Changes in gene expression play an important role in evolution and can be relevant to evolutionary medicine. In this work, a strong relationship was found between the statistical significance of evolutionary changes in the expression of orthologous genes in the five or six homologous mammalian tissues and the across-tissues unidirectionality of changes (i.e., they occur in the same direction in different tissues -- all upward or all downward). In the area of highly significant changes, the fraction of unidirectionally changed genes (UCG) was above 0.9 (random expectation is 0.03). This observation indicates that the most pronounced evolutionary changes in mammalian gene expression are systemic (i.e., they operate at the whole-organism level). The UCG are strongly enriched in the housekeeping genes. More specifically, in the human-chimpanzee comparison, the UCG are enriched in the pathways belonging to gene expression (translation is prominent), cell cycle control, ubiquitin-dependent protein degradation (mostly related to cell cycle control), apoptosis, and Parkinson's disease. In the human-macaque comparison, the two other neurodegenerative diseases (Alzheimer's and Huntington's) are added to the enriched pathways. The consolidation of gene expression changes at the level of pathways indicates that they are not neutral but functional. The systemic expression changes probably maintain the across-tissues balance of basic physiological processes in the course of evolution (e.g., during the movement along the fast-slow life axis). These results can be useful for understanding the variation in longevity and susceptibility to cancer and widespread neurodegenerative diseases. This approach can also guide the choice of prospective genes for studies aiming to decipher cis-regulatory code (the gene list is provided).

基因表达的变化在进化中起着重要作用，并且可能与进化医学有关。在这项工作中，发现了五个或六个同源哺乳动物组织中直系同源基因表达的进化变化的统计显着性与跨组织单向性变化（即它们在不同组织中以相同方向发生）之间的强烈关系。 -- 全部向上或全部向下）。在高度显着变化的区域，单向变化基因（UCG）的比例在0.9以上（随机期望为0.03）。这一观察表明哺乳动物基因表达最显着的进化变化是系统性的（即，它们在整个生物体水平上运作）。UCG 富含看家基因。进一步来说，在人与黑猩猩的比较中，UCG 在属于基因表达（翻译突出）、细胞周期控制、泛素依赖性蛋白质降解（主要与细胞周期控制相关）、细胞凋亡和帕金森病的通路中富集。在人类与猕猴的比较中，另外两种神经退行性疾病（阿尔茨海默病和亨廷顿病）被添加到丰富的途径中。通路水平上基因表达变化的整合表明它们不是中性的而是功能性的。在进化过程中（例如，在沿着快-慢生命轴的运动过程中），全身性表达的变化可能维持了基本生理过程的跨组织平衡。这些结果可用于了解寿命的变化以及对癌症和广泛的神经退行性疾病的易感性。这种方法还可以指导旨在破译顺式调控代码的研究的前瞻性基因的选择（提供了基因列表）。