Abstract
Olduvai protein domains, encoded primarily by NBPF genes, have been linked to both human brain evolution and cognitive diseases such as autism and schizophrenia. There are six primary domains that comprise the Olduvai family: three conserved domains (CON1-3) and three human lineage-specific domains (HLS1-3), which typically occur as a triplet (HLS1, HLS2 and HLS3). Herein, we present the solution NMR assignment of the backbone chemical shifts of the separate HLS1, 2 and 3 domains of NBPF15. Our data suggest that there is no change in the structure of the separate domains when compared to the full-length triplet (HLS1–HLS2–HLS3). We also demonstrate that there is no direct interaction between the three domains.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bleness MS, Dickens CM, Dumas LJ et al (2012) Evolutionary history and genome organization of DUF1220 protein domains. G3 (Bethesda) G3(2):977–986. https://doi.org/10.1534/g3.112.003061
Cavanagh J (2007) Protein NMR spectroscopy: principles and practice. Academic Press, Amsterdam
Davis JM, Searles VB, Anderson N et al (2014) DUF1220 dosage is linearly associated with increasing severity of the three primary symptoms of autism. PLoS Genet 10:e1004241. https://doi.org/10.1371/journal.pgen.1004241
Davis JM, Searles Quick VB, Sikela JM (2015a) Replicated linear association between DUF1220 copy number and severity of social impairment in autism. Hum Genet 134:569–575. https://doi.org/10.1007/s00439-015-1537-6
Davis JM, Searles VB, Anderson N et al (2015b) DUF1220 copy number is linearly associated with increased cognitive function as measured by total IQ and mathematical aptitude scores. Hum Genet 134:67–75. https://doi.org/10.1007/s00439-014-1489-2
Davis JM, Heft I, Scherer SW, Sikela JM (2019) A third linear association between olduvai (DUF1220) copy number and severity of the classic symptoms of inherited autism. Am J Psychiatry. https://doi.org/10.1176/appi.ajp.2018.18080993
Delaglio F, Grzesiek S, Vuister GW et al (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277–293
Dumas L, Sikela JM (2009) DUF1220 domains, cognitive disease, and human brain evolution. Cold Spring Harb Symp Quant Biol 74:375–382. https://doi.org/10.1101/sqb.2009.74.025
Dumas LJ, O’Bleness MS, Davis JM et al (2012) DUF1220-domain copy number implicated in human brain-size pathology and evolution. Am J Hum Genet 91:444–454. https://doi.org/10.1016/j.ajhg.2012.07.016
Fiddes IT, Pollen AA, Davis JM, Sikela JM (2019) Paired involvement of human-specific Olduvai domains and NOTCH2NL genes in human brain evolution. Hum Genet 138:1–7. https://doi.org/10.1007/s00439-019-02018-4
Hyberts SG, Milbradt AG, Wagner AB et al (2012a) Application of iterative soft thresholding for fast reconstruction of NMR data non-uniformly sampled with multidimensional Poisson Gap scheduling. J Biomol NMR 52:315–327. https://doi.org/10.1007/s10858-012-9611-z
Hyberts SG, Milbradt AG, Wagner AB et al (2012b) Application of iterative soft thresholding for fast reconstruction of NMR data non-uniformly sampled with multidimensional poisson gap scheduling. J Biomol NMR 52:315–327. https://doi.org/10.1007/s10858-012-9611-z
Ikura M, Kay LE, Bax A (1990) A novel approach for sequential assignment of 1H, 13C, and 15 N spectra of proteins: heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin. Biochemistry 29:4659–4667
Keeney JG, Davis JM, Siegenthaler J et al (2014) DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates. Brain Struct Funct 220(5):3053–3060. https://doi.org/10.1007/s00429-014-0814-9
Lee W, Tonelli M, Markley JL (2015) NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics 31:1325–1327. https://doi.org/10.1093/bioinformatics/btu830
Popesco MC, Maclaren EJ, Hopkins J et al (2006) Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains. Science 313:1304–1307. https://doi.org/10.1126/science.1127980
Searles Quick VB, Davis JM, Olincy A, Sikela JM (2015) DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases. Transl Psychiatry 5:e697. https://doi.org/10.1038/tp.2015.192
Sikela JM, Searles Quick VB (2018) Genomic trade-offs: are autism and schizophrenia the steep price of the human brain? Hum Genet 137:1–13. https://doi.org/10.1007/s00439-017-1865-9
Sikela JM, van Roy F (2017) A proposal to change the name of the domain to the Olduvai domain. F1000Research 6:1285. https://doi.org/10.12688/f1000research.13586.1
Vandepoele K, Van Roy N, Staes K et al (2005) A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution. Mol Biol Evol 22:2265–2274. https://doi.org/10.1093/molbev/msi222
Vranken WF, Boucher W, Stevens TJ et al (2005) The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins Struct Funct Bioinform 59:687–696. https://doi.org/10.1002/prot.20449
Acknowledgements
The authors thank David Jones and Shaun Bevers (University of Colorado, Denver) for their help and support. This project is funded by a University of Colorado start-up Grant the to B.V. and NIH R01 Grant MH108684 to J.S.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Accession numbers
The chemical shift assignments for HLS1 (BMRB 27569), HLS2 (BMRB 27533) and HLS3 (BMRB 27775) have been deposited in the Biological Magnetic Resonance Data Bank.
Rights and permissions
About this article
Cite this article
Issaian, A., Schmitt, L., Born, A. et al. Solution NMR backbone assignment reveals interaction-free tumbling of human lineage-specific Olduvai protein domains. Biomol NMR Assign 13, 339–343 (2019). https://doi.org/10.1007/s12104-019-09902-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12104-019-09902-0