Evolutionary dynamics of the natural Drosophila microbiome

地球上所有已知的生物都与微生物有关。病原微生物可以对其宿主施加强大的选择压力。因此，参与病原体防御的基因经常参与与病原体的进化军备竞赛，因此是进化最快的基因之一。另一方面，微生物促进了它们的后生动物宿主的大量重大适应性进化创新。然而，旨在了解生物体如何适应环境的研究往往忽视了微生物组在适应过程中的作用。D. melanogaster生活在微生物丰富的环境中，腐烂的水果。它的表型和适应度强烈依赖于微生物组。这表明黑腹龙是在自然选择下进化出控制其相关微生物群的机制。这意味着要塑造微生物群，使其受益。为了使选择压力导致宿主控制的适应性进化，被选择的性状必须是可变的，并且必须具有可遗传的遗传成分。我们假设，在唯一与进化相关的环境中，在自然条件下，(i)黑腹d.m anogaster相关的微生物组是不同的，（ii）这种变异的一个组成部分取决于宿主的基因型，（iii）基础基因座的变异是由自然选择形成的。我们在包括两个主要项目部分的工作计划中解决这些假设。在第一部分中，我们将利用欧洲果蝇种群基因组学联盟（DrosEU）的资源，利用在欧洲收集的1000个样本进行微生物组基因组全关联研究（mGWAS）。这将使我们能够量化宿主遗传因素对微生物组变异的贡献，并确定基础位点（mQTL）。果蝇特别适合这样的研究，因为它具有(i)低水平的连锁不平衡，可以将mqtl精确到SNP水平，（ii）低水平的种群结构可能干扰GWAS， （iii）相对简单的微生物组，有助于成本效益和详细的评估，（iv）几乎无与伦比的遗传可追溯性，用于mGWAS结果的实验评估。在第二步中，我们将在进化框架中分析mGWAS结果，以了解在基因组水平上形成微生物组相互作用位点变异的最终力量。因此，我们将使用最先进的群体基因组方法，包括但不限于新的测试来检测复杂性状的多基因选择。除了分析整个欧洲潜在的不同选择压力外，我们还将利用来自果蝇祖先范围的公开可获得的种群遗传数据来测试来自非洲的扩张和温带气候的殖民化是否伴随着微生物组相互作用位点的选择。

All known organisms on earth are associated with microorganisms. Pathogenic microorganisms can exert strong selection pressures on their hosts. As a consequence genes involved in pathogen defense often take part in an evolutionary arms race with pathogens, and hence are among the fastest evolving genes. On the other hand, microbes have facilitated a plethora of major adaptive evolutionary innovations of their metazoan hosts. Nonetheless, studies that aim at understanding how organisms adapt to the environment often neglect the role of the microbiome in the adaptive process. D. melanogaster lives in a microbe rich environment, rotting fruit. Its phenotype and fitness are strongly microbiome dependent. This suggests that D. melanogaster is under selection to evolve mechanisms to control its associated microbiome. This means to shape the microbiome for its benefit. In order for selection pressure to result in adaptive evolution of host control, the selected traits have to be variable and have to have a heritable genetic component. We hypothesize that in the only evolutionary relevant setting, under natural conditions, (i) the D. melanogaster associated microbiome varies, (ii) there is a component of this variation that depends on host genotype, (iii) the variation in the underlying loci is shaped by natural selection. We address these hypotheses in a work program including two major project parts. In the first part, we will perform a microbiome Genome Wide Association Study (mGWAS) using 1000 samples collected in Europe, leveraging the resources of the European Drosophila Population Genomics Consortium (DrosEU). This will allow us to quantify the contribution of host genetic factors to microbiome variation and to identify the underpinning loci (mQTL). Drosophila is exceptionally well suited for such a study because it has (i) low levels of linkage disequilibrium that allows to pinpoint mQTLs to the SNP level, (ii) low levels of populations structure that could interfere with GWAS, (iii) a relatively simple microbiome that facilitates a cost effective and detailed assessment, (iv) an almost unrivaled genetic tractability for experimental assessment of mGWAS results. In a second step, we will analyze the mGWAS results in an evolutionary framework, to understand the ultimate forces that shape the variation at microbiome-interacting loci on a genomic level. Therefore, we will use state of the art population genomic methods including, but not limited to novel tests to detect polygenic selection on complex traits. In addition to analyzing potentially varying selective pressures across Europe, we will leverage publicly available population genetic data from the ancestral range of flies to test whether the expansion from Africa and colonization of temperate climates was accompanied by selection on microbiome interacting loci.