The Great Tit HapMap Project

大多数对科学感兴趣的人都知道，过去十年见证了基因组学工具和技术的巨大进步。令人兴奋的是，这些新技术不仅限于人类或果蝇和酵母等经典模型生物，而且现在可以应用于生态学家长期以来感兴趣但迄今为止缺乏遗传学工具的生物。我们利用所谓的下一代测序提供的机会来开发大山雀的基因组学资源。大山雀（Parus Major）是研究最广泛的无脊椎动物之一，因为它们很常见并且很容易在人造巢箱中繁殖。因此，欧洲各地对大山雀种群进行了许多长期研究，其中一些研究已经持续了 50 多年，包括数万只鸟类个体的数据。这些长期数据集为研究重要的生态问题提供了丰富的资源，例如：生物体如何适应气候变化、生物体如何分配资源进行繁殖和其他活动、物种如何在自然选择中进化。利用从欧洲研究委员会 (ERC) 和荷兰政府获得的资金，我们已经开始绘制两个研究最深入的种群（英国的 Wytham Woods 和荷兰的 de Hoge Veluwe）中负责生命史和形态特征变异的基因图谱。通过英国-荷兰合作，我们汇集了基因组学资源，并开发了一种称为 SNP 芯片的工具，该工具使我们能够在每个研究人群中键入 9000 多个遗传标记。目前，我们已使用该芯片对 2000 多只荷兰鸟类和 2700 多只英国鸟类进行了分型。在本提案中，我们请求资金进一步培育 16 个大山雀种群（每个种群 50 只）。我们为什么要这样做？主要原因是，通过在许多不同种群中输入相同的遗传标记，我们可以表征整个物种范围内的遗传变异，以便更多地了解物种的进化历史。这种性质的项目有时被称为 HapMap 项目，因为它们涉及沿染色体连接的标记（HAPlotypes）的映射。最著名的 HapMap 项目是在人类身上进行的，它使人们深入了解我们的物种在从非洲迁徙后如何在世界上殖民、不同种群之间如何相互关联，以及基因如何使我们能够适应环境等。不同的环境条件、新的挑战，如新出现的疾病、饮食的变化等。通过开展大山雀单体型图项目，我们可以在这个广泛研究的生态模式生物中解决类似的问题。这也意味着我们可以扩展 Wytham 和 de Hoge Veluwe 种群的发现，以提出有关进化遗传学的基本问题。例如：相同的基因可以解释不同人群的适应吗？一个群体中产生的有益基因是否会迅速传播到其他群体？解释种群内变异的基因是否也可以解释种群之间的差异？种群之间的迁移在维持遗传多样性方面发挥着重要作用吗？这种基因流是否有助于或阻碍局部适应？也许没有其他脊椎动物拥有多个长期生态数据集和如此广泛的基因组学资源。因此，大山雀是进行第一个“自然种群”单体型图项目的理想生物。

Most people interested in science are aware that the last decade has witnessed dramatic advances in genomics tools and techniques.Excitingly, these new technologies are not limited to humans or classical model organisms like fruitflies and yeasts, but can now be applied to organisms which have long interested ecologists but which, until now, lacked genetics tools. We have taken advantage of the opportunities afforded by so-called next generation sequencing to develop genomics resources for the great tit.Great tits (Parus major) are one of the most widely studied invertebrates because they are common and readily breed in artifical nest boxes. As a result a number of long term studies of great tit populations have been conducted across Europe, some of which have been ongoing for more than 50 years and include data on tens of thousands of individual birds.These long-term datasets are rich resources for studying important ecological questions such as: How organisms adapt to climate change, How organisms allocate resources to breeding and other activities, How species evolve in the face of natural selection. Using funds won from the European Research Council (ERC) and the Netherlands government, we have begun to map genes responsible for variation in life history and morphological traits in two of the most intensively studied populations - at Wytham Woods in the UK and de Hoge Veluwe in The Netherlands. By working as a UK-Dutch collaboration we have pooled genomics resources and developed a tool called a SNP chip which allows us to type more than 9000 genetic markers in each of our study populations. We have now typed more than 2000 Dutch birds and 2700 UK birds with this chip. In this proposal, we request funds to type a further 16 great tit populations (50 birds per population). Why do we want to do this? The main reason is that by typing the same genetic markers in lots of different populations we can characterise genetic variation across the entire species range in order to learn more about the species evolutionary history. Projects of this nature are sometimes called HapMap Projects because they involve the mapping of markers linked along a chromosome (HAPlotypes). The best known HapMap project has been conducted in humans and has led to great insight into how our species colonised the world after migrating from Africa, how different populations are related to each other, and how genes have enabled us to adapt to e.g. different environmental conditions, novel challenges such as emerging diseases, changes in diet etc. By carrying out a Great Tit HapMap Project we can address similar questions in this widely studied ecological model organism. This also means we can extend the findings from the Wytham and de Hoge Veluwe populations to ask fundamental questions about evolutionary genetics. For example: Do the same genes explain adaptation in different populations? Do beneficial genes that arise in one population rapidly spread to other populations? Do the genes that explain variation within a population also explain differences between populations? Does migration between populations play a major role in maintaining genetic diversity? Does this gene flow help or hinder local adaptation?There is perhaps no other vertebrate for which multiple long-term ecological datasets and such extensive genomics resources are available. Therefore, the great tit is an ideal organism in which to perform the first 'natural population' HapMap Project.