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Hum Genet. 2019 May 13. doi: 10.1007/s00439-019-02018-4. [Epub ahead of print]

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

Author information

1
10X Genomics, Pleasanton, CA, USA.
2
Department of Neurology and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research at the University of California, San Francisco, San Francisco, CA, USA.
3
Department of Biochemistry and Molecular Genetics, Human Medical Genetics and Genomics Program and Neuroscience Program, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
4
Department of Biochemistry and Molecular Genetics, Human Medical Genetics and Genomics Program and Neuroscience Program, University of Colorado School of Medicine, Aurora, CO, 80045, USA. james.sikela@ucdenver.edu.

Abstract

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.

PMID:
31087184
DOI:
10.1007/s00439-019-02018-4

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