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COGNITIVE DOMAINS FUNCTION COMPLEMENTATION BY NTNG GENE PARALOGS

By Pavel Prosselkov, Denis Polygalov, Qi Zhang, Thomas J. McHugh, Shigeyoshi Itohara

Posted 17 Dec 2015
bioRxiv DOI: 10.1101/034645 (published DOI: 10.15761/BGG.1000105)

Gene duplication was proposed by S.Ohno (1) as a key mechanism of a novel gene function evolution. A pair of gene paralogs, NTNG1 and NTNG2, sharing identical gene and protein structures and encoding similar proteins, forms a functional complement subfunctionalising (SF) within cognitive domains and forming cognitive endophenotypes, as detected by Intellectual Quotient (IQ) tests (2). Both NTNG paralogs are associated with autism spectrum disorder (ASD), bipolar disorder (BD) and schizophrenia (SCZ), with unique non-overlapping segregation among the other 15 cognitive disorders (CD), emphasizing an evolutionary gain-dependent link between advanced cognitive functions and concomitant neurocognitive pathologies. Complementary expression and human brain transcriptome composition of the paralogs explains the observed phenomena of their functional complementarity. The lowest identity among NTNGs is found in a middle of encoded by them proteins designated as uknown (Ukd) domain. NTNG1 contains anthropoid-specific constrained regions, and both genes contain non-coding conserved sequences underwent accelerated evolution in human. NTNG paralogs SF perturbates 'structure drives function' concept at protein and gene levels. The paralogs function diversification forms a so-called 'Cognitive Complement (CC)', a product of gene duplication and subsequent cognitive subfunction bifurcation among the NTNG gene duplicates.

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