PT  - JOURNAL ARTICLE
AU  - Florio, Marta
AU  - Namba, Takashi
AU  - Pääbo, Svante
AU  - Hiller, Michael
AU  - Huttner, Wieland B.
TI  - A single splice site mutation in human-specific <em>ARHGAP11B</em> causes basal progenitor amplification
AID  - 10.1126/sciadv.1601941
DP  - 2016 Dec 01
TA  - Science Advances
PG  - e1601941
VI  - 2
IP  - 12
4099  - http://advances.sciencemag.org/content/2/12/e1601941.short
4100  - http://advances.sciencemag.org/content/2/12/e1601941.full
SO  - Sci Adv2016 Dec 01; 2
AB  - The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex.