School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
St Vincent Clinical School, University of New South Wales, Sydney, Australia; Garvan Institute of Medical Research, EMBL Australia, Sydney, New South Wales, Australia.
Biol Psychiatry. 2022 Nov 15;92(10):760-771. doi: 10.1016/j.biopsych.2022.04.021. Epub 2022 May 19.
The higher-order cognitive functions observed in primates correlate with the evolutionary enhancement of cortical volume and folding, which in turn are driven by the primate-specific expansion of cellular diversity in the developing cortex. Underlying these changes is the diversification of molecular features including the creation of human and/or primate-specific genes, the activation of specific molecular pathways, and the interplay of diverse layers of gene regulation. We review and discuss evidence for connections between Alu elements and primate brain evolution, the evolutionary milestones of which are known to coincide along primate lineages. Alus are repetitive elements that contribute extensively to the acquisition of novel genes and the expansion of diverse gene regulatory layers, including enhancers, alternative splicing, RNA editing, and microRNA pathways. By reviewing the impact of Alus on molecular features linked to cortical expansions or gyrification or implications in cognitive deficits, we suggest that future research focusing on the role of Alu-derived molecular events in the context of brain development may greatly advance our understanding of higher-order cognitive functions and neurologic disorders.
灵长类动物表现出的高级认知功能与皮质体积和折叠的进化增强相关，而皮质体积和折叠的进化增强又受到发育中的皮质中细胞多样性的灵长类特异性扩张所驱动。这些变化的基础是分子特征的多样化，包括创造人类和/或灵长类特异性基因、激活特定的分子途径，以及不同层次的基因调控的相互作用。我们综述并讨论了 Alu 元件与灵长类脑进化之间的联系的证据，这些进化里程碑已知与灵长类谱系同时发生。Alu 是重复元件，广泛参与获得新基因和扩展多样化的基因调控层，包括增强子、选择性剪接、RNA 编辑和 microRNA 途径。通过回顾 Alu 对与皮质扩张或脑回形成相关的分子特征的影响，或对认知缺陷的影响，我们提出，未来专注于 Alu 衍生的分子事件在大脑发育背景下的作用的研究，可能会极大地促进我们对高级认知功能和神经障碍的理解。
