An RNA gene expressed during cortical development evolved rapidly in humans

The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these ‘human accelerated regions’, HAR1, is part of a novel RNA gene ( HAR1F ) that is expressed specifically in Cajal–Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal–Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology. The human factor What makes humans unique? A comparative genetics approach to this question reveals a candidate gene for a part in bestowing 'humanness'. Interestingly, the gene is expressed during embryonic development of the neocortex, the site of many of the brain's most sophisticated processes. The gene emerged from a scan for non-coding genomic regions that remained mostly unchanged up to the point of the chimp/human evolutionary split, but which then underwent accelerated evolution in humans. One of the most rapidly evolving genomic regions in the human lineage corresponds to a previously unstudied RNA gene, dubbed HAR1F . Gene expression studies then showed that HAR1F is active in cells called Cajal-Retzius neurons during the crucial period of gestation, when many of the nerve cells of the neocortex are establishing their functions within the brain. One of the most rapidly evolving genomic regions in the human lineage corresponds to a previously unstudied RNA gene, called HAR1. Based on expression studies, it is likely that HAR1 likely plays an important role in brain biology.