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

Structure of 450 Million Year Old Protein Reveals Evolution’s Steps

Published: Wednesday, August 22, 2007
Last Updated: Wednesday, August 29, 2007
Bookmark and Share
Researchers have determined the atomic structure of an ancient protein, revealing in detail how genes evolved their functions.

A detailed map that pinpoints the location of every atom in a 450-million-year-old resurrected protein reveals the precise evolutionary steps needed to create the molecule’s modern version, according to researchers from the University of North Carolina at Chapel Hill and the University of Oregon.

Until now, scientists trying to unravel the evolution of the proteins and other molecules necessary for life have worked backwards, making educated guesses based on modern human body chemistry. By moving forward from an ancient protein, the team laid out the step-by-step progression required to reach its current form and function.

The study appeared online Aug. 16, 2007, in ScienceXpress.

“We were able to see exactly how mutations in the ancient structure led to the modern receptor,” said lead author Eric Ortlund, who carried out the research as a UNC-Chapel Hill postdoctoral fellow. Ortlund is now an assistant professor of biochemistry in the Emory University School of Medicine.

In the current study, Ortlund and Matt Redinbo, a professor of chemistry, biochemistry and biophysics at UNC-Chapel Hill, generated a three-dimensional picture of the ancient receptor with an imaging technique called X-ray crystallography. The nanoscale image revealed the receptor’s structure, down to the placement of every atom. With the structure in place, Ortlund and his colleagues retraced evolution’s path.

The researchers examined the precursor to a modern protein known as a glucocorticoid receptor. In humans, the receptor plays a crucial role, responding to the hormone cortisol and regulating the body’s stress response. The two – receptor and hormone – fit together as precisely as a lock and key. The precursor preferred a different hormone, so several mutations were necessary before the lock could fit the cortisol key.

The University of Oregon team, which included postdoctoral scientist Jamie Bridgham, resurrected the ancient protein via a large database of modern receptor genes. This earlier work, which compared the genetic similarities and differences among two of these modern genes, found the receptor descended from a single common genetic ancestor 450 million years ago. The researchers then recreated the ancient receptor in the laboratory.

Only seven mutations were needed to bridge the 450-million-year gulf, the researchers found. However, not every mutation changed the protein’s function. These permissive mutations appear to pave the way for future, more significant changes. “It’s like they prepared for opportunity to knock in the form of a new hormone,” Ortlund said.

The permissive mutations bolstered the receptor’s structure, like contractors reinforce a historic home’s foundation before making renovations. After these changes took place, a more extreme mutation repositioned an entire group of atoms, bringing them closer to fitting the cortisol hormone. Another created the tight new fit with cortisol.

“These permissive mutations are chance events. If they hadn’t happened first, then the path to the new function could have become an evolutionary road not taken,” said co-author Joe Thornton, a professor of evolutionary biology at the University of Oregon.

The researchers worked out which mutations came first by synthesizing different versions of the mutated protein in the laboratory. Had the radical mutations come first, the receptor protein would have lost its function entirely, they found.

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

Autism Mutation Isolated – Could Be Treated with Specific Enzyme
The research shows the precise cellular mechanisms that could increase risk for the disorder and how an existing drug might help thousands of people with autism.
Monday, August 10, 2015
New Gene Therapy For Hemophilia Shows Potential As Safe Treatment
Research showed that bleeding events were drastically decreased in animals with hemophilia B. Using a viral vector to swap out faulty genes proved safe and could be used for the more common hemophilia A.
Tuesday, March 17, 2015
Genetically Speaking, Mammals Are More Like Their Fathers
A first of its kind study shows that who we inherit genetic variants from – our mother or father – is crucial for the development of diseases and for research studies aimed at finding causes and potential treatments.
Wednesday, March 04, 2015
Researchers Silence Leading Cancer-Causing Gene
A novel siRNA-based molecule successfully targets KRAS, a well-studied but hard to halt protein important for cancer development and metastasis.
Monday, November 17, 2014
New Gene Therapy Proves Promising as Hemophilia Treatment
Researchers package specialized blood platelets with genes that express clotting factor, leading to fewer bleeding events.
Wednesday, December 18, 2013
New Findings Regarding DNA Damage Checkpoint Mechanism in Oxidative Stress
Scientists uncover previously unknown surveillance mechanism.
Thursday, June 20, 2013
Molecular Twist Helps Regulate the Cellular Message to Make Histone Proteins
Researchers show for the first time how two key proteins in messenger RNA communicate via a molecular twist to help maintain the balance of histones to DNA.
Monday, January 21, 2013
Informatics Approach Helps Doctors, Patients Make Sense of Genome Data
Researchers from UNC unveil an analysis framework aimed at helping clinicians spot “medically actionable findings” from genetic tests in an efficient manner.
Friday, September 21, 2012
Molecular Delivery Truck Serves Gene Therapy Cocktail
University of North Carolina scientists have devised a gene therapy cocktail that has the potential to treat some inherited diseases associated with “misfolded” proteins.
Tuesday, August 23, 2011
Clinical Trial of Molecular Therapy for Muscular Dystrophy Yields Significant Positive Results
A molecular technique originally developed at the University of North Carolina at Chapel Hill has taken one step closer to becoming a treatment for the devastating genetic disease Duchenne muscular dystrophy.
Tuesday, July 26, 2011
Gene Discovered by Researchers Tied to Pancreatic Cancer
The gene, palladin, is involved is involved in the formation of scar tissue on nerve cells in the brain or spinal cord.
Monday, December 18, 2006
Three Lung Tumor Subtypes Identified in DNA Profiling Study
The finding may provide clinical information about patient survival in early- or late-stage disease.
Thursday, November 02, 2006
Studies Find General Mechanism of Cellular Aging
Studies suggest tumor suppressor gene is key.
Friday, September 08, 2006
Novel Enzyme Offers new Look at Gene Regulation
Scientists show that a protein called JHDM1A is able to remove a methyl group from histone H3.
Wednesday, December 28, 2005
Scientific News
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Tardigrade's Are DNA Master Thieves
Tardigrades, nearly microscopic animals that can survive the harshest of environments, including outer space, hold the record for the animal that has the most foreign DNA.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
GMO Food Animals Should be Judged by Product, Not Process
In a world with a burgeoning demand for meat, milk and eggs, regulatory policies around the use of biotechnologies in agriculture need to be based on the safety and attributes of those foods rather than on the methods used to produce them, says a UC Davis animal scientist.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
Gene Drive Reversibility Introduces New Layer of Biosafety
Ability to introduce or reverse the spread of genetic traits through populations could one day improve pest management and disease control.
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.
University of Glasgow Researchers Make An Impact in 60 Seconds
Early-career researchers were invited to submit an engaging, dynamic and compelling 60 second video illuminating an aspect of their research.
Skyscraper Banner

Skyscraper Banner
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