性通常表明种群规模小,并且被认为通过降低长期适应性而有害。1,2,3,4,5,6此外,小种群可能会促进同源物和远交抑郁症的基因流7,8,9,10,11,12,13这里,我们研究了栖息地可用性之间的联系,有效种群规模(Ne),通过从已灭绝的蓝色羚羊(Hippostragusleucophaeus)产生40倍核基因组来灭绝。历史上是非洲最南端相对较小的开普植物区特有的,人们认为14,15个种群在冰川-间冰期周期中扩张和收缩,跟踪合适的栖息地。16,17,18然而,我们发现Ne长期低,不受冰川周期的影响,这表明在公元1800年灭绝之前,基因组多样性低的持久性持续了几千年。缺乏近亲繁殖,伴随着高水平的基因净化,建议适应这种长期的低Ne,以及殖民时代的人类影响(例如,狩猎和景观改造),而不是长期的生态过程,是它灭绝的中心。系统学分析揭示了roan(H.马)和蓝色羚羊,以及在罗马和黑貂羚羊之间(H.尼日尔),大约在蓝色羚羊和黑貂羚羊的发散时间(~1.9Ma)。最后,我们确定了LYST和ASIP基因是蓝色羚羊同名蓝色毛皮颜色的候选基因。我们的结果修改了我们对基因组多样性和进化史之间相互作用的理解的许多方面,并为揭示这种灭绝物种的独特性状的遗传基础提供了资源。
    Low genomic diversity is generally indicative of small population size and is considered detrimental by decreasing long-term adaptability.1,2,3,4,5,6 Moreover, small population size may promote gene flow with congeners and outbreeding depression.7,8,9,10,11,12,13 Here, we examine the connection between habitat availability, effective population size (Ne), and extinction by generating a 40× nuclear genome from the extinct blue antelope (Hippotragus leucophaeus). Historically endemic to the relatively small Cape Floristic Region in southernmost Africa,14,15 populations were thought to have expanded and contracted across glacial-interglacial cycles, tracking suitable habitat.16,17,18 However, we found long-term low Ne, unaffected by glacial cycles, suggesting persistence with low genomic diversity for many millennia prior to extinction in ∼AD 1800. A lack of inbreeding, alongside high levels of genetic purging, suggests adaptation to this long-term low Ne and that human impacts during the colonial era (e.g., hunting and landscape transformation), rather than longer-term ecological processes, were central to its extinction. Phylogenomic analyses uncovered gene flow between roan (H. equinus) and blue antelope, as well as between roan and sable antelope (H. niger), approximately at the time of divergence of blue and sable antelope (∼1.9 Ma). Finally, we identified the LYST and ASIP genes as candidates for the eponymous bluish pelt color of the blue antelope. Our results revise numerous aspects of our understanding of the interplay between genomic diversity and evolutionary history and provide the resources for uncovering the genetic basis of this extinct species\' unique traits.
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  • 文章类型: Preprint
    古基因组学扩展了我们对人类进化史的认识。自2020年以来,古代DNA的研究增加了对重建最近过去的关注。然而,在人口统计学复杂性增加和遗传分化减少的情况下,古基因组学方法在回答历史和考古重要性问题方面的准确性仍然是一个悬而未决的问题。我们使用了两种模拟方法来评估常用方法的局限性和行为,qpAdm和f3-统计量,关于混合推断。第一个是基于从不同复杂性和配置的四个简单人口统计学模型模拟的分支长度数据。第二个,使用全基因组数据对59个种群组成的欧亚历史进行分析,这些数据是用古老的DNA条件(如SNP确定)进行修改的,数据缺失,和伪单倍体化。我们表明,在类似历史人口的条件下,qpAdm可以识别与它们密切相关的真实来源和群体的小候选集。然而,在典型的古代DNA条件下,qpAdm无法进一步区分它们,限制了其解决精细假设的效用。值得注意的是,我们发现,复杂的基因流历史通常会导致qpAdm性能的改善,并且在混合物权重的估计中没有偏差。我们为混合推断提供了一种启发式方法,该方法结合了混合权重估计和qpAdm模型的P值,和f3-统计信息,以增强区分多个似是而非的候选人的能力。最后,我们通过全基因组分支长度F2统计来强调qpAdm的未来潜力,证明了人口统计学推断的改进,这可以通过f统计量估计的改进来实现。
