Human Brain Evolution: Harnessing the Genomics (R)evolution to Link Genes, Cognition, and Behavior

Abstract

The evolution of the human brain has resulted in numerous specialized features including higher cognitive processes, such as language. The combination of our newfound communication expertise together with the process of transgenerational evolution at the epigenetic level has led to an exponential increase in human knowledge and abilities. In balance with these beneficent attainments though, the human brain has also acquired vulnerabilities to neuropsychiatric and neurodegenerative diseases, which reflect genetic and environmental factors. To understand the mechanisms of this disease susceptibility, a deeper appreciation of the developmental processes and their relationship to underlying features of brain evolution will be necessary. Knowledge of whole genome sequence and structural variation via high throughput sequencing technology provides an unprecedented opportunity to view human evolution at high resolution. However, phenotype discovery is a critical component of these endeavors and the use of non-traditional model organisms will also be critical for piecing together a complete picture. Ultimately, the union of developmental studies of the brain with studies of unique phenotypes in a myriad of species will result in a more thorough model of the groundwork the human brain built upon. Furthermore, these integrative approaches should provide important insights into human diseases.

Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain

“…Over 100 different anatomical structures are connected by billions of neurons and glia into a functional network that regulates tissue homeostasis throughout the body while also determining our cognitive state (Nolte, 2009). Functionally distinct anatomical regions have evolved in a species-specific manner, giving rise to the defining physical and cognitive features that separate humans from other species (Konopka and Geschwind, 2010). Microarray analyses on distinct regions of the human brain have demonstrated that gene expression profiles vary significantly across adult brain structures (Colantuoni et al, 2011;Hawrylycz et al, 2012;Kang et al, 2011).…”

Decoding human gene expression signatures in the brain

“…A number of studies have uncovered that the pattern of gene co-expression is a critical mediator of brain function and exhibits significantly different patterns across species. 43 Gene pairs that have strong co-expression relationships are more likely to be functional together; therefore such analysis of co-expression networks in the brain among primates has proven informative. For example, weighted gene co-expression network analysis has been used to identify human-specific networks of gene expression compared with chimpanzees.…”

The Fetal Brain Provides a Raison d’être for the Evolution of New Human Genes

“…ing up empty handed [Konopka and Geschwind, 2010]. Therefore, the contribution of potential genomic mechanisms to human brain uniqueness still remains mostly unknown.…”

“…As previously predicted [King and Wilson, 1975], we are therefore left with differential regulation of gene expression in the human lineage as a potential major evolutionary force driving human cognition. The recent advent of microarrays and next generation sequencing technologies have allowed us to compare gene expression in the brains of humans and other species at a genomewide level [Konopka and Geschwind, 2010]. However, the identification of a few hundred genes differentially expressed between human and non-human primate brain [Caceres et al, 2003] is unlikely in itself to explain the higher cognition in humans.…”

“…The inclusion of gene expression data from developing human brain was critical for the study by Zhang et al [2011], as sim-ilar analyses in adult human brain did not find evidence for accelerated evolution [Wang et al, 2007;Konopka and Geschwind, 2010]. Two other recent papers have demonstrated how developmental trajectories lead to important changes in human brain gene expression patterns [Colantuoni et al, 2011;Kang et al, 2011], and provide, for the first time, gene expression data in the human brain throughout the entire lifespan, including fetal development.…”