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Mice, men make livers differently

prise, they found that most of the binding sitesbetween 41 percent and 89 percent, depending on the transcription factorwere in different locations in humans and mice.

"The number of genes with the identical regulation in both species was very, very small," Fraenkel said.

Before they began, the researchers expected to see some differences in gene regulation between mice and humans, because the human liver has evolved to process cooked food, said Fraenkel. However, the magnitude of change was much higher than they anticipated.

Fraenkel speculated that the changes accumulated without having much of an effect on gene expression. Unless the location of binding sites affects gene expression, it is not under any natural selection pressure.

All of that meaningless variation makes it harder to identify the small number of genes where binding site migrations do have an evolutionary impact, because they are being drowned out by all the insignificant changes, Fraenkel said. In future studies, the research team plans to investigate why some genes binding sites are conserved over time while others shift.

"We want to understand whats special about those genes," Fraenkel said.

Fraenkel said the results should provide guidance for researchers who study mice to better understand human biology. "To get the most out of mice for biomedical research we need to fully map out the regulation in both organisms," he said.


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Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
21-May-2007


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