Genetic mapping and evolutionary analysis\xa0of human-expanded cognitive networks

Yongbin Wei,Kyoko Watanabe,Todd M Preuss,Danielle Posthuma,James K Rilling,Siemon C De Lange,Martijn P Van Den Heuvel,Longchuan Li,Jeanne E Savage,Dirk Jan Ardesch,Lianne H Scholtens,Philip R Jansen

doi:10.1038/s41467-019-12764-8

Abstract

Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain. Here we show that the rapid evolutionary cortical expansion of cognitive networks in the human brain, and most pronounced the DMN, runs parallel with high expression of human-accelerated genes (HAR genes). Using comparative transcriptomics analysis, we present that HAR genes are differentially more expressed in higher-order cognitive networks in humans compared to chimpanzees and macaques and that genes with high expression in the DMN are involved in synapse and dendrite formation. Moreover, HAR and DMN genes show significant associations with individual variations in DMN functional activity, intelligence, sociability, and mental conditions such as schizophrenia and autism. Our results suggest that the expansion of higher-order functional networks subserving increasing cognitive properties has been an important locus of genetic changes in recent human brain evolution.

Highlights

Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain
We identified genes commonly expressed in brain areas using the Genotype-Tissue Expression (GTEx) database, selecting 2979 genes significantly more expressed in brain tissues compared to other available body sites (q < 0.05, FDR corrected; one-sided twosample t-test; referred to as BRAIN genes); 415 genes (24.3%) out of the full set of 1711 human accelerated regions (HAR) genes were observed to be significantly more expressed in brain tissues, a set on referred to as HAR-BRAIN genes
In addition to common variations indicated by GWAS, we further examined the enrichment of HAR/HAR-BRAIN and DMN genes in rare variants of brain disorders using the NPdenovo database[35]

Summary

Introduction

Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain. The human brain is capable of supporting a wide range of complex cognitive abilities, more so than other highly developed and intelligent great apes, such as the chimpanzee, one of our closest living evolutionary relatives with which we share the majority of our genetic material[1] This distinction in cognitive abilities is commonly believed to be associated with the rapid expansion of multimodal association areas and their structural and functional connections in the human brain[2,3,4], with cognitive functional networks, such as the frontoparietal network, salience network, and default-mode network (DMN), playing an essential role in higher-order brain functions[5,6,7]. We provide further evidence of HAR and DMN genes to be important in human cognitive functioning, social behavior, and mental disorders, such as autism and schizophrenia

Methods

Results

Conclusion