Dweep Harsh, Kubikova Nada, Gretz Norbert, Voskarides Konstantinos, Felekkis Kyriacos
Medical Research Center, University of Heidelberg, Mannheim, Germany.
Department of Life and Health Sciences, University of Nicosia, Nicosia Cyprus.
Sci Rep. 2015 Jul 16;5:12163. doi: 10.1038/srep12163.
Gene expression regulation is a complex and highly organized process involving a variety of genomic factors. It is widely accepted that differences in gene expression can contribute to the phenotypic variability between species, and that their interpretation can aid in the understanding of the physiologic variability. CNVs and miRNAs are two major players in the regulation of expression plasticity and may be responsible for the unique phenotypic characteristics observed in different lineages. We have previously demonstrated that a close interaction between these two genomic elements may have contributed to the regulation of gene expression during evolution. This work presents the molecular interactions between CNV and non CNV genes with miRNAs and other genomic elements in eight different species. A comprehensive analysis of these interactions indicates a unique nature of human CNV genes regulation as compared to other species. By using genes with short 3' UTR that abolish the "canonical" miRNA-dependent regulation, as a model, we demonstrate a distinct and tight regulation of human genes that might explain some of the unique features of human physiology. In addition, comparison of gene expression regulation between species indicated that there is a significant difference between humans and mice possibly questioning the effectiveness of the latest as experimental models of human diseases.
基因表达调控是一个复杂且高度有序的过程，涉及多种基因组因素。人们普遍认为，基因表达的差异会导致物种间的表型变异性，并且对其进行解读有助于理解生理变异性。拷贝数变异（CNV）和微小RNA（miRNA）是表达可塑性调控中的两个主要因素，可能是不同谱系中观察到的独特表型特征的原因。我们之前已经证明，这两个基因组元件之间的密切相互作用可能在进化过程中对基因表达调控起到了作用。这项工作展示了八个不同物种中CNV基因和非CNV基因与miRNA及其他基因组元件之间的分子相互作用。对这些相互作用的全面分析表明，与其他物种相比，人类CNV基因调控具有独特性。通过使用具有短3'非翻译区（UTR）从而消除“经典”miRNA依赖性调控的基因作为模型，我们证明了人类基因存在独特且紧密的调控，这可能解释了人类生理学的一些独特特征。此外，物种间基因表达调控的比较表明，人类和小鼠之间存在显著差异，这可能会质疑将小鼠作为人类疾病实验模型的有效性。