    Paleogenomics has expanded our knowledge of human evolutionary history. Since the 2020s, the study of ancient DNA has increased its focus on reconstructing the recent past. However, the accuracy of paleogenomic methods in answering questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation within the historical period remains an open question. We used two simulation approaches to evaluate the limitations and behavior of commonly used methods, qpAdm and the f3-statistic, on admixture inference. The first is based on branch-length data simulated from four simple demographic models of varying complexities and configurations. The second, an analysis of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudo-haploidization. We show that under conditions resembling historical populations, qpAdm can identify a small candidate set of true sources and populations closely related to them. However, in typical ancient DNA conditions, qpAdm is unable to further distinguish between them, limiting its utility for resolving fine-scaled hypotheses. Notably, we find that complex gene-flow histories generally lead to improvements in the performance of qpAdm and observe no bias in the estimation of admixture weights. We offer a heuristic for admixture inference that incorporates admixture weight estimate and P-values of qpAdm models, and f3-statistics to enhance the power to distinguish between multiple plausible candidates. Finally, we highlight the future potential of qpAdm through whole-genome branch-length f2-statistics, demonstrating the improved demographic inference that could be achieved with advancements in f-statistic estimations.
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  • 文章类型: Video-Audio Media
    背景:对来自考古人类和动物样本的古代口腔宏基因组的分析在很大程度上被来自现代和环境来源的污染DNA序列所混淆。现有的微生物源跟踪(MST)方法估计环境源的比例,但在古代宏基因组上表现不佳。我们开发了一种称为decOM的新方法,用于使用k-mer矩阵对古代和现代宏基因组样品进行微生物来源跟踪和分类。
    结果:我们分析了360个古代口腔,现代口述,沉积物/土壤和皮肤宏基因组,使用分层五折交叉验证。decOM高精度地估计了这些源环境在古代口腔宏基因组样本中的贡献,优于两种最先进的源跟踪方法,FEAST和mSourceTracker。
    结论:decOM是一种高精度的微生物源跟踪方法,适用于古代口腔宏基因组数据集。decOM方法是通用的,也可以适用于其他古代和现代类型的宏基因组的MST。我们预计decOM将成为古代宏基因组研究MST的宝贵工具。视频摘要。
    The analysis of ancient oral metagenomes from archaeological human and animal samples is largely confounded by contaminant DNA sequences from modern and environmental sources. Existing methods for Microbial Source Tracking (MST) estimate the proportions of environmental sources, but do not perform well on ancient metagenomes. We developed a novel method called decOM for Microbial Source Tracking and classification of ancient and modern metagenomic samples using k-mer matrices.
    We analysed a collection of 360 ancient oral, modern oral, sediment/soil and skin metagenomes, using stratified five-fold cross-validation. decOM estimates the contributions of these source environments in ancient oral metagenomic samples with high accuracy, outperforming two state-of-the-art methods for source tracking, FEAST and mSourceTracker.
    decOM is a high-accuracy microbial source tracking method, suitable for ancient oral metagenomic data sets. The decOM method is generic and could also be adapted for MST of other ancient and modern types of metagenomes. We anticipate that decOM will be a valuable tool for MST of ancient metagenomic studies. Video Abstract.
