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New research backs theory that genetic 'switches' play big role in human evolution
Date:6/19/2013

doing so, switch genes on and off.

Among the findings, the study reports that when compared with protein coding genes, binding site DNA shows close to three times as many "weakly deleterious mutations," that is, mutations that may weaken or make an individual more susceptible to disease, but are generally not severe. Weakly deleterious mutations exist in low frequencies in a population and are eventually weeded out over time. These mutations are responsible for many inherited human diseases.

While genes generally tend to resist change, a mutation occasionally leads to a favorable trait and increases across a population; this is called positive selection. By contrast, "transcription factor binding sites show considerable amounts of positive selection," said Arbiza, with evidence for adaptation in binding sites that regulate genes controlling blood cells, brain function and immunity, among others.

"The overall picture shows more evolutionary flexibility in the binding sites than in protein coding genes," said Siepel. "This has important implications for how we think about human evolution and disease."

This is one of the first studies to combine recent data that identifies transcription factor binding sites, data on human genetic variation and genome comparisons between humans and apes. A new computational method called INSIGHT (Inference of Natural Selection from Interspersed Genomically coHerent elemenTs), designed by Ilan Gronau, a postdoctoral researcher in Siepel's lab and a co-author of the study, allowed the scientists to integrate these diverse data types and find evidence of natural selection in the regulatory DNA.

"Transcription factor binding sites are probably the regulatory elements we know the most about," said Arbiza. "If you want to understand evolution of gene expression regulation, that's a good starting point."

INSIGHT may now be used by other researchers for analyzing other short regulatory DNA
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Contact: John Carberry
johncarberry@cornell.edu
607-255-5353
Cornell University
Source:Eurekalert

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