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Most human-chimp differences due to gene regulation ?not genes

The vast differences between humans and chimpanzees are due more to changes in gene regulation than differences in individual genes themselves, researchers from Yale, the University of Chicago, and the Hall Institute in Parkville, Victoria, Australia, argue in the 9 March 2006 issue of the journal Nature.

The scientists provide powerful new evidence for a 30-year-old theory, proposed in a classic paper from Mary-Claire King and Allan Wilson of Berkeley. That 1975 paper documented the 99-percent similarity of genes from humans and chimps and suggested that altered gene regulation, rather than changes in coding, might explain how so few genetic changes could produce the wide anatomic and behavioral differences between the two.

Using novel gene-array technology to measure the extent of gene expression in thousands of genes simultaneously, this study shows that as humans diverged from their ape ancestors in the last five million years, genes for transcription factors -- which control the expression of other genes -- were four times as likely to have changed their own expression patterns as the genes they regulate.

Because they influence the activity of many "downstream" genetic targets, small changes in the expression of these regulatory genes can have an enormous impact.

"When we looked at gene expression, we found fairly small changes in 65 million years of the macaque, orangutan, and chimpanzee evolution," said study author Yoav Gilad, Ph.D., assistant professor of human genetics at the University of Chicago, "followed by rapid change, along the five million years of the human lineage, that was concentrated on these specific groups of genes. This rapid evolution in transcription factors occurred only in humans."

"For 30 years scientists have suspected that gene regulation has played a central role in human evolution," said Kevin White, Ph.D., associate professor of genetics and ecology and evolution at Yale and senior a
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Source:University of Chicago Medical Center


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