ArhGAP11B and human encephalisation
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A gene appearing after the divergence from chimpanzee controls neural progenitors proliferation and can cause neocortex folding .
ARHGAP11B is a human-specific gene that amplifies basal progenitors and is capable of causing neocortex folding in mouse. This likely reflects a role for ARHGAP11B in development and evolutionary expansion of the human neocortex, a conclusion consistent with the finding that the gene duplication that created ARHGAP11B occurred on the human lineage after the divergence from the chimpanzee lineage but before the divergence from Neandertals, whose brain size was similar to that of modern humans.[1] (*)
Structure ARHGAP11B contains 267 amino-acids and is a truncated version of ARHGAP11A. ARHGAP11B arose on the human evolutionary lineage after the divergence from the chimpanzee lineage by partial duplication of ARHGAP11A, which is found throughout the animal kingdom and encodes a Rho GTPase-activating-protein (RhoGAP domain). ARHGAP11B exists not only in present-day humans but also in Neandertals and Denisovans. ARHGAP11B comprises most of the GAP-domain (until lysine-220) followed by a novel C-terminal sequence but lacking the C-terminal 756 amino acids of ARHGAP11A.
Activity In contrast to full-length ARHGAP11A and ARHGAP11A 1-250, ARHGAP11B, like ARHGAP11A1-220, did not exhibit RhoGAP activity in a RhoA/Rho-kinase–based cell transfection assay . This indicates that the C-terminal 47 amino-acids of ARHGAP11B (after lysine-220) constitute not only a unique sequence, resulting from a frameshifting deletion, but also are functionally distinct from their counterpart in ARHGAP11A. In this assay, co-expression of ARHGAP11B along with ARHGAP11A did not inhibit the latter's RhoGAP activity.[2]
Function Since several genes involved in mental retardation encode proteins with RhoGAP domains or other proteins in the Rho signalling pathway it does not come as a complete surprise that ARHGAP11B is involved in neocortex folding, however its precise function is still unknown. ARHGAP11B could bind to specific Rho family members, or other partners in this pathway.
References
- ↑ Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion Marta Florio, Mareike Albert, Elena Taverna, Takashi Namba, Holger Brandl, Eric Lewitus, Christiane Haffner, Alex Sykes, Fong Kuan Wong, Jula Peters, Elaine Guhr, Sylvia Klemroth, Kay Prüfer, Janet Kelso, Ronald Naumann, Ina Nüsslein, Andreas Dahl, Robert Lachmann, Svante Pääbo, and Wieland B. Huttner Science aaa1975Published online 26 February 2015 [DOI:10.1126/science.aaa1975]
- ↑ Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion Marta Florio, Mareike Albert, Elena Taverna, Takashi Namba, Holger Brandl, Eric Lewitus, Christiane Haffner, Alex Sykes, Fong Kuan Wong, Jula Peters, Elaine Guhr, Sylvia Klemroth, Kay Prüfer, Janet Kelso, Ronald Naumann, Ina Nüsslein, Andreas Dahl, Robert Lachmann, Svante Pääbo, and Wieland B. Huttner Science aaa1975Published online 26 February 2015 [DOI:10.1126/science.aaa1975]
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