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 tests. Both NTNG paralogs are associated with autism spectrum disorder, bipolar disorder and schizophrenia, with unique non-overlapping segregation among the other cognitive disorders, emphasizing an evolutionary gain-dependent link between advanced cognitive functions and concomitant neurocognitive pathologies. We revealed complementary expression and transcriptome composition of the paralogs within the human brain explaining the observed phenomena of NTNG1 and NTNG2 functional complementarity. The gene paralogs expression levels undergo age-dependent and brain area-specific modalities over the almost entire human lifespan. It has also been reported that NTNG1 contains anthropoid-specific constrained regions, and both genes contain non-coding conserved sequences that underwent accelerated evolution in human. NTNG paralogs SF perturbates ‘structure drives function’ concept at protein and gene levels. We suggest that the paralogs function diversification forms a so-called ‘Cognitive Complement’, as an end product of gene duplication and subsequent cognitive subfunction bifurcation among the NTNG gene duplicates.
Supplementary Material for this publication: Prosselkov-2016-BGG-1-105-SM