Rapid Evolution Of Non-Coding DNA Since The Split Between Human And Chimp Genome (7/18/2007)

A difference of only a few percent in DNA sequence is thought to separate the human and chimp genomes. New research published in Genome Biology identifies the subset of sequences that may have driven the evolution of our two species.

The researchers propose that the key changes lie in regions of our genome that control the activity of genes. It is managers of the genome, rather than the workforce, that have been most responsible for differences between chimps and humans.

A team led by scientists from the Wellcome Trust Sanger Institute looked at DNA elements called conserved non-coding regions (CNCs) in human, chimpanzee and macaque genomes. CNCs are stretches of DNA that are similar in different species but do not contain code for making proteins.

The team looked at how CNCs had changed since the split of human and chimp lineages some six million years ago. Remarkably, they showed that a subset of CNCs is undergoing accelerated evolutionary changes: this set they called ANCs (for accelerated non-coding sequences) and they showed that ANCs are mutating at a rate sevenfold higher than the remainder of the genome.

"We searched more than 300,000 CNCs identified in the human genome," explained Dr Manolis Dermitzakis, Project Leader at the Wellcome Trust Sanger Institute, "and found 1356 that were diverging more rapidly in our DNA than in chimp DNA. These sequences mark human-specific changes."

"The question for us was: 'Do these ANCs have a biological significance?'."

The team used two tests to show that the variation was of consequence. First, they compared ANCs with other regions of the human genome and showed that many ANCs were evolving more rapidly than the genome bulk. This shows that evolutionary pressure is acting upon ANCs specifically and the changes are not simply due to natural variation.

If these changes are driven by evolution, what might be the consequences for gene activity? Variation in our genome has been mapped through the HapMap Project and cells used for that Project can be used to measure gene activity.

The team studied the activity of genes located close to ANCs in 210 samples from the HapMap. They found that DNA sequence variation in an ANC was often associated with an alteration of gene activity in the HapMap samples.

"The HapMap samples provide our strongest evidence that ANCs have real biological meaning for human gene activity," commented Christine Bird, first author on the study, from the Sanger Institute. "These are sequences whose evolution appears to be inextricably linked with an alteration in gene activity."

"We show that evolution of non-coding DNA occurs at an accelerated rate and that it could make a major contribution to evolution of our species."

The presence of ANCs in the human genome suggests that the evolution of noncoding DNA contributes substantially to species differentiation. The results suggest that ANCs have not only contributed to evolutionary change along the human lineage since the time of the human-chimpanzee common ancestor, but also that some have contributed to recent differentiation between human populations. The ANCs identified in this study can serve as a baseline for the elucidation of biological processes in non-coding DNA that contribute to species differentiation.

Note: This story has been adapted from a news release issued by the Sanger Institute

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