Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Fast-Mutating DNA Sequences Shape Early Development

Published: Wednesday, November 13, 2013
Last Updated: Wednesday, November 13, 2013
Bookmark and Share
What does it mean to be human? According to scientists the key lies, ultimately, in the billions of lines of genetic code that comprise the human genome.

The problem, however, has been deciphering that code. But now, researchers at the Gladstone Institutes have discovered how the activation of specific stretches of DNA control the development of uniquely human characteristics – and tell an intriguing story about the evolution of our species.

In the latest issue of Philosophical Transactions of the Royal Society B, researchers in the laboratory of Gladstone investigator Katherine Pollard, PhD, use the latest sequencing and bioinformatics tools to find genomic regions that guide the development of human-specific characteristics. These results offer new clues as to how the activation of similar stretches of DNA – shared between two species – can sometimes result in vastly different outcomes.

“Advances in DNA sequencing and supercomputing have given us the power to understand evolution at a level of detail that just a few years ago would have been impossible,” said Pollard, who is also a professor of epidemiology and biostatistics at UC San Francisco's Institute for Human Genetics. Gladstone is affiliated with UCSF.

“In this study, we found stretches of DNA that evolved much more quickly than others," she said. "We believe that these fast-evolving stretches were crucial to our human ancestors becoming distinct from our closest primate relatives.”

These stretches are called human accelerated regions, or HARs, so-called because they mutate at a relatively fast rate. In addition, the majority of HARs don’t appear to encode specific genes. The research team hypothesized that HARs instead acted as “enhancers,” controlling when and for how long certain genes were switched on during embryonic development.

Through experiments in embryonic animal models, combined with powerful computational genomics analyses, 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 information – a HAR sequence, known evolutionary patterns, other functional genomics data – and returns a prediction of that HAR’s function,” explained Tony Capra, PhD, the study’s lead author.

“Using this approach, we predicted that nearly 800 HARs act as enhancers at a specific point during embryonic development," he said. "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 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 then – in large part due to advances in bioinformatics and supercomputing – have catapulted us far beyond what we thought we knew,” added Pollard. “I’m confident that as we continue to dive deep into important regions such as HARs, we’ll come ever closer to answering the question: what makes us human?’”

Capra completed this research during a postdoctoral fellowship Gladstone and is now an assistant professor at Vanderbilt University. UCSF graduate student Genevieve Erwin also participated in this research at Gladstone, which was supported by grants from the National Institute of General Medical Sciences (#GM082901) and the National Heart, Lung and Blood Institute (#HL098179), A PhRMA Foundation Fellowship, a University of California Achievement Awards for College Scientists (ARCS) Scholarship and a gift from the Sam Simeon Fund.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
Monday, November 23, 2015
Clearest Ever Images of Enzyme that Plays Key Roles in Aging, Cancer
UCLA-led research on telomerase could lead to new strategies for treating disease
Monday, October 19, 2015
Crop Cure
Scientists in new center to use medical research techniques to help food crops withstand drought and climate change.
Friday, October 16, 2015
Rare Childhood Leukemia Reveals Surprising Genetic Secrets
A coalition of leukemia researchers led by scientists from UC San Francisco has discovered surprising genetic diversity in juvenile myelomonocytic leukemia (JMML), a rare but aggressive childhood blood cancer.
Thursday, October 15, 2015
Double Enzyme Hit May Explain Common Cancer Drug Side Effect
Mouse study suggests genomic screening before treatment may help prevent anemia.
Wednesday, October 14, 2015
New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
Wednesday, September 30, 2015
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Simple Technology Makes CRISPR Gene Editing Cheaper
University of California, Berkeley, researchers have discovered a much cheaper and easier way to target a hot new gene editing tool, CRISPR-Cas9, to cut or label DNA.
Friday, July 24, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 2015
Industry-Sponsored Academic Inventions Spur Increased Innovation
Analysis questions assumption that corporate support skews science toward inventions that are less useful than those funded by the government or non-profit organizations.
Monday, March 24, 2014
Researchers Change Cell Types by Flipping a Single Switch
New findings have identified a method for changing one cell type into another in a process called forced transdifferentiation.
Friday, December 06, 2013
Scientists Pinpoint Cell Type and Brain Region Affected by Gene Mutations in Autism
UCSF-led study zeroes in on when and where disrupted genes exert effects.
Tuesday, November 26, 2013
Digging Deeper Into Cancer
What a pathologist looks for in a Pap test sample, but hopes not to find, are oddly shaped cells with abnormally large nuclei. The same is true for prostate and lung cancer biopsies.
Tuesday, November 19, 2013
Nanotech Method Show Promise Against Pancreatic Cancer
Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed a new technique for fighting deadly and hard-to-treat pancreatic cancer.
Monday, November 18, 2013
Scientific News
Revolutionary Technologies Developed to Improve Outcomes for Lung Cancer Patients
Breath test to detect lung cancer brings oxygen directly to the wound.
Dementia Linked to Deficient DNA Repair
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer’s disease.
New Gene Map Reveals Cancer’s Achilles’ Heel
Team of researchers switches off almost 18,000 genes
New Discovery Sheds Light on Disease Risk
Gaps between genes interact to influence the risk of acquiring disease.
Mathematical Model Helps Show How Zebrafish Get Their Stripes
The iconic yellow and blue stripes of zebrafish form dynamically as young fish develop and grow. A mathematical model developed by Brown University researchers helps to show how pigment cells interact to form the pattern.
Epigenome Influenced by Habitat and Lifestyle
Study on Pygmy hunter-gatherer populations and Bantu farmers in Central Africa shows that habitat and lifestyle can impact the epigenome.
Shining Light on Microbial Growth and Death Inside our Guts
Precise measurement of microbial populations in gastrointestinal tracts could be key to identifying novel therapies.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos