Dwyer Donard S
Departments of Psychiatry and Behavioral Medicine and Pharmacology, Toxicology and Neuroscience, LSU Health Shreveport, Shreveport, Louisiana, USA.
Complex Psychiatry. 2020 Oct;6(1-2):20-29. doi: 10.1159/000507988. Epub 2020 Apr 21.
The processes that created the primordial genome are inextricably linked to current day vulnerability to developing a psychiatric disorder as summarized in this review article. Chaos and dynamic forces including duplication, transposition, and recombination generated the protogenome. To survive early stages of genome evolution, self-organization emerged to curb chaos. Eventually, the human genome evolved through a delicate balance of chaos/instability and organization/stability. However, recombination coldspots, silencing of transposable elements, and other measures to limit chaos also led to retention of variants that increase risk for disease. Moreover, ongoing dynamics in the genome creates various new mutations that determine liability for psychiatric disorders. Homologous recombination, long-range gene regulation, and gene interactions were all guided by spooky action-at-a-distance, which increased variability in the system. A probabilistic system of life was required to deal with a changing environment. This ensured the generation of outliers in the population, which enhanced the probability that some members would survive unfavorable environmental impacts. Some of the outliers produced through this process in man are ill suited to cope with the complex demands of modern life. Genomic chaos and mental distress from the psychological challenges of modern living will inevitably converge to produce psychiatric disorders in man.
如本综述文章所总结,创造原始基因组的过程与当前患精神疾病的易感性有着千丝万缕的联系。包括复制、转座和重组在内的混乱和动态力量产生了原基因组。为了在基因组进化的早期阶段生存下来,自我组织应运而生以抑制混乱。最终,人类基因组通过混乱/不稳定与组织/稳定之间的微妙平衡而进化。然而,重组冷点、转座元件的沉默以及其他限制混乱的措施也导致了增加疾病风险的变异的保留。此外,基因组中持续的动态变化产生了各种新的突变,这些突变决定了患精神疾病的倾向。同源重组、长程基因调控和基因相互作用都受到超距作用的引导,这增加了系统的变异性。需要一个概率性的生命系统来应对不断变化的环境。这确保了种群中异常值的产生,从而提高了一些成员在不利环境影响下存活的概率。人类通过这个过程产生的一些异常值并不适合应对现代生活的复杂需求。基因组混乱和现代生活心理挑战带来的精神困扰将不可避免地相互交织,导致人类患上精神疾病。