MCPH1 is a gene encoding a multi-functional protein involved in DNA repair, regulation of cell cycling and apoptosis, and regulation of neurogenesis. This gene has shown to be rapidly evolving and has accumulated seven human-specific amino acid changes and shown differences in levels of expression between humans and rhesus monkeys. 11 transgenic rhesus monkeys with human copies of MCPH1 were produced. These monkeys exhibited more human-like neotenic brain development in the form of slower growth of grey matter volume (164 day delay to reach peak compared to WT). Analysis of a marker gene for brain cell maturation, NeuN, showed transgenic monkeys with significantly lower counts of NeuN presenting cells compared to control. Transcriptomic analyses further showed that transgenic monkeys had higher expression of MCPH1 and downregulation of genes involved in neuronal differentiation and development. Interestingly, the brains of the transgenic monkeys were not found to be enlarged, despite the developmental delays. Thus, this study demonstrates the potential usefulness of using primate models to answer questions of human evolutionary development and also brings up questions about ethical animal experimentation.
Audrey Tjahjadi
Link to original article: https://academic.oup.com/nsr/article/6/3/480/5420749
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