%0 Journal Article
%A Xing, Lei
%A Gkini, Vasiliki
%A Nieminen, Anni I.
%A Zhou, Hui-Chao
%A Aquilino, Matilde
%A Naumann, Ronald
%A Reppe, Katrin
%A Tanaka, Kohichi
%A Carmeliet, Peter
%A Heikinheimo, Oskari
%A Pääbo, Svante
%A Huttner, Wieland B.
%A Namba, Takashi
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000F-3971-2
%R 10.1038/s41467-024-47437-8
%7 2024-04-24
%D 2024
%8 24.04.2024
%* Review method: peer-reviewed
%X Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B’s ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.
%J Nature Communications
%V 15
%N 1
%] 3468
%@ 2041-1723