A Deep Catalog of Autosomal Single Nucleotide Variation in the Pig

A comprehensive catalog of variability in a given species is useful for many important purposes, e.g., designing high density arrays or pinpointing potential mutations of economic or physiological interest. Here we provide a genomewide, worldwide catalog of single nucleotide variants by simultaneously analyzing the shotgun sequence of 128 pigs and five suid outgroups. Despite the high SNP missing rate of some individuals (up to 88%), we retrieved over 48 million high quality variants. Of them, we were able to assess the ancestral allele of more than 39M biallelic SNPs. We found SNPs in 21,455 out of the 25,322 annotated genes in pig assembly 10.2. The annotation showed that more than 40% of the variants were novel variants, not present in dbSNP. Surprisingly, we found a large variability in transition / transversion rate along the genome, which is very well explained (R2=0.79) primarily by genome differences in in CpG content and recombination rate. The number of SNPs per window also varied but was less dependent of known factors such as gene density, missing rate or recombination (R2=0.48). When we divided the samples in four groups, Asian wild boar (ASWB), Asian domestics (ASDM), European wild boar (EUWB) and European domestics (EUDM), we found a marked correlation in allele frequencies between domestics and wild boars within Asia and within Europe, but not across continents, due to the large evolutive distance between pigs of both continents (~1.2 MYA). In general, the porcine species showed a small percentage of SNPs exclusive of each population group. EUWB and EUDM were predicted to harbor a larger fraction of potentially deleterious mutations, according to the SIFT algorithm, than Asian samples, perhaps a result of background selection being less effective due to a lower effective population size in Europe.针对特定物种构建全面的变异图谱，可服务于诸多重要应用场景，例如设计高密度阵列（high density arrays），或是精准定位具有经济或生理学研究价值的潜在突变位点。本研究通过同步分析128头家猪与5个猪科外类群（suid outgroups）的鸟枪测序（shotgun sequence）数据，构建了全基因组范围、覆盖全球的单核苷酸变异（single nucleotide variants, SNVs）图谱。尽管部分个体的单核苷酸多态性（single nucleotide polymorphism, SNPs）缺失率较高（最高达88%），但我们仍筛选得到超过4800万个高质量变异位点。其中，我们可对超过3900万个双等位基因SNP的祖先等位基因（ancestral allele）进行评估。在猪参考基因组组装版本10.2（pig assembly 10.2）注释的25322个基因中，我们在21455个基因中检测到了SNP位点。注释结果显示，超过40%的变异位点为未在dbSNP数据库中收录的新发变异。令人意外的是，我们发现基因组上的转换（transition）/颠换（transversion）比率存在显著差异，该差异主要可由基因组的CpG二核苷酸含量与重组率差异解释，拟合优度（R²）达0.79。每个基因组窗口内的SNP数量同样存在波动，但该波动与基因密度、缺失率或重组率等已知因素的相关性较弱，拟合优度仅为0.48。我们将样本划分为四组：亚洲野猪（Asian wild boar, ASWB）、亚洲家猪（Asian domestics, ASDM）、欧洲野猪（European wild boar, EUWB）与欧洲家猪（European domestics, EUDM）。研究发现，亚洲与欧洲区域内的家猪和野猪之间的等位基因频率均呈现显著相关性，但跨大陆区域则无此关联——这是由于两大洲的猪类演化距离较远（约120万年，million years ago, MYA）。总体而言，猪属物种的各群体特异性SNP占比均较低。根据SIFT算法（SIFT algorithm）预测，欧洲野猪与欧洲家猪所携带的潜在有害突变比例高于亚洲样本，这可能是由于欧洲猪群的有效种群规模更低，导致背景选择（background selection）的作用效果减弱所致。