Assessing the role of host-microbe interaction in adaptation using Drosophila melanogaster and acetic acid bacteria as a model

尽管与宿主相关的微生物是适应的重要促进者，这一点越来越明显，但目前大多数旨在了解生物如何适应环境的研究仍然集中在宿主有机体上。我们的目标是通过评估宿主和微生物如何在适应中相互作用来拓宽这一视角，并以黑腹葡萄球菌和醋酸菌(AAB)为模型。D.黑腹胡蜂和AAB生活在这样的环境中：主要食物来源成熟的水果是短暂的，往往是片状的，含糖量高，氨基酸含量低。在实验室氨基酸贫乏的条件下，AAB可促进果蝇生长，缩短发育时间达10天。因为我们和其他人已经证明AAB通常与野生捕获的黑腹果蝇有关，似乎有理由认为它们也可以在自然条件下对苍蝇的健康和适应做出贡献。因此，结合和运输促进生长的AAB到新的食物来源和产卵地点应该是适合苍蝇的。与此同时，固定细菌可以受益于苍蝇在一种短暂而零星的资源上的传播。因此，有利于将黑腹果蝇与有益的AAB联系在一起的基因变异可以促进双方的适应，并应该在细菌和果蝇中显示出积极选择的足迹。拟议的研究将集中在微生物共生体方面，而到目前为止，微生物共生体受到的关注较少。我们将研究宿主介导的扩散的机制和分子基础，以及它们如何有助于苍蝇的健康。因此，我们将(I)测量苍蝇介导的细菌扩散，并将这一特征与泛基因组广泛关联研究中的细菌基因和变体联系起来，(Ii)通过转录图谱寻找主要有益细菌与果蝇相互作用时活跃的基因，以及(Iii)对在泛基因组广泛关联研究中发现的基因和变体以及转录图谱进行进化分析。最后，将使用基因敲除技术和现有的大陆规模微生物群落数据来分析来自PAN-GWA和转录图谱的基因的细菌传播和苍蝇健康相关功能，以了解它们在环境适应中的功能。虽然其他研究主要是研究果蝇与微生物的相互作用，主要集中在实验室衍生的细菌或在自然条件下很少遇到苍蝇的细菌，但我们将重点放在从野生捕获的黑腹果蝇中分离出来的细菌，因此可能与进化相关。使用果蝇-AAB模型，我们可以利用寄主的大种群基因组和遗传资源，以及用于微生物的全套基因工程工具。这项拟议的研究有能力改变我们对有机体如何适应的理解。

Although it is becoming more and more evident that host associated microbes are important facilitators of adaptation, most studies today that aim at understanding how organisms adapt to their environment still focus on the host organism alone. We aim at broadening this perspective by assessing how hosts and microbes interact in adaptation using D. melanogaster and acetic acid bacteria (AAB) as a model. D. melanogaster and AAB live in an environment where the primary food source, ripe fruit, is ephemeral, often patchy, high in sugar-, and low in amino acid content. Under amino acid poor conditions in the laboratory, AAB can promote Drosophila growth and shorten development time by up to 10 days. Because we and others have shown that AAB are commonly associated with wild-caught D. melanogaster, it seems reasonable to assume that they could contribute to fly fitness and adaptation under natural conditions as well. Accordingly, associating with, and transporting growth promoting AAB to new food sources and oviposition sites should be adaptive for flies. At the same time, immotile bacteria could benefit from fly-mediated dispersal on an ephemeral and patchy resource. As a consequence, genetic variants that favor association of D. melanogaster with beneficial AAB can contribute to adaptation of both partners and should show footprints of positive selection in bacteria and flies. The proposed research will focus on the microbial symbiont side that has received less attention so far. We will study the mechanisms and molecular underpinnings of host-mediated dispersal and how they contribute to fly fitness. Therefore, we will (i) measure fly mediated bacterial dispersal and associate this trait with bacterial genes and variants in a pan-genome wide association study (pan-GWAS), (ii) find genes via transcriptional profiling that are active when primarily beneficial bacteria interact with Drosophila, and (iii) perform evolutionary analysis on the genes and variants found in the pan-GWAS and the transcriptional profiling. Finally, bacterial dispersal and fly fitness related functions of the genes from pan-GWAS and transcriptional profiling that show evidence for positive selection will be analyzed using knockout techniques and available continental scale microbial community data to understand their function in environmental adaptation. While other studies, in which Drosophila-microbe interaction is investigated, focus mostly on lab-derived bacteria or bacteria that rarely encounter flies under natural conditions, we will focus on bacteria that were isolated from wild-caught D. melanogaster, and hence could be evolutionarily relevant. Using the Drosophila-AAB model we can draw on the large population genomic and genetic resources for the host as well as a full set of genetic engineering tools for the microbes. The proposed research has the power to transform our understanding of how organisms adapt.