Molecular architecture of environmental adaptation in natural populations of the nematode Caenorhabditis elegans

几乎所有物种都在面对持续的环境挑战时调整其生活史或行为。在这些条件下，两种不同的适应性反应是有利的：表型塑性反应和进化反应。在表型可塑性反应的情况下，选择有利于个体通过调整代谢过程或特定行为来适应的能力。因此，适应是在转录组或蛋白质组水平上确定的。在进化反应的情况下，选择作用于种群的遗传组成，这是不同死亡率和繁殖成功率的结果。因此，适应性表现在DNA水平上。在这两种反应中，适应度最大化的选择受到权衡的限制，例如以牺牲后代数量为代价来增加抗逆性。但到目前为止，1）哪些基因是自然选择的目标，它们如何促成表型变异，以及2）在不同环境制度下，自然种群中如何调节权衡。我们将通过研究C.优雅它是一种世界性线虫，显示出高度的本地遗传多样性，可进行分子高通量筛选，并允许基因型和表型之间的关联，以查明负责表型变异的基因座。我们将i）在2个不同的地点和2个不同的栖息地分离240个野生型菌株及其相关的微生物，ii）测量所有菌株中的SNP变异和转录组，iii）测量表型变异和响应于生物和非生物应激的权衡，iv）使用关联作图搜索候选基因，和v）使用RNAi敲低验证这些候选物。我们是最早将联合收割机表型筛选、关联作图和RNAi介导的基因验证相结合并揭示自然种群适应的分子结构的倡议之一。

Almost all species adapt their life-history or behaviour in the face of continuous environmental challenges. Two distinct adaptive responses can be favoured under these conditions: a phenotypic plastic response and an evolutionary response. In case of a phenotypic plastic response, selection favoured the ability of individuals to adapt by adjusting metabolic processes or specific behaviours. Adaptation is thus determined at the transcriptomic or proteomic level. In case of an evolutionary response, selection acts on the genetic composition of the population as a consequence of differential mortality and reproductive success. Adaptation is thus manifested at the DNA level. In both responses, the options for fitness maximization are constrained by trade-offs such as increasing stress resistance at the cost of offspring number.But so far it is unknown 1) which genes are the target of natural selection and how they contribute to phenotypic variation, and 2) how trade-offs are regulated in natural populations under different environmental regimes. We will address these questions by studying natural populations of C. elegans. It is a cosmopolitan nematode displaying high local genetic diversity, accessible to molecular high-throughput screens and allows for associations between genotype and phenotype to pinpoint the loci responsible for phenotypic variation. We will i) isolate 240 wildtype strains and their associated micro-organisms at 2 different locations and 2 distinct habitats, ii) measure SNP variation and the transcriptome in all strains, iii) measure phenotypic variation and trade-offs in response to the biotic and abiotic stressors, iv) search for candidate genes using association mapping, and v) validate these candidates using RNAi knock-downs.By taking advantage of the model C. elegans we are one of the first initiatives to combine phenotypic screens, association mapping and RNAi-mediated gene validation and unravel the molecular architecture of adaptation in natural populations.