Wednesday, September 20, 2006

RNA gene, HAR1, involved in cortical development, changed in humans

The authors suggest that we should be looking at the 98.5% of the genome that is non-coding to look for signatures of selection in humans. They find several regions that they call HAR (human accelerated region). They find HAR1 in particular that is very changed in humans compared to other primates and mammals. They also provide some functional data as to how this gene is expressed in the neocortex during the very early stages of development.

They also find that the substitutions in HAR1 ( and most of all HAR) are all A or T to C or G, so called weak-to-strong changes, that "strengthen RNA helices" and perhaps "increase gene stability and increased expression levels".

Here the Wikipedia entry on RNA genes.

An RNA gene expressed during cortical development evolved rapidly in humans

Katherine S. Pollard, Sofie R. Salama, Nelle Lambert, Marie-Alexandra Lambot, Sandra Coppens, Jakob S. Pedersen, Sol Katzman, Bryan King, Courtney Onodera, Adam Siepel, Andrew D. Kern, Colette Dehay, Haller Igel, Manuel Ares, Jr, Pierre Vanderhaeghen and David Haussler

Nature 443, 167-172(14 September 2006)

Abstract: 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.

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