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，这些新技术不仅局限于人类或经典的模式生物，如果蝇和酵母，而且现在可以应用于生态学家长期感兴趣的生物，但直到现在，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，而且很容易在人工巢箱中繁殖。因此，人们在欧洲各地对大山雀的种群进行了大量的长期研究，其中一些研究已经进行了50多年，其中包括成千上万只鸟的数据。这些长期数据集是研究重要生态问题的丰富资源，如：生物如何适应气候变化，生物如何分配资源用于繁殖和其他活动，物种如何在自然选择中进化。利用欧洲研究委员会（ERC）和荷兰政府提供的资金，我们已经开始在英国威瑟姆森林（Wytham Woods）和荷兰de Hoge Veluwe这两个研究最深入的种群中绘制与生活史和形态特征变异有关的基因图谱。通过与英国和荷兰的合作，我们汇集了基因组学资源，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输入9000多个遗传标记。我们现在已经用这个芯片输入了2000多只荷兰鸟类和2700多只英国鸟类。在这一提案中，我们要求资金进一步分类16个大山雀种群（每个种群50只鸟）。我们为什么要这么做？主要原因是，通过在许多不同的种群中对相同的遗传标记进行分类，我们可以描述整个物种范围内的遗传变异，从而更多地了解物种的进化史。这种性质的项目有时被称为单体型图项目，因为它们涉及到沿染色体连接的标记的绘制（单体型）。最著名的HapMap项目是在人类身上进行的，它让我们对人类如何从非洲迁移到世界上有了深刻的了解，不同的种群是如何相互关联的，以及基因如何使我们适应不同的环境条件，新出现的疾病等新挑战，饮食变化等。通过开展大山雀单体型图项目，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从威瑟姆和德霍格韦卢威种群的发现，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性吗？在一个种群中产生的有益基因会迅速传播到其他种群吗？解释种群内变异的基因是否也能解释种群间的差异？种群间的迁移是否在维持遗传多样性方面发挥了重要作用？这种基因流动是帮助还是阻碍了局部适应？也许没有其他脊椎动物有如此多的长期生态数据集和如此广泛的基因组资源。因此，大山雀是执行第一个“自然种群”HapMap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.