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  • 文章类型: Journal Article
    随着西罗马帝国在4世纪和5世纪加速崩溃,到达的“野蛮人”团体开始在衰落的(最终是前)帝国的边境省份建立新的社区。这是一个不仅在这些边境地区,而且在整个欧洲都发生了重大文化和政治变化的时代。1,2为了更好地了解匈牙利运动崩溃后这些关键边境地区之一的后罗马社区形成,我们从巴拉顿湖的三个5世纪墓地3,4,5的时间序列中产生了一组38个墓葬的新古基因组数据,匈牙利。我们采用了一种全面的采样方法来描述这些墓地的特征,以及先前发表的6世纪中叶遗址6的38个其他墓葬的数据,并与来自550多个古代个体的数据一起进行了分析。7,8,9,10,11,12,13,14,15,16,17,18,19所有四个这些地方墓葬社区的遗传多样性范围比迄今为止测序的欧洲古代时期广泛。尽管在墓葬习俗和人口学上有许多共性,我们发现两个位点之间的遗传祖先存在很大差异。我们检测到北欧基因流入巴拉顿湖地区的证据。此外,我们观察到,在5世纪遗传女性墓葬中,服饰文物与遗传血统之间存在统计学上的显着关联。我们的分析表明,即使在地方一级,早期中世纪社区的形成也是一个复杂的过程,由遗传异质性群体组成。
    As the collapse of the Western Roman Empire accelerated during the 4th and 5th centuries, arriving \"barbarian\" groups began to establish new communities in the border provinces of the declining (and eventually former) empire. This was a time of significant cultural and political change throughout not only these border regions but Europe as a whole.1,2 To better understand post-Roman community formation in one of these key frontier zones after the collapse of the Hunnic movement, we generated new paleogenomic data for a set of 38 burials from a time series of three 5th century cemeteries3,4,5 at Lake Balaton, Hungary. We utilized a comprehensive sampling approach to characterize these cemeteries along with data from 38 additional burials from a previously published mid-6th century site6 and analyzed them alongside data from over 550 penecontemporaneous individuals.7,8,9,10,11,12,13,14,15,16,17,18,19 The range of genetic diversity in all four of these local burial communities is extensive and wider ranging than penecontemporaneous Europeans sequenced to date. Despite many commonalities in burial customs and demography, we find that there were substantial differences in genetic ancestry between the sites. We detect evidence of northern European gene flow into the Lake Balaton region. Additionally, we observe a statistically significant association between dress artifacts and genetic ancestry among 5th century genetically female burials. Our analysis shows that the formation of early Medieval communities was a multifarious process even at a local level, consisting of genetically heterogeneous groups.
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  • 文章类型: Journal Article
    对过去的流行病和大流行的分析,无论是自发的还是人类起源的,可能会修改微生物群的物理史,并在我们对病原体属性如毒力的理解中创造一个时间背景,进化,传播和疾病动力学。高科技科学方法的数据似乎可靠,但是在处理遥远过去的事件时,他们的解释可能仍然有偏见。此类努力应根据其他认知资源进行调整,包括报告感兴趣事件的历史记载以及外来医学文化和术语中的参考;后者可能与当前实践不同。因此,“历史微生物学”应运而生。验证这些资源需要格外小心,因为这些可能容易受到关于事实和现象的解释的不同偏见;偏见部分是由于方法上的限制。
    细菌和病毒一直影响着人类。他们通过直接导致疾病或间接通过破坏农作物和威胁牲畜来做到这一点。通过研究过去的疾病事件,我们可以学到很多东西-例如,我们可以看到细菌和病毒如何随着时间的推移而变化,并预测它们在未来可能会如何变化。这些知识对于理解当前的疾病事件和预测未来的疾病事件可能很重要。在这次审查中,我们提出了“历史微生物学”的概念,这鼓励了科学家之间的合作,医生,历史学家和语言学家提供历史,我们对过去疾病的科学理解的语言和文化背景。
    The analysis of past epidemics and pandemics, either spontaneous or of human origin, may revise the physical history of microbiota and create a temporal context in our understanding regarding pathogen attributes like virulence, evolution, transmission and disease dynamics. The data of high-tech scientific methods seem reliable, but their interpretation may still be biased when tackling events of the distant past. Such endeavors should be adjusted to other cognitive resources including historical accounts reporting the events of interest and references in alien medical cultures and terminologies; the latter may contextualize them differently from current practices. Thus \'historical microbiology\' emerges. Validating such resources requires utmost care, as these may be susceptible to different biases regarding the interpretation of facts and phenomena; biases partly due to methodological limitations.
    Bacteria and viruses have always impacted humankind. They do this directly by causing illness or indirectly by destroying crops and threatening livestock. We can learn a lot by studying disease events of the past – for example, we can see how bacteria and viruses have changed over time and predict how they might change in the future. This knowledge could be important to understanding present disease events and predicting future ones. In this review, we propose the concept of \'historical microbiology’, which encourages collaboration between scientists, doctors, historians and linguists to provide historical, linguistic and cultural context to our scientific understanding of diseases of the past.
