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

Abstract

ing up empty handed [Konopka and Geschwind, 2010]. Therefore, the contribution of potential genomic mechanisms to human brain uniqueness still remains mostly unknown. In a recent report, Zhang et al. [2011] attempted to address this feature of human brain evolution by examining the role of genes expressed in the fetal human brain. Until the recent availability of gene expression datasets from human fetal brain, all studies of genomics within the human brain have utilized adult tissue samples. Since the period of prenatal development is critical for normal cognitive functioning (as evidenced by the existence of numerous neurodevelopmental disorders like autism), analysis of fetal brain gene expression should likely provide key insights into human cognition where adult gene expression falls short. Zhang et al. [2011] used a combination of published microarray data, unpublished RNA sequencing data, and expressed sequence tag data in their analyses. They focused specifically on what they call ‘young’ genes, or those genes that have arisen in the primate lineage. By highlighting the young genes in the transcriptome data, the authors uncovered important results regarding human brain evolution. The genome revolution that included sequencing of the human and chimpanzee genomes promised to provide answers to how humans evolved their unique cognitive abilities. However, comparisons at the DNA level in protein-coding regions of the genome among primates have revealed few clues as to the molecular mechanisms underlying human brain evolution. 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. In addition, gene expression in the human brain has been found to be the most evolutionarily constrained compared to other tissues [Wang et al., 2007; Brawand et al., 2011], consistent with investigations into evidence for accelerated evolution among human brain genes comPublished online: March 6, 2012