Cognitive domains function complementation by NTNG gene paralogs

Abstract

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 [1]. 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.

Cognitive endophenotypes of modern and extinct hominins associated with NTNG gene paralogs

“…Here we have described how a pair of twin genes got themselves involved into the human cognitive functioning believed to be emerged in a primordial state in primitive vertebrates prior to the first recorded gene duplication. Subsequent process of the function specialisation made NTNG paralogs to subfunctionalise into distinct cognitive domains in a complementary manner [53].…”

“…ROIs of 3 of them (rs2218404, rs1373336 and rs2274855) underwent an AE from chimpanzee to human when compared to New World monkeys to apes (marmoset-chimpanzee) path (Figure 2C and 3C). Two of them affect IQ in humans (rs2218404 -VC and rs2274855 -WM, Figure 1B-1 and B-2) while being located within the vicinity of exon 5 (2,275 nu downstream and 15 nu upstream, respectively) -a part of the lowest percent identity coding DNA among the NTNG gene paralogs [53]. Presence of the evolutionary accelerated regions within the NTNG genes non-coding areas underscores them as contributors to the human-specific traits along with other genes [54].…”

Behavior Variability of a Conditional Gene Knockout Mouse as a Measure of Subtle Phenotypic Trait Expression. The Case of Mouse Executive Function Distortion

“…Previously, we have shown that a pair of brain vertebrate-specific presynaptically expressed gene paralogs, NTNG1/2, is functionally characterised by antagonistic pleiothropy (19), and associated with the human IQ scores (20). including the task learning (spatial 1) for Table 2-1 (ST2-1)).…”