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  • 文章类型: Journal Article
    The results of studies in Quaternary geology, archeology, paleoanthropology and human genetics demonstrate that the ancestors of Native Americans arrived in mid-latitude North America mainly along the Pacific Northwest Coast, but had previously inhabited the Arctic and during the last glacial maximum were in a refugium in Beringia, a land bridge connecting Eurasia and North America. The gene pool of Native Americans is represented by unique haplogroups of mitochondrial DNA and the Y chromosome, the evolutionary age of which ranges from 13 to 22 thousand years. The results of a paleogenomic analysis also show that during the last glacial maximum Beringia was populated by human groups that had arisen as a result of interaction between the most ancient Upper Paleolithic populations of Northern Eurasia and newcomer groups from East Asia. Approximately 20 thousand years ago the Beringian populations began to form, and the duration of their existence in relative isolation is estimated at about 5 thousand years. Thus, the adaptation of the Beringians to the Arctic conditions could have taken several millennia. The adaptation of Amerindian ancestors to high latitudes and cold climates is supported by genomic data showing that adaptive genetic variants in Native Americans are associated with various metabolic pathways: melanin production processes in the skin, hair and eyes, the functioning of the cardiovascular system, energy metabolism and immune response characteristics. Meanwhile, the analysis of the existing hypotheses about the selection of some genetic variants in the Beringian ancestors of the Amerindians in connection with adaptation to the Arctic conditions (for example, in the FADS, ACTN3, EDAR genes) shows the ambiguity of the testing results, which may be due to the loss of some traces of the \"Beringian\" adaptation in the gene pools of modern Native Americans. The most optimal strategy for further research seems to be the search for adaptive variant.
    Результаты исследований в области четвертичной геологии, археологии, палеоантропологии и генетики человека показывают, что предки американских индейцев прибыли в средние широты Северной Америки главным образом по тихоокеанскому побережью. Но до этого они населяли Арктику и во время последнего ледникового максимума укрывались в рефугиуме на территории Берингии, соединявшей Евразию и Северную Америку. Генофонд американских индейцев представлен уникальными гаплогруппами митохондриальной ДНК и Y-хромосомы, эволюционный возраст которых составляет от 13 до 22 тыс. лет. Результаты анализа палеогеномных данных также свидетельствуют о том, что во время последнего ледникового максимума на территории Берингии сохранялись группы населения, возникшие в результате взаимодействия древнейшего верхнепалеолитического населения Северной Евразии и пришлых групп населения из Восточной Азии. Примерно 20 тыс. лет назад началось формирование популяций Берингии, а время их существования в относительной изоляции оценивается примерно в 5 тыс. лет. Таким образом, период адаптации берингийцев к условиям Арктики мог занять несколько тысячелетий. Адаптация предков америндов к высоким широтам и холодному климату подтверждается геномными данными, показавшими, что адаптивные генетические варианты у американских индейцев ассоциируются с различными метаболическими пу- тями: процессами продукции меланина в коже, волосах и глазах, функционированием сердечно-сосудистой системы, энергетическим обменом и особенностями иммунного ответа. Между тем анализ существующих гипотез об отборе некоторых генетических вариантов у берингийских предков америндов в связи с адаптацией к условиям Арктики (например, в генах FADS, ACTN3, EDAR) демонстрирует неоднозначность результа- тов проверки, что может быть связано с утратой некоторых следов «берингийской» адаптации в генофондах современных американских индейцев. Наиболее оптимальной стратегией дальнейших исследований представляется поиск адаптивных вариантов с помощью анализа палеогеномных данных с территории Берингии, однако таких генетических данных пока очень мало.
