Regional Regulation of Transcription in the Bovine Genome

Eukaryotic genes are distributed along chromosomes as clusters of highly expressed genes termed RIDGEs (Regions of IncreaseD Gene Expression) and lowly expressed genes termed anti-RIDGEs, interspersed among genes expressed at intermediate levels or not expressed. Previous studies based on this observation suggested a dual mechanism of gene regulation, where, in addition to transcription factors, the chromosomal domain influences the expression level of their embedded genes. The objectives here were to provide evidence for the existence of chromosomal regional regulation of transcription in the bovine genome, to analyse the genomic features of genes located within RIDGEs versus anti-RIDGEs and tissue-specific genes versus housekeeping and to examine the genomic distribution of genes subject to positive selection in bovines. Gene expression analysis of four brain tissues and the anterior pituitary of 28 cows identified 70 RIDGEs and 41 anti-RIDGEs (harbouring 3735 and 1793 bovine genes respectively) across the bovine genome which are significantly higher than expected by chance. Housekeeping genes (defined here as genes expressed in all five tissues) were over-represented within RIDGEs but tissue-specific genes (genes expressed in only one of the five tissues) were not. Housekeeping genes and genes within RIDGEs had, in general, higher expression levels and GC content but shorter gene lengths and intron lengths than tissue-specific genes and genes within anti-RIDGES. Our findings suggest the existence of chromosomal regional regulation of transcription in the bovine genome. The genomic features observed for genes within RIDGEs and housekeeping genes in bovines agree with previous studies in several other species further strengthening the hypothesis of selective pressure to keep the highly and widely expressed genes short and compact for transcriptional efficiency. Further, positively selected genes were found non-randomly distributed on the genome with a preference for RIDGEs and regions of intermediate gene expression compared to anti-RIDGEs.

真核生物基因沿染色体呈簇状分布：高表达基因簇被命名为RIDGEs（Regions of IncreaseD Gene Expression，即基因表达升高区域），低表达基因簇则被命名为anti-RIDGEs，二者散布于表达水平中等或不表达的基因之间。基于这一发现的既往研究提出了基因调控的双重机制：除转录因子外，染色体结构域也会影响其内嵌基因的表达水平。本研究旨在：为牛基因组中存在染色体区域化转录调控提供证据，分析RIDGEs与anti-RIDGEs内基因、组织特异性基因（tissue-specific genes）与管家基因（housekeeping genes）的基因组特征，并探究牛基因组中受正向选择（positive selection）的基因的基因组分布情况。对28头奶牛的4种脑组织及脑垂体前叶进行基因表达分析后，在牛全基因组中鉴定出70个RIDGEs与41个anti-RIDGEs，分别包含3735和1793个牛基因，其数量显著高于随机预期水平。管家基因（本研究定义为在全部5种组织中均表达的基因）在RIDGEs中显著富集，而组织特异性基因（仅在5种组织中的1种内表达的基因）则无此富集现象。总体而言，管家基因与RIDGEs内的基因，相较于组织特异性基因及anti-RIDGEs内的基因，具有更高的表达水平与GC含量，但基因长度及内含子长度更短。本研究结果证实牛基因组中存在染色体区域化转录调控现象。牛RIDGEs内基因与管家基因所呈现的基因组特征，与其他多个物种的既往研究结果一致，进一步支持了这一假说：为提升转录效率，自然选择压力倾向于保留高表达且广泛表达的短而紧凑的基因。此外，研究发现受正向选择的基因在基因组中的分布并非随机，相较于anti-RIDGEs，它们更偏好富集于RIDGEs及中等基因表达水平区域。