Adaptive evolution of immune gene families: origin, diversification and diversity of the NLR genes in zebrafish

宿主与其病原体之间的共同进化军备竞赛是宿主免疫库快速进化动力学的主要驱动力。在这个过程中的一个关键方面是宿主免疫系统的组成部分的高度多样性。 在这个项目中，我们将重点关注这种快速多样化背后的机制，并研究斑马鱼自然种群中所谓的NLR基因家族的进化。这个基因家族以及实验生物非常适合分析宿主的生态适应性。斑马鱼是遗传学和免疫学研究中公认的模式生物。最近发布的一个新的高质量的基因组组装提供了一个强大的基础，进化基因组学。 本项目中的目标基因构成了一个非常大的，最近扩展的，大约有400个成员的斑马鱼家族。为了了解形成这个基因家族和编码蛋白质的进化和适应力的性质，我们将从不同生态条件的不同野生种群中收集大规模的基因组序列数据（例如，原始与污染的沃茨），并利用公开的以及定制和自主开发的种群遗传学方法分析这些数据。该项目将剖析最近适应事件的动态，以及在暴露于不同环境的种群中形成该基因家族多样化的机制。特别是，我们将针对斑马鱼4号染色体上的密集NLR簇。对于这些基因及其上游调控区域，我们将确定突变频率谱，测量基因和编码蛋白的进化速率和选择性约束。我们希望确定一组进化热点，这些热点已经受到环境触发的适应。这些将是未来在后续转录组学（宿主）和元基因组学（环境）实验中进行功能研究的主要候选者。

The co-evolutionary arms race between hosts and their pathogens is the major driver of the rapid evolutionary dynamics of the host immune repertoire. A key aspect in this process is the high diversity of the components of the host's immune system. In this project we will focus on the mechanisms behind this fast diversification, and study the evolution of the so-called NLR gene family in natural populations of zebrafish, Danio rerio.This gene family, as well as the experimental organism, are well suited for the analysis of the host's race for ecological adaptation. Danio rerio is an established model organism in genetic and immunological research. The recent release of a new high-quality genome assembly provides a robust basis for evolutionary genomics. The genes targeted in this project constitute an extremely large, very recently expanded, family of about 400 members in zebrafish.To understand the nature of the evolutionary and adaptive forces which have shaped this gene family and the encoded proteins we will collect large scale genomic sequence data from different wild populations with different ecological conditions (e.g., pristine vs. polluted waters) and analyse these data with publicly available as well as with customized and own-developed population genetic methods.The project will dissect the dynamics of recent adaptation events, and the mechanisms that have shaped the diversification of this gene family in populations exposed to different environments.In particular, we will target the dense NLR-cluster on chromosome 4 of Danio rerio. For these genes and their upstream regulatory regions we will determine mutation frequency spectra, measure evolutionary rates and selective constraints across genes and encoded proteins.We expect to identify a set of evolutionary hotspots, which have been subject to environmentally triggered adaptation. These will be prime candidates for future functional studies in follow-up transcriptomics (of the host) and meta-genomics (of the environment) experiments.