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  • 文章类型: Journal Article
    人类已经与病毒斗争了几千年。然而,直到二十世纪,才可能将疾病爆发的症状与特定的病毒病原体直接联系起来。随着基因组时代的到来和先进的分离方案的发展,测序,测序并分析来自不同人类遗骸的古代核酸,古代病毒的鉴定和表征变得可行。最近的研究提供了有关过去流行病的宝贵信息,并有可能检查有关某些病毒家族起源和进化的假设和推论。并行,对古代病毒的研究还揭示了它们在人类谱系进化中的重要性,以及它们在塑造人类历史上重大事件中的关键作用。在这次审查中,我们描述了用于研究古代病毒的策略,除了它们的局限性,并详细介绍了过去的病毒感染所揭示的人类历史。病毒学年度评论的预期最终在线发布日期,第10卷是2023年9月。请参阅http://www。annualreviews.org/page/journal/pubdates的订正估计数。
    Humans have battled viruses for millennia. However, directly linking the symptomatology of disease outbreaks to specific viral pathogens was not possible until the twentieth century. With the advent of the genomic era and the development of advanced protocols for isolation, sequencing, and analysis of ancient nucleic acids from diverse human remains, the identification and characterization of ancient viruses became feasible. Recent studies have provided invaluable information about past epidemics and made it possible to examine assumptions and inferences on the origin and evolution of certain viral families. In parallel, the study of ancient viruses also uncovered their importance in the evolution of the human lineage and their key roles in shaping major events in human history. In this review, we describe the strategies used for the study of ancient viruses, along with their limitations, and provide a detailed account of what past viral infections have revealed about human history.
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  • 文章类型: Journal Article
    Chauvet-Pont-d\'弧洞(Ardèche,法国)包含迄今为止记录的一些最古老的旧石器时代绘画,以及成千上万的已灭绝的洞穴熊的骨头,以及其他动物的一些遗骸和脚印。作为这个参考洞穴遗址的跨学科研究项目的一部分,我们分析了在深洞中收集的一种coprolite。AMS放射性碳测年来自coprolite的骨碎片的年龄为30,450±550RC年。BP(AAR-19656;36,150-34,000卡BP),类似于分配给旧石器时代的艺术品和来自同一洞穴区域的洞穴熊遗骸的年龄。使用高通量鸟枪DNA测序,我们展示了大量的犬科动物DNA和少量的来自已灭绝的洞穴熊的DNA。我们将样本解释为来自消耗了洞穴熊组织的犬科动物的粪便。大量的canidDNA使我们能够重建完整的canid线粒体基因组序列(平均覆盖率:83×),属于与同时代(〜35ka)比利时狼最密切相关的已灭绝线粒体狼谱系进化枝。对核基因组的分析对X染色体(2.4×)和常染色体(范围:2.3-3.2×)产生了相似的覆盖率,表明Chauvetcanid是雌性.比较该标本的核基因组与各种犬科动物的关系,我们发现它与灰狼的基因组比与其他野生犬科动物或狗的基因组更密切相关,尤其是来自欧洲和中东的狼基因组.我们得出的结论是,coprolite是来自已灭绝的狼血统中的动物的粪便。这只狼对洞穴熊的消耗可能解释了它对黑暗洞穴区域的入侵,并为主要洞穴遗址的古生态提供了新的启示。
    The Chauvet-Pont-d\'Arc Cave (Ardèche, France) contains some of the oldest Paleolithic paintings recorded to date, as well as thousands of bones of the extinct cave bear, and some remains and footprints of other animals. As part of the interdisciplinary research project devoted to this reference cave site, we analyzed a coprolite collected within the deep cave. AMS radiocarbon dating of bone fragments from the coprolite yielded an age of 30,450 ± 550 RC yr. BP (AAR-19656; 36,150-34,000 cal BP), similar to ages assigned to Paleolithic artwork and cave bear remains from the same cave sector. Using high-throughput shotgun DNA sequencing, we demonstrated a high abundance of canid DNA and lesser amounts of DNA from the extinct cave bear. We interpret the sample as feces from a canid that had consumed cave bear tissue. The high amount of canid DNA allowed us to reconstruct a complete canid mitochondrial genome sequence (average coverage: 83×) belonging to a deeply divergent clade of extinct mitochondrial wolf lineages that are most closely related to coeval (~35 ka) Belgian wolves. Analysis of the nuclear genome yielded a similar coverage for the X chromosome (2.4×) and the autosomes (range: 2.3-3.2×), indicating that the Chauvet canid was a female. Comparing the relationship of the nuclear genome of this specimen with that of a variety of canids, we found it more closely related to gray wolves\' genomes than to other wild canid or dog genomes, especially wolf genomes from Europe and the Middle East. We conclude that the coprolite is feces from an animal within an extinct wolf lineage. The consumption of cave bear by this wolf likely explains its intrusion into the dark cave sectors and sheds new light on the paleoecology of a major cave site.
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