Dec 17, 2015

COGNITIVE ENDOPHENOTYPES OF MODERN AND EXTINCT HOMININS ASSOCIATED WITH NTNG GENE PARALOGS

BioRxiv : the Preprint Server for Biology
Pavel ProsselkovShigeyoshi Itohara

Abstract

A pair of gene paralogs, NTNG1 and NTNG2, contributes to the Intellectual Quotient (IQ) test scores in a complementary manner. Single nucleotide polymorphisms (SNPs) of NTNG1 are associated with attenuated verbal comprehension (VC) or processing speed (PS) while NTNG2 SNPs affect working memory (WM) and perceptual organization (PO) forming cognitive endophenotypes in healthy and schizophrenia (SCZ) affected human subjects. Regions of interest (ROIs), defined as 21 nucleotide (nu) long loci embedding the IQ affecting mutation alleles (VC and WM/PO), underwent dramatic evolutionary changes from mice through primates to hominin genes at the accelerated rates. Mutation alleles associated with the higher VC and WM IQ scores are found in the genomes of extinct hominins of Neolithic times, however, lower WM scores associated allele is also detectable in Mesolithic hunters genomes. Protein sequence of NTNG1 is 100% conserved among the archaic and modern extinct hominins while NTNG2 underwent a recent selection sweep encoding a primate-specific S371A/V (~50,000 yrs BC), and a modern human (5,300 yrs BC) T346A substitutions. We show that a 500 mln yrs old genomic duplication of a synapse primordial gene of an urochordate provided a subst...Continue Reading

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Mentioned in this Paper

Vertebrates
Memory, Short-Term
Gene Polymorphism
Ntng1
Genome
Genes
Schizophrenia
Intelligence
RAD51B gene
NTNG2 protein, human

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