The spatial epidemiology and molecular evolution of panzootic amphibian chytridiomycosis

现代两栖动物的灭绝速度远远超过任何其他脊椎动物，包括哺乳动物和鸟类，近三分之一的两栖动物物种受到威胁。为什么两栖动物以如此快的速度灭绝，这个问题困扰了科学家三十年。当在中美洲和澳大利亚工作的科学家注意到两栖动物生物多样性的下降正在以波浪式的方式从一个点源传播时，这个谜团的线索就出现了。这些下降的模式是由一种新出现的传染病引起的，1997年研究人员发现了这种真菌病原体，并将其命名为Batrachochytrium dendrobatim（Bd）。从那时起，我们的研究一直集中在找出真菌在哪里，它正在传播到哪里，以及它对两栖动物生物多样性的影响。我们在www.bd-maps.net上制作了一个地图工具，这表明Bd发生在所有大陆的两栖动物身上。然而，并非所有感染Bd的物种和种群都会死亡，这向我们表明可能存在不止一种Bd菌株（或谱系），并且这些菌株（或谱系）的破坏性并不相同。当我们使用新的全基因组测序技术对来自世界各地的Bd分离株进行测序时，证实了这一点。我们发现了Bd的三个谱系，并表明其中只有一个是负责大规模死亡和物种衰退。我们将这一谱系命名为BdGPL，即“Bd全球泛动物谱系”，并表明它发生在非洲、欧洲、澳大利亚和美洲。我们将通过对非洲和欧洲广泛分布的Bd分离株的基因组进行测序，并对病原体被引入新环境的影响进行精细研究，来调查这种“Bd出非洲”的假设。我们的项目将通过在大陆水平上表征Bd的基因组多样性来研究广泛和精细的过程，但也将重点放在非洲，比利牛斯山脉，阿尔卑斯山和英国的精细尺度进化模式上。我们将把这些基因组方法与实验方法结合起来，以确定入侵性“爆发”谱系是否由于自然选择作用的加速进化而改变了它们的毒力和传染性。在这里，我们的期望是，与原始地理背景中的祖先谱系相比，正在适应新环境和宿主的爆发谱系将具有更高的毒力和传播率。这些实验不仅可以让我们在确定这些感染的地理来源时增加确定性，而且还可以让我们评估为什么BdGPL比其他Bd谱系更具毒性和传播性。更广泛地说，我们的研究将告知我们新病原体对未感染环境构成的风险。目前，我们看到许多新出现的致病真菌对森林、蝙蝠和青蛙造成了不可估量的破坏。也许在这些疾病的出现背后存在着共同的过程--不仅是受感染商品的全球贸易，还有真菌特有的基因组水平的过程？在生物多样性进一步丧失之前，这里所描述的项目是回答这些重要问题的关键。

Modern-day amphibians are known to be suffering rates of extinction that far exceed any other class of vertebrates, including those experienced by mammals and birds, and nearly one third of amphibian species are threatened. The question of why amphibians are going extinct at these accelerated rates has puzzled scientists for three decades. A clue to the mystery came about when scientists working in Central America and Australia noted that the declines in amphibian biodiversity were spreading in a wave-like manner, from a point source. These patterns of decline were caused by an emerging infectious disease, and in 1997 researchers discovered the fungal pathogen and named it Batrachochytrium dendrobatidis (Bd). Since then, our research has been focused on finding out where the fungus is, where it is spreading to and what its effect is on amphibian biodiversity. We have made a mapping tool at www.bd-maps.net and this has shown that Bd occurs on all continents with amphibians. However, not all species and populations infected with Bd die, suggesting to us that there may be more than one strain (or lineage) of Bd and that these are not all equally destructive. Confirmation of this came when we used new whole genome sequencing technology to sequence isolates of Bd from around the world. We discovered three lineages of Bd, and showed that only one of them is responsible for mass mortalities and species declines. We named this lineage BdGPL for 'Bd Global Panzootic Lineage' and showed that it occured in Africa, Europe, Australia and America.Currently, several lines of argument suggest that BdGPL evolved in Africa. We will investigate this 'Bd Out-of-Africa' hypothesis by sequencing the genomes of Bd isolates widely across Africa and Europe, and undertaking fine-scale studies of the pathogens impact where it has been introduced into new environments. Our project will investigate both broad- and fine-scale processes, by characterising the genome diversity of Bd at the continental-level, but also focusing on fine-scale evolutionary patterns in Africa, the Pyrenees, the Alps and the UK. We will twin these genomic approaches with experimental approaches in order to determine whether invasive 'outbreak' lineages have altered their virulence and infectivity owing to accelerated evolution by the action of natural selection. Here, our expectation is that outbreak lineages that are adapting to new environments and hosts will have increased virulence and transmission rates when compared against the ancestral lineage in its original geographic background. These experiments will not only give us added certainty when determining the geographic origins of these infections, but will also allow us to assess why BdGPL is so much more virulent, and transmittable, than the other lineages of Bd.More widely, our research will inform us about the risk that new pathogens pose to uninfected environments. Currently, we are seeing many emerging pathogenic fungi causing untold destruction to forests, bats and frogs. Perhaps there are common processes that underlie these emergences of disease - not only global trade in infected goods but also genome-level processes that are unique to fungi? Projects such as that described here hold the key to answering these important questions before losses of biodiversity increase further.