Center of Brain Neurobiology and Neurogenetics, Institute of Cytology and Genetics SB RAS, Lavrentyeva Ave. 10, 630090, Novosibirsk, Russia.
Systems Biology Department, Institute of Cytology and Genetics SB RAS, Lavrentyeva Ave. 10, 630090, Novosibirsk, Russia.
Mol Neurobiol. 2018 Mar;55(3):1871-1904. doi: 10.1007/s12035-017-0427-4. Epub 2017 Feb 24.
Adaptability to a variety of environmental conditions is a prominent feature of Homo sapiens. We hypothesize that this feature can be explained by evolutionary changes in gene promoters active in the brain prefrontal cortex leading to a more flexible gene regulation network. The genotype-dependent range of gene expression can be broader in humans than in other higher primates. Thus, we searched for specific signatures of evolutionary changes in promoter architectures of multiple hominid genes, including the genes active in human cortical neurons that may indicate an increase of variability of gene expression rather than just changes in the level of expression, such as downregulation or upregulation of the genes. We performed a whole-genome search for genetic-based alterations that may impact gene regulation "flexibility" in a process of hominids evolution, such as (i) CpG dinucleotide content, (ii) predicted nucleosome-DNA dissociation constant, and (iii) predicted affinities for TATA-binding protein (TBP) in gene promoters. We tested all putative promoter regions across the human genome and especially gene promoters in active chromatin state in neurons of prefrontal cortex, the brain region critical for abstract thinking and social and behavioral adaptation. Our data imply that the origin of modern man has been associated with an increase of flexibility of promoter-driven gene regulation in brain. In contrast, after splitting from the ancestral lineages of H. sapiens, the evolution of ape species is characterized by reduced flexibility of gene promoter functioning, underlying reduced variability of the gene expression.
适应各种环境条件是智人的一个显著特征。我们假设，这种特征可以通过大脑前额叶皮层中活跃的基因启动子的进化变化来解释，这些变化导致了更灵活的基因调控网络。人类的基因型依赖性基因表达范围可能比其他高等灵长类动物更广泛。因此，我们搜索了多种人类基因启动子结构中进化变化的特定特征，包括在人类皮质神经元中活跃的基因，这些基因可能表明基因表达的可变性增加，而不仅仅是表达水平的变化，例如基因的下调或上调。我们进行了全基因组搜索，以寻找可能影响人类进化过程中基因调控“灵活性”的遗传改变，例如：(i) CpG 二核苷酸含量，(ii) 预测核小体-DNA 解离常数，以及 (iii) 基因启动子中 TATA 结合蛋白 (TBP) 的预测亲和力。我们测试了人类基因组中所有可能的启动子区域，特别是前额叶皮层神经元中活跃染色质状态下的基因启动子，前额叶皮层是抽象思维和社会行为适应的关键脑区。我们的数据表明，现代人的起源与大脑中启动子驱动的基因调控灵活性的增加有关。相比之下，在与人类祖先谱系分离后，猿类物种的进化特征是基因启动子功能的灵活性降低，导致基因表达的可变性降低。
