Wang Mi, Uebbing Severin, Ellegren Hans
Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Sweden.
Genome Biol Evol. 2017 May 1;9(5):1266-1279. doi: 10.1093/gbe/evx080.
Polymorphism in cis-regulatory sequences can lead to different levels of expression for the two alleles of a gene, providing a starting point for the evolution of gene expression. Little is known about the genome-wide abundance of genetic variation in gene regulation in natural populations but analysis of allele-specific expression (ASE) provides a means for investigating such variation. We performed RNA-seq of multiple tissues from population samples of two closely related flycatcher species and developed a Bayesian algorithm that maximizes data usage by borrowing information from the whole data set and combines several SNPs per transcript to detect ASE. Of 2,576 transcripts analyzed in collared flycatcher, ASE was detected in 185 (7.2%) and a similar frequency was seen in the pied flycatcher. Transcripts with statistically significant ASE commonly showed the major allele in >90% of the reads, reflecting that power was highest when expression was heavily biased toward one of the alleles. This would suggest that the observed frequencies of ASE likely are underestimates. The proportion of ASE transcripts varied among tissues, being lowest in testis and highest in muscle. Individuals often showed ASE of particular transcripts in more than one tissue (73.4%), consistent with a genetic basis for regulation of gene expression. The results suggest that genetic variation in regulatory sequences commonly affects gene expression in natural populations and that it provides a seedbed for phenotypic evolution via divergence in gene expression.
顺式调控序列中的多态性可导致基因的两个等位基因具有不同水平的表达，为基因表达的进化提供了一个起点。对于自然种群中基因调控方面遗传变异的全基因组丰度，我们了解甚少，但等位基因特异性表达（ASE）分析为研究此类变异提供了一种手段。我们对两种亲缘关系密切的鹟科鸟类种群样本的多个组织进行了RNA测序，并开发了一种贝叶斯算法，该算法通过从整个数据集中借用信息来最大化数据使用，并结合每个转录本的多个单核苷酸多态性（SNP）来检测ASE。在白领姬鹟中分析的2576个转录本中，有185个（7.2%）检测到了ASE，在斑姬鹟中也观察到了类似的频率。具有统计学显著ASE的转录本通常在超过90%的读数中显示主要等位基因，这反映出当表达严重偏向于其中一个等位基因时，检测能力最高。这表明观察到的ASE频率可能被低估了。ASE转录本的比例在不同组织中有所不同，在睾丸中最低，在肌肉中最高。个体通常在不止一个组织中表现出特定转录本的ASE（73.4%），这与基因表达调控的遗传基础一致。结果表明，调控序列中的遗传变异通常会影响自然种群中的基因表达，并且它通过基因表达的差异为表型进化提供了一个温床。
