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

• Published in: Human genetics Vol. 138; no. 7; pp. 715 - 721
• Main Authors: Fiddes, Ian T., Pollen, Alex A., Davis, Jonathan M., Sikela, James M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2019; Springer; Springer Nature B.V
• Subjects: Biological Evolution; Biomedical and Life Sciences; Biomedicine; Brain; Brain - growth & development; Brain - metabolism; Carrier Proteins - genetics; Copy number; Cortex; Evolution; Evolutionary genetics; Gene Function; Genes; Genetic aspects; Genome, Human; Genomes; Genomics; Human evolution; Human Genetics; Humans; Metabolic Diseases; Molecular Medicine; Neural coding; Neurogenesis; Original Investigation; Phylogeny; Protein Domains; Receptor, Notch2 - genetics
• ISSN: 0340-6717; 1432-1203; 1432-1203
• DOI: 10.1007/s00439-019-02018-4

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.