Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Adaptation to a Changing Environment, Institute of Integrative Biology, ETH Zürich, CH-8092, Zürich, Switzerland.
BMC Genomics. 2018 Jun 27;19(1):496. doi: 10.1186/s12864-018-4806-7.
Genome scans based on outlier analyses have revolutionized detection of genes involved in adaptive processes, but reports of some forms of selection, such as balancing selection, are still limited. It is unclear whether high throughput genotyping approaches for identification of single nucleotide polymorphisms have sufficient power to detect modes of selection expected to result in reduced genetic differentiation among populations. In this study, we used Arabidopsis lyrata to investigate whether signatures of balancing selection can be detected based on genomic smoothing of Restriction Associated DNA sequencing (RAD-seq) data. We compared how different sampling approaches (both within and between subspecies) and different background levels of polymorphism (inbreeding or outcrossing populations) affected the ability to detect genomic regions showing key signatures of balancing selection, specifically elevated polymorphism, reduced differentiation and shifts towards intermediate allele frequencies. We then tested whether candidate genes associated with disease resistance (R-gene analogs) were detected more frequently in these regions compared to other regions of the genome.
We found that genomic regions showing elevated polymorphism contained a significantly higher density of R-gene analogs predicted to be under pathogen-mediated selection than regions of non-elevated polymorphism, and that many of these also showed evidence for an intermediate site-frequency spectrum based on Tajima's D. However, we found few genomic regions that showed both elevated polymorphism and reduced F among populations, despite strong background levels of genetic differentiation among populations. This suggests either insufficient power to detect the reduced population structure predicted for genes under balancing selection using sparsely distributed RAD markers, or that other forms of diversifying selection are more common for the R-gene analogs tested.
Genome scans based on a small number of individuals sampled from a wide range of populations were sufficient to confirm the relative scarcity of signatures of balancing selection across the genome, but also identified new potential disease resistance candidates within genomic regions showing signatures of balancing selection that would be strong candidates for further sequencing efforts.
基于异常值分析的基因组扫描极大地推动了参与适应性过程的基因的检测，但某些形式的选择（如平衡选择）的报道仍然有限。目前尚不清楚高通量基因分型方法是否有足够的能力来检测预期会导致种群间遗传分化减少的选择模式。在这项研究中，我们使用拟南芥 lyrata 来研究基于限制性相关 DNA 测序（RAD-seq）数据的基因组平滑是否可以检测到平衡选择的特征。我们比较了不同的采样方法（亚种内和亚种间）和不同的多态性背景水平（自交或异交群体）如何影响检测显示平衡选择关键特征的基因组区域的能力，特别是升高的多态性、降低的分化和向中间等位基因频率的转变。然后，我们测试了与疾病抗性（R 基因类似物）相关的候选基因是否比基因组其他区域更频繁地在这些区域中被检测到。
我们发现，显示升高多态性的基因组区域包含的预测受病原体介导选择的 R 基因类似物的密度显著高于非升高多态性区域，并且许多区域还基于 Tajima 的 D 显示出中间位点频率谱的证据。然而，尽管种群间存在很强的遗传分化背景，但我们发现很少有基因组区域同时显示升高的多态性和降低的 F 间种群间分化。这表明，使用稀疏分布的 RAD 标记检测平衡选择下基因预测的降低的种群结构的能力不足，或者测试的 R 基因类似物受到其他形式的多样化选择更为常见。
基于从广泛的种群中采样的少数个体进行的基因组扫描足以确认整个基因组中平衡选择特征的相对稀缺性，但也在显示平衡选择特征的基因组区域内鉴定了新的潜在疾病抗性候选基因，这些候选基因将是进一步测序工作的强有力候选基因。
