RADseq underestimates diversity and introduces genealogical biases due to nonrandom haplotype sampling
RADseq underestimates diversity and introduces genealogical biases due to nonrandom haplotype sampling
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DOI：
10.1111/mec.12276
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发表时间：
2013-06-01
影响因子：
4.9
通讯作者：
Bomblies, K.
中科院分区：
文献类型：
--
作者：
Arnold, B.;Corbett-Detig, R. B.;Bomblies, K.
基于限制性消化的简化代表性基因组测序方法能够实现大规模标记生成，并促进各种模型和非模型系统中的基因组研究。然而，由于限制性位点的多态性，基于限制性消化的染色体采样可能会在等位基因频率估计中引入偏差。为了探索这种非随机采样的影响及其对不同进化参数的敏感性，我们开发了一个合并模拟框架来模拟基于限制性短读长测序实验（RADseq）中染色体的偏向恢复。我们分析了模拟的 DNA 序列数据集，并将模拟的已知值与使用 RADseq 方法从相同样本估计的值进行比较。我们比较常用汇总统计量、Tajima 的 D 和 FST 的真实值和估计值。我们表明，缺失单倍型的基因座估计的汇总统计值可能与真实值有很大偏差，并且对于特定的谱系历史也有所丰富。这些偏差对非平衡人口统计很敏感，例如瓶颈和人口扩张。对 102 个完全测序的果蝇基因组进行计算机消化，得到的结果与我们的聚结模拟结果相似。尽管 RADseq 在非模型系统中进行标记发现和性状绘图的潜力仍然无可争议，但我们的结果敦促在应用该技术进行群体遗传推断时要谨慎。
Reduced representation genome-sequencing approaches based on restriction digestion are enabling large-scale marker generation and facilitating genomic studies in a wide range of model and nonmodel systems. However, sampling chromosomes based on restriction digestion may introduce a bias in allele frequency estimation due to polymorphisms in restriction sites. To explore the effects of this nonrandom sampling and its sensitivity to different evolutionary parameters, we developed a coalescent-simulation framework to mimic the biased recovery of chromosomes in restriction-based short-read sequencing experiments (RADseq). We analysed simulated DNA sequence datasets and compared known values from simulations with those that would be estimated using a RADseq approach from the same samples. We compare these true' and estimated' values of commonly used summary statistics, , w, Tajima's D and FST. We show that loci with missing haplotypes have estimated summary statistic values that can deviate dramatically from true values and are also enriched for particular genealogical histories. These biases are sensitive to nonequilibrium demography, such as bottlenecks and population expansion. In silico digests with 102 completely sequenced Drosophila melanogaster genomes yielded results similar to our findings from coalescent simulations. Though the potential of RADseq for marker discovery and trait mapping in nonmodel systems remains undisputed, our results urge caution when applying this technique to make population genetic inferences.