Science + Technology

UCLA Geneticists Aim to Unravel Where Chimp and Human Brains Diverge

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Sixmillion years ago, chimpanzees and humans diverged from a common ancestor andevolved into unique species. Now UCLA scientists have identified a new way topinpoint the genes that separate us from our closest living relative and makeus uniquely human. The Proceedings of the National Academy of Sciences reportsthe study in its Nov. 13 online edition.

"We share morethan 95 percent of our genetic blueprint with chimps," explained Dr. Daniel Geschwind, principal investigator and Gordon and Virginia MacDonald Distinguished Professor ofHuman Genetics at the David Geffen School of Medicine. "What sets usapart from chimps are our brains: homo sapiens means 'the knowing man.'"

Duringevolution, changes in some genes altered how the human brain functions, henoted.

"Ourresearch has identified an entirely new way to identify those genes in the smallportion of our DNA that differs from the chimpanzee's,"Geschwind said.

Byevaluating the correlated activity of thousands of genes, the UCLAteam identified not just individual genes, but entire networks ofinterconnected genes whose expression patterns within the brains of humansvaried from those in the chimpanzee. Gene expression is the process by which agene's DNA sequence is converted into cellular proteins.

"Genesdon't operate in isolation — each functions within a system of related genes,"said first author Michael Oldham, UCLA genetics researcher. "If we examinedeach gene individually, it would be similar to reading every fifth word in aparagraph — you don't get to see how each word relates to the other. So insteadwe used a systems biology approach to study each gene within its context."

Thescientists identified networks of genes that correspond to specific brainregions. When they compared these networks between humans and chimps, theyfound that the gene networks differed the most widely in the cerebral cortex —the brain's most highly evolved region, which is three times larger in humansthan chimps.

Secondly,the researchers discovered that many of the genes that play a central role incerebral cortex networks in humans — but not in the chimpanzee — also showsignificant changes at the DNA level.

 "Whenwe see alterations in a gene network that correspond to functional changes inthe genome, it implies that these differences are very meaningful," said Oldham. "This finding supports the theory that variationsin the DNA sequence contributed to human evolution."

Relying on a new analyticalapproach developed by corresponding author Steve Horvath, UCLA associateprofessor of human genetics and biostatistics, the UCLA team used data from DNAmicroarrays — vast collections of tiny DNA spots — tomap the activity of virtually every gene in the genome simultaneously. Bycomparing gene activity in different areas of the brain, the team identifiedgene networks that correlated to specific brain regions. Then they compared thestrength of these correlations between humans and chimps.

Many of the human-specific gene networks identified by the scientistsrelated to learning, brain cell activity and energy metabolism.  

"If you view the brain as the body's engine, our findings suggestthat the human brain is like a 12-cylinder engine, while the chimp brain ismore like a 6-cylinder," explained Geschwind. "It'spossible that our genes adapted to allow our brains to increase in size,operate at different speeds, metabolize energy faster and enhance connectionsbetween brain cells across different brain regions."  

Future UCLAstudies will focus on linking the expression of evolutionary genes to specificregions of the brain, such as those that regulate language, speech and otheruniquely human abilities.

The studywas supported by the James S. McDonnell Foundation, the NationalInstitute of Neurological Disorders and Stroke, and the National Institute ofMental Health.

-UCLA-

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