A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

作者：Florio Marta; Namba Takashi; Paeaebo Svante; Hiller Michael; Huttner Wieland B

来源：Science Advances, 2016, 2(12): e1601941.

DOI：10.1126/sciadv.1601941

<jats:p>The gene <jats:italic>ARHGAP11B</jats:italic> promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of <jats:italic>ARHGAP11A</jats:italic>, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in <jats:italic>ARHGAP11B</jats:italic> 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 <jats:italic>ARHGAP11B</jats:italic> 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.</jats:p>

• 出版日期2016-12