Babbitt Courtney C, Haygood Ralph, Nielsen William J, Wray Gregory A
Department of Biology, Duke University, Durham, NC, 27708, USA.
Institute for Genome Sciences & Policy, Duke University, Durham, NC, 27708, USA.
BMC Genomics. 2017 Jun 5;18(1):435. doi: 10.1186/s12864-017-3831-2.
Despite evidence for adaptive changes in both gene expression and non-protein-coding, putatively regulatory regions of the genome during human evolution, the relationship between gene expression and adaptive changes in cis-regulatory regions remains unclear.
Here we present new measurements of gene expression in five tissues of humans and chimpanzees, and use them to assess this relationship. We then compare our results with previous studies of adaptive noncoding changes, analyzing correlations at the level of gene ontology groups, in order to gain statistical power to detect correlations.
Consistent with previous studies, we find little correlation between gene expression and adaptive noncoding changes at the level of individual genes; however, we do find significant correlations at the level of biological function ontology groups. The types of function include processes regulated by specific transcription factors, responses to genetic or chemical perturbations, and differentiation of cell types within the immune system. Among functional categories co-enriched with both differential expression and noncoding adaptation, prominent themes include cancer, particularly epithelial cancers, and neural development and function.
尽管有证据表明在人类进化过程中基因组的基因表达和非蛋白质编码的假定调控区域都发生了适应性变化，但基因表达与顺式调控区域适应性变化之间的关系仍不清楚。
在此，我们展示了人类和黑猩猩五种组织中基因表达的新测量结果，并利用它们来评估这种关系。然后，我们将结果与之前关于适应性非编码变化的研究进行比较，分析基因本体组水平上的相关性，以便获得检测相关性的统计能力。
与之前的研究一致，我们发现在单个基因水平上基因表达与适应性非编码变化之间几乎没有相关性；然而，我们确实在生物学功能本体组水平上发现了显著的相关性。功能类型包括由特定转录因子调控的过程、对遗传或化学扰动的反应以及免疫系统内细胞类型的分化。在差异表达和非编码适应性共同富集的功能类别中，突出的主题包括癌症，特别是上皮癌，以及神经发育和功能。
