Paired involvement of human-specific Olduvai domains and NOTCH2NL genes in human brain evolution

Bibliographic Collection: 
APE, CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Fiddes, Ian T; Pollen, Alex A; Davis, Jonathan M; Sikela, James M
Year of Publication: 2019
Journal: Human Genetics
Volume: 138
Issue: 656
Pagination: 1-7
Date Published: 05/2019
Publication Language: eng

Sequences encoding Olduvai (DUF1220) protein domains show the largest human-specific increase in copy number of any coding region in the genome and have been linked to human brain evolution. Most human-specific copies of Olduvai (119/165) are encoded by three NBPF genes that are adjacent to three human-specific NOTCH2NL genes that have been shown to promote cortical neurogenesis. Here, employing genomic, phylogenetic, and transcriptomic evidence, we show that these NOTCH2NL/NBPF gene pairs evolved jointly, as two-gene units, very recently in human evolution, and are likely co-regulated. Remarkably, while three NOTCH2NL paralogs were added, adjacent Olduvai sequences hyper-amplified, adding 119 human-specific copies. The data suggest that human-specific Olduvai domains and adjacent NOTCH2NL genes may function in a coordinated, complementary fashion to promote neurogenesis and human brain expansion in a dosage-related manner.

DOI: 10.1007/s00439-019-02018-4