A transmissible cancer shifts from emergence to endemism in Tasmanian devils
A transmissible cancer shifts from emergence to endemism in Tasmanian devils
复制标题
塔斯马尼亚袋獾中的一种传染性癌症从出现转变为地方流行
DOI：
10.1126/science.abb9772
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发表时间：
2020
期刊：
影响因子：
56.9
通讯作者：
Taylor, Robyn L.
中科院分区：
文献类型：
--
作者：
Patton, Austin H.;Lawrance, Matthew F.;Margres, Mark J.;Kozakiewicz, Christopher P.;Hamede, Rodrigo;Ruiz-Aravena, Manuel;Hamilton, David G.;Comte, Sebastien;Ricci, Lauren E.;Taylor, Robyn L.
引言新出现的传染病是对人类健康和生物多样性的最大威胁之一。系统动力学是推断流行病学参数以指导干预策略的有效工具，特别是对于严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）等人类病毒。然而，生物动力学分析在历史上仅限于研究快速进化的病毒，在极少数情况下，细菌。尽管如此，非病毒性病原体的生物学动力学的应用具有巨大的潜力，如预测疾病传播和通知野生动物diseases.We的管理进行了魔鬼面部肿瘤病（DFTD），一种传染性癌症，已蔓延到几乎整个塔斯马尼亚魔鬼的地理范围和灭绝的威胁物种的生物学动力学分析。DFTD在常见的社会交往中通过咬伤作为同种异体移植物传播，易感性几乎是普遍的，病死率接近100%。我们研究的目的是（i）描述DFTD的地理分布，（ii）确定是否有不同的循环肿瘤谱系，（iii）量化谱系之间的传播率。原理原则上，通过仔细询问基因，确定那些可测量的进化，可以很容易地将免疫动力学扩展到具有大基因组的缓慢进化的病原体的研究。通过测试单个基因的时钟信号，这些基因可以用于生物动力学分析。我们在DFTD基因组中筛选了超过11，000个基因，确定了28个表现出强烈的时钟样信号，并对大于细菌的基因组进行了首次动态分析。我们在这里证明，相反的实地观察，DFTD传播全方位的整个流行病，几乎没有信号的肿瘤谱系的地理结构在塔斯马尼亚州。尽管预测魔鬼会灭绝，但我们发现有效繁殖数（RE）（疾病传播速度的总结）在DFTD最初的流行传播后急剧下降。具体而言，在1996年发现DFTD后不久，RE达到约3.5的高峰，现在在两种现存肿瘤谱系中约为1。这与从紧急到特有的转变是一致的。除了一个单一的基因，我们发现几乎没有证据表明收敛的分子进化肿瘤lineage. CONCLUSION之间，我们已经证明，肿瘤动力学几乎可以应用于任何病原体。在这样做的过程中，我们表明，通过仔细询问病原体基因组，可以确定一组可测量的进化基因，以表征具有大基因组的非病毒病原体的流行病学动态。通过将这种方法应用于DFTD，我们已经表明，这种疾病似乎正在从出现过渡到特有性。与最近的模型一致，我们的推论RE ~1预测魔鬼和DFTD共存比魔鬼灭绝更可能的结果。因此，我们的研究结果对标志性塔斯马尼亚恶魔的持续生存持谨慎乐观态度，但强调需要基于进化的保护管理来确保它们的持续存在。塔斯马尼亚恶魔及其传染性癌症健康（上）和感染DFTD（下）的塔斯马尼亚恶魔。照片：大卫G.汉密尔顿（上），亚历山德拉K. Fraik（底部）。
INTRODUCTIONEmerging infectious diseases pose one of the greatest threats to human health and biodiversity. Phylodynamics is an effective tool for inferring epidemiological parameters to guide intervention strategies, particularly for human viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, phylodynamic analysis has historically been limited to the study of rapidly evolving viruses and, in rare cases, bacteria. Nonetheless, application of phylodynamics to nonviral pathogens has immense potential, such as for predicting disease spread and informing the management of wildlife diseases.We conducted a phylodynamics analysis of devil facial tumor disease (DFTD), a transmissible cancer that has spread across nearly the entire geographic range of Tasmanian devils and threatens the species with extinction. DFTD is transmitted as an allograft through biting during common social interactions, susceptibility is nearly universal, and case fatality rates approach 100%. The goals of our study were to (i) characterize the geographic spread of DFTD, (ii) identify whether there are different circulating tumor lineages, and (iii) quantify rates of transmission among lineages.RATIONALEIn principle, phylodynamics should be readily extended to the study of slowly evolving pathogens with large genomes through careful interrogation of genes to identify those that are measurably evolving. By testing individual genes for a clocklike signal, these genes may then be used for phylodynamic analysis. We demonstrate this proof of concept in DFTD.RESULTSWe screened >11,000 genes across the DFTD genome, identifying 28 that exhibited a strong, clocklike signal, and performed the first phylodynamic analysis of a genome larger than a bacterium. We demonstrate here, contrary to field observations, that DFTD spread omnidirectionally throughout the epizootic, leaving little signal of geographic structuring of tumor lineages across Tasmania. Despite predictions of devil extinction, we found that the effective reproduction number (RE), a summary of the rate at which disease spreads, has declined precipitously after the initial epidemic spread of DFTD. Specifically,REpeaked at a high of ~3.5 shortly after the discovery of DFTD in 1996 and is now ~1 in both extant tumor lineages. This is consistent with a shift from emergence to endemism. Except for a single gene, we found little evidence for convergent molecular evolution among tumor lineages.CONCLUSIONWe have demonstrated that phylodynamics can be applied to virtually any pathogen. In doing so, we show that through careful interrogation of the pathogen genome, a measurably evolving set of genes can be identified to characterize epidemiological dynamics of nonviral pathogens with large genomes. By applying this approach to DFTD, we have shown that the disease appears to be transitioning from emergence to endemism. Consistent with recent models, our inference thatRE~1 predicts that coexistence between devils and DFTD is a more likely outcome than devil extinction. Therefore, our findings present cautious optimism for the continued survival of the iconic Tasmanian devil but emphasize the need for evolutionarily informed conservation management to ensure their persistence.Tasmanian devils and their transmissible cancerHealthy (top) and DFTD-infected (bottom) Tasmanian devils.Photos: David G. Hamilton (top), Alexandra K. Fraik (bottom).
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