The Great Tit HapMap Project

大多数对科学感兴趣的人都知道，在过去的十年里，基因组学工具和技术取得了巨大的进步。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式生物，而且现在可以应用于生态学家长期以来感兴趣的生物，但到目前为止，这些生物缺乏遗传学工具。我们利用所谓的下一代测序提供的机会为大山雀开发基因组学资源。大山雀是研究最广泛的无脊椎动物之一，因为它们很常见，很容易在人工巢穴箱中繁殖。因此，欧洲各地对大山雀种群进行了许多长期研究，其中一些研究已经进行了50多年，包括数万只鸟类的数据。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，如：生物如何适应气候变化，生物如何为繁殖和其他活动分配资源，物种如何在自然选择面前进化。利用从欧洲研究理事会(ERC)和荷兰政府获得的资金，我们已经开始在英国的Wytham Wood和荷兰的De Hoge Veluwe这两个研究最深入的种群中绘制导致生活史和形态特征变化的基因图谱。通过英国和荷兰的合作，我们汇集了基因组资源，并开发了一种名为SNP芯片的工具，使我们能够在每个研究人群中键入9000多个遗传标记。我们现在已经用这个芯片打出了2000多只荷兰鸟和2700多只英国鸟。在这项提案中，我们要求资金再对16个大山雀种群进行分型(每个种群50只鸟)。我们为什么要这样做？主要原因是，通过在许多不同的种群中键入相同的遗传标记，我们可以表征整个物种范围的遗传变异，以便更多地了解物种的进化史。这种性质的项目有时被称为HapMap项目，因为它们涉及沿着染色体(单倍型)链接的标记的作图。最著名的HapMap项目已经在人类身上进行，并导致我们深入了解我们的物种在从非洲移民后如何殖民世界，不同的种群如何相互关联，以及基因如何使我们能够适应不同的环境条件、新出现的疾病、饮食变化等新挑战。通过实施大山雀HapMap项目，我们可以在这个被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威瑟姆和德霍格维卢韦种群的发现，以提出关于进化遗传学的基本问题。例如：相同的基因能解释不同种群的适应吗？在一个种群中出现的有益基因会迅速传播到其他种群吗？解释种群内部差异的基因是否也解释了种群之间的差异？种群间的迁徙在维持遗传多样性方面发挥了重要作用吗？这种基因流动是有助于还是阻碍局部适应？可能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，大山雀是执行第一个‘自然种群’HapMap计划的理想有机体。

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.