Zug Roman, Uller Tobias
Department of Biology, Lund University, Lund, Sweden.
Evol Hum Sci. 2022 Sep 26;4:e43. doi: 10.1017/ehs.2022.42. eCollection 2022.
Evolutionary changes in brain and craniofacial development have endowed humans with unique cognitive and social skills, but also predisposed us to debilitating disorders in which these traits are disrupted. What are the developmental genetic underpinnings that connect the adaptive evolution of our cognition and sociality with the persistence of mental disorders with severe negative fitness effects? We argue that loss of function of genes involved in transcriptional regulation represents a crucial link between the evolution and dysfunction of human cognitive and social traits. The argument is based on the haploinsufficiency of many transcriptional regulator genes, which makes them particularly sensitive to loss-of-function mutations. We discuss how human brain and craniofacial traits evolved through partial loss of function (i.e. reduced expression) of these genes, a perspective compatible with the idea of human self-domestication. Moreover, we explain why selection against loss-of-function variants supports the view that mutation-selection-drift, rather than balancing selection, underlies the persistence of psychiatric disorders. Finally, we discuss testable predictions.
大脑和颅面发育的进化变化赋予了人类独特的认知和社交技能，但也使我们易患那些这些特质遭到破坏的衰弱性疾病。将我们认知和社会性的适应性进化与具有严重负面健康影响的精神障碍的持续存在联系起来的发育遗传学基础是什么？我们认为，参与转录调控的基因功能丧失是人类认知和社会特质的进化与功能障碍之间的关键联系。这一观点基于许多转录调节基因的单倍剂量不足，这使得它们对功能丧失突变特别敏感。我们讨论了人类大脑和颅面特征如何通过这些基因的部分功能丧失（即表达降低）而进化，这一观点与人类自我驯化的概念相符。此外，我们解释了为什么针对功能丧失变异的选择支持这样一种观点，即突变-选择-漂变而非平衡选择是精神障碍持续存在的基础。最后，我们讨论了可检验的预测。
