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Fast-mutating DNA sequences shape early development; guided evolution of uniquely human traits
Date:11/10/2013

, the research team identified more than 2,600 HARs. Then, they created a program called EnhancerFinder to whittle down that list to just the HARs were likely to be enhancers.

"EnhancerFinder is a machine-learning algorithm that takes in basic genetic informationa HAR sequence, known evolutionary patterns, other functional genomics dataand returns a prediction of that HAR's function," explained Tony Capra, PhD, the study's lead author. "Using this approach, we predicted that nearly eight hundred HARs act as enhancers at a specific point during embryonic development. Confirming this prediction for several dozen HARs, our next goal was to see whether any of these HARs enhanced patterns of gene activation that were uniquely human."

Additional analyses revealed five such HARs, which were active in both human and chimpanzee genomes, but which activated genes in different embryonic regions. For example, the human versions of HARs 2xHAR.164 and 2xHAR.170 are active in a region of the brain between the midbrain and hindbrain, while the chimp versions are not. This so-called "gain of function" of these two HARs in human embryos may point to differences in the development of key brain regions such as the cerebellum, which is known to regulate not only motor control but may also regulate higher cognitive functions, such as language, fear and pleasure.

"These results, while preliminary, offer an unprecedented glimpse into how very recent changes to the human genome have modified the genetic programs that control embryonic development to potentially yield different results," said Dr. Capra. "We anticipate that if we were to look at the activity of HARs that are enhancers during later developmental stages, we would see even more differences between humans and chimpanzees."

"It's been 10 years since the Human Genome Project was declared 'complete,' but the amount of genomic knowledge we've gleaned since thenin large part due to advances in bioi
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Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
Source:Eurekalert  

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