Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany.
Curr Opin Neurobiol. 2011 Jun;21(3):415-24. doi: 10.1016/j.conb.2011.04.008. Epub 2011 May 16.
A reduced dosage of the transcription factor FOXP2 leads to speech and language impairments probably owing to deficits in cortical and subcortical neural circuits. Based on evolutionary sequence analysis it has been proposed that the two amino acid substitutions that occurred on the human lineage have been positively selected. Here I review recent studies investigating the functional consequences of these two substitutions and discuss how these first endeavors to study human brain evolution can be interpreted in the context of speech and language evolution.
Mice carrying the two substitutions in their endogenous Foxp2 gene show specific alterations in dopamine levels, striatal synaptic plasticity and neuronal morphology. Mice carrying only one functional Foxp2, show additional and partly opposite effects suggesting that FOXP2 has contributed to tuning cortico-basal ganglia circuits during human evolution. Evidence from human and songbird studies suggest that this could have been relevant during language acquisition or vocal learning, respectively.
FOXP2 could have contributed to the evolution of human speech and language by adapting cortico-basal ganglia circuits. More generally the recent studies allow careful optimism that aspects of human brain evolution can be investigated in model systems such as the mouse.
目的：转录因子 FOXP2 的低剂量表达可能导致言语和语言障碍，这可能是由于皮质和皮质下神经回路的缺陷所致。基于进化序列分析，已经提出人类谱系中发生的两个氨基酸取代是被正选择的。在这里，我回顾了最近研究这些两个取代的功能后果，并讨论了如何在言语和语言进化的背景下解释这些首次研究人类大脑进化的努力。
发现：在其内源性 Foxp2 基因中携带这两个取代的小鼠显示多巴胺水平、纹状体突触可塑性和神经元形态的特定改变。只携带一个功能性 Foxp2 的小鼠显示出另外的、部分相反的影响，这表明 FOXP2 在人类进化过程中有助于调节皮质基底神经节回路。来自人类和鸣禽研究的证据表明，这可能与语言习得或发声学习分别有关。
总结：FOXP2 可能通过适应皮质基底神经节回路促进了人类言语和语言的进化。更一般地说，最近的研究让人们谨慎乐观地认为，可以在模型系统（如小鼠）中研究人类大脑进化的某些方面。
