A lifetime of attrition: post-genomic analyses of ecological and evolutionary processes in nematode - vertebrate systems.

几乎每一种陆地、淡水和海洋脊椎动物都被线虫（蛔虫）寄生。线虫感染在宿主一生中表现出持续感染和再感染，对感染强度有强烈的性别、年龄和季节影响。因此，这些寄生虫构成了脊椎动物环境的重要组成部分，影响着个体的适应性和种群的动态。现在有一个及时的机会，应用基因组学的新方法来探索自然环境中脊椎动物-线虫相互作用的生态和进化后果。这类工作前景广阔，但将基因组学从实验台扩展到自然种群也面临着重大挑战。特别是，个体之间的差异使得自然种群研究如此重要，也使得一些基因组学方法难以应用，例如高通量基因表达（微阵列）分析。我们对这些挑战的回应是建立一个以三种特征良好的脊椎动物-线虫系统为基础的联盟，Soay羊和Teladorsagia皮环虫，红松鸡和柔顺毛线虫，棕色老鼠和圆形线虫。我们将使用一系列方法，从模拟野生情况的实验室实验中的微阵列研究，到对生活在野生种群中的个体进行实验操作的微阵列研究。因此，我们希望相互学习，并向研究界展示，这些新方法在多大程度上可以应用于原地的自然种群。在这个过程中，我们希望培养一批训练有素的工人，他们具备在英国更广泛地发展这一领域的技能。在联盟内的工作将探索一系列相关问题，结合起来，使我们能够解决两个广泛的目标，这对于促进我们对宿主-寄生虫生态学和进化的理解至关重要：(1)剖析和量化宿主-寄生虫相互作用的遗传基础与宿主和寄生虫的种群生物学之间的联系。感染是一个作用于个人但影响群体动态的过程；通过感染对个体生长、生存和繁殖的影响。同样，种群的密度也会影响个体之间对食物或配偶的竞争程度，从而影响个体的状况及其对感染的易感性。现在的关键挑战是了解个体感染过程如何影响宿主和寄生虫的种群生物学，以及如何受到宿主和寄生虫种群生物学的影响。(2)研究寄主和寄生虫种群遗传多样性的起源和维持。在一个种群中，个体宿主对感染的易感性表现出遗传差异。同样，寄生线虫种群在遗传上是可变的，这对感染的持续存在和传播造成了影响。现在需要解决的关键挑战是确定脊椎动物和线虫基因组中通过两种拮抗剂之间的持续相互作用来维持遗传多样性的区域，这种遗传多样性的后果以及维持这种多样性的选择过程。

Virtually every species of terrestrial, freshwater and marine vertebrate is parasitized by nematodes (roundworms). Nematode infections exhibit persistent infection and re-infection throughout the life of a host, with strong sex, age and season effects on intensities of infection. These parasites therefore constitute an important component of the environment of vertebrates and affect the fitness of individuals and the dynamics of populations. There is now a timely opportunity to apply new methods from genomics to explore the ecological and evolutionary consequences of vertebrate-nematode interactions in the natural environment. Such work holds great promise but extending genomics from the bench-top to natural populations also presents significant challenges. In particular, the variation between individuals that makes research in natural populations so important also makes it difficult to apply some genomics methods, such as high throughput gene expression (microarray) analyses. Our response to these challenges is to build a consortium based around three well-characterised vertebrate - nematode systems, the Soay sheep and Teladorsagia circumcincta, the red grouse and Trichostrongylus tenuis and the brown rat and Strongyloides ratti. We will use a series of approaches ranging from microarray studies within laboratory experiments that mimic the wild situation, through to microarray studies on individuals living in wild populations subject to experimental manipulations. As a result, we hope to learn from each other, and demonstrate to the research community, just how far these new methodologies can be applied to natural populations in situ. In the process, we expect to generate a trained group of workers with the skills to develop the field more widely in the UK. Work within the consortium will explore a set of related questions that, in combination, allow us to address two broad objectives that are crucial to advancing our understanding of host-parasite ecology and evolution: (1) To dissect and quantify the link between the genetic basis of host-parasite interactions and the population biology of hosts and parasites. Infection is a process that acts on individuals but impacts on the dynamics of populations; through the effects of infection on the growth, survival and reproduction of individuals. Equally, the density of a population will impact on the level of competition between individuals for food or mates and consequently on the condition of individuals and their susceptibility to infection. The key challenge now is to understand how individual processes of infection influence, and are influenced by, the population biology of hosts and parasites. (2) To examine the origins and maintenance of genetic diversity in host and parasite populations. Within a population, individual hosts exhibit genetic differences in their susceptibility to infection. Equally, populations of parasitic nematodes are genetically variable with consequences for the persistence and transmission of infection. The key challenges to be addressed now are to identify regions of vertebrate and nematode genomes where genetic diversity is maintained through the continued interaction between both antagonists, the consequences of this genetic diversity and the selective processes by which this diversity is maintained.