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Human Evolution, Genome Style

16 August 2006 (All day)
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Todd Preuss/Yerkes Primate Research Center

Brainpower boost.
An RNA gene is implicated in the evolution of the human brain (top), which is bigger and more complex than a chimp's (bottom).

Genomes have proven fertile ground for clues to what makes us different from our primate cousins. Now, geneticists have unearthed a several stretches of DNA that may underlie our evolution. One seems to be involved in the most momentous innovation: the rapid expansion of the human cerebral cortex, the brain region responsible for higher cognition. Yet most of this DNA doesn't encode proteins, providing further evidence that changes in gene regulation have been as important, if not more important, as protein changes have been in helping humans evolve.

Over the past 5 years, researchers have sequenced the genomes of dozens of animals, including humans, chimpanzees, mice, fish, and chickens. By lining up comparable sections of these genomes and counting up the differences in the DNA sequences, researchers have begun to reconstruct our genetic history. For the most part, researchers have focused on genetic changes--such as mutations in protein-coding genes, gene duplications, and alterations in gene expression--as key to the evolution of humans. But with ever more sophisticated computer software and hardware, they have begun to look at the DNA in between genes as well.

Katherine Pollard, now a biostatistician at the University of California, Davis, and her colleagues tapped this software, which she developed, to look for genetic novelties in humans. She found 49 regions where the DNA was stable in all the mammalian genomes examined except for the human genome, indicating that the sequences had undergone rapid evolution in the human lineage. One called HAR1 had 18 base changes over a 118-base stretch, where less than one was expected during the normal course of evolution. About 96% of those regions, including HAR1, lack any protein-coding genes.

The HAR1 region stretches across part of two genes that code for RNA. University of California, Santa Cruz, cell biologist Sofie Salama, working with Pierre Vanderhaeghen, a neuroscientist at the University of Brussels, Belgium, has found one of these genes, HAR1F, is quite active in the 2-month- to 5-month-old human embryo. The HAR1F RNA is present in cells that help organize the human cortex into layers in conjunction with proteins key to that organization, Pollard and her colleagues report online today in Nature. Because RNA can play a role in gene regulation and protein function, Pollard and her colleagues suspect HAR1F RNA may help control the production of proteins involved in organizing the cerebral cortex.

The discovery of the RNA gene "opens up a new area of genomic factors that haven't traditionally been looked at," says James Sikela, a genome researcher at the University of Colorado Health Science Center in Denver. The work "is an example of the utility of these new genome sequences."

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