October 5, 2008

Gene Activity Makes the Difference in Development of Human Qualities

By Ehrenberg, Rachel

Genes & Cells 'Junk DNA' helps to distinguish people from other primates

Genes alone don't make the man - after all, humans and chimps share roughly 98 percent of their DNA. But where, when and how much genes are turned on may be essential in setting people apart from other primates.

A stretch of human DNA inserted into mice embryos revs up gene activity in developing thumbs, toes and limbs. But the chimp and rhesus macaque version of that DNA spurs only faint activity in the limbs, scientists report in the Sept. 5 Science.

The research supports the notion that changes in gene regulation- rather than changes in the genes themselves-were key evolutionary steps in humans' ability to use fire, invent wheels and ponder existential questions, like what distinguishes people from their primate cousins.

"We're trying to find out what makes us human," says James Noonan, now at Yale University, who led the study with colleagues from Lawrence Berkeley National Laboratory, the Genome Institute of Singapore, Caltech and the United Kingdom's Medical Research Council. "We know that the things that make us human biologically are encoded in there somewhere."

Noonan and colleagues combed through vast regions of human DNA that do not contain code for making proteins. Formerly dissed as "junk DNA," sections of these nongene regions are now known to play a regulatory role, dialing down or cranking up the activity of actual genes.

Like electrical wiring in a house, genes maybe turned on in many places at once, even though the genes might only be needed in one area, such as the eye, comments Francesca Mariani of the Broad Center for Regenerative Medicine and Stem Cell Research at the University of Southern California in Los Angeles. So while the new study can't say what these regulatory changes might do in a human embryo, "this does show how a few small changes could make a big difference," she says.

The researchers identified a DNA region made up of 546 base pairs, or "letters" of code, which have barely changed during the evolution of backboned creatures. But that region has accumulated 16 changes since the ancestors of chimps and humans split, some 6 million years ago. Thirteen of these changes were clustered within an 81-base-pair region, the researchers report.

To see the effects of the changes, the researchers inserted the human, chimp and rhesus macaque versions of the region into mouse embryos. All turned on genes in tne developing ear and eye, and in the embryonic gills, or pharyngeal arches.

But the human version dramatically boosted the activity of genes in the mouse's primordial thumb, forelimb, hind limb and toe, the researchers found.

A stretch of human DNA, when inserted Into a mouse embryo, cranks up gene activity In the developing thumb (shown in blue).

Copyright Science Service, Incorporated Sep 27, 2008

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