Navigation Links
2 mutations triggered an evolutionary leap 500 million years ago

Evolution, it seems, sometimes jumps instead of crawls.

A research team led by a University of Chicago scientist has discovered two key mutations that sparked a hormonal revolution 500 million years ago.

In a feat of "molecular time travel," the researchers resurrected and analyzed the functions of the ancestors of genes that play key roles in modern human reproduction, development, immunity and cancer. By re-creating the same DNA changes that occurred during those genes' ancient history, the team showed that two mutations set the stage for hormones like estrogen, testosterone and cortisol to take on their crucial present-day roles.

"Changes in just two letters of the genetic code in our deep evolutionary past caused a massive shift in the function of one protein and set in motion the evolution of our present-day hormonal and reproductive systems," said Joe Thornton, PhD, professor of human genetics and ecology & evolution at the University of Chicago, who led the study.

"If those two mutations had not happened, our bodies today would have to use different mechanisms to regulate pregnancy, libido, the response to stress, kidney function, inflammation, and the development of male and female characteristics at puberty," Thornton said.

The findings were published online June 24 in the Proceedings of the National Academy of Sciences.

Understanding how the genetic code of a protein determines its functions would allow biochemists to better design drugs and predict the effects of mutations on disease. Thornton said the discovery shows how evolutionary analysis of proteins' histories can advance this goal, Before the group's work, it was not previously known how the various steroid receptors in modern species distinguish estrogens from other hormones.

The team, which included researchers from the University of Oregon, Emory University and the Scripps Research Institute, studied the evolution of a family of proteins called steroid hormone receptors, which mediate the effects of hormones on reproduction, development and physiology. Without receptor proteins, these hormones cannot affect the body's cells.

Thornton's group traced how the ancestor of the entire receptor familywhich recognized only estrogensevolved into descendant proteins capable of recognizing other steroid hormones, such as testosterone, progesterone and the stress hormone cortisol.

To do so, the group used a gene "resurrection" strategy. They first inferred the genetic sequences of ancient receptor proteins, using computational methods to work their way back up the tree of life from a database of hundreds of present-day receptor sequences. They then biochemically synthesized these ancient DNA sequences and used molecular assays to determine the receptors' sensitivity to various hormones.

Thornton's team narrowed down the time range during which the capacity to recognize non-estrogen steroids evolved, to a period about 500 million years ago, before the dawn of vertebrate animals on Earth. They then identified the most important mutations that occurred during that interval by introducing them into the reconstructed ancestral proteins. By measuring how the mutations affected the receptor's structure and function, the team could re-create ancient molecular evolution in the laboratory.

They found that just two changes in the ancient receptor's gene sequence caused a 70,000-fold shift in preference away from estrogens toward other steroid hormones. The researchers also used biophysical techniques to identify the precise atomic-level mechanisms by which the mutations affected the protein's functions. Although only a few atoms in the protein were changed, this radically rewired the network of interactions between the receptor and the hormone, leading to a massive change in function.

"Our findings show that new molecular functions can evolve by sudden large leaps due to a few tiny changes in the genetic code," Thornton said. He pointed out that, along with the two key changes in the receptor, additional mutations, the precise effects of which are not yet known, were necessary for the full effects of hormone signaling on the body to evolve.


Contact: Kevin Jiang
University of Chicago Medical Center

Related medicine news :

1. Rare genomic mutations found in 10 families with early-onset, familial Alzheimers disease
2. Mutations in susceptibility genes common in younger African American women with breast cancer
3. Mount Sinai Researchers Identify Gene Mutations in Congenital Heart Disease
4. Tumors with ALK rearrangements can harbor more mutations
5. Some patients with incurable tumors and BRCA mutations respond to new 2-drug combination
6. Blood tests can provide fuller picture of mutations in cancer than traditional biopsies do
7. Pathologists identify patterns of mutations to help inform design of future trials
8. Gene Mutations Appear Key to Childhood Leukemia Risk, Study Says
9. University of Minnesota researchers discover enzyme behind breast cancer mutations
10. Some cancer mutations slow tumor growth
11. Researchers discover mutations linked to relapse of childhood leukemia
Post Your Comments:
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... , ... “The Journey: From the Mountains to the Mission Field”: the story ... the Philippines. “The Journey: From the Mountains to the Mission Field” is the creation ... has taught all ages and currently teaches a class of ladies at her church, ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... ... Asante, a nationally recognized health system in southern Oregon, ... health joint venture through an agreement, effective October 1, 2017, to create AccentCare ... company with Asante, delivering clinically integrated care, for the past eight years. This ...
(Date:10/12/2017)... ... ... Leading pediatric oncology experts at Children’s National Health System will ... the International Society of Paediatric Oncology (SIOP) Oct. 12-15. Chaired by Jeffrey ... Disorders at Children’s National, and Stephen P. Hunger, M.D., Chief of the Division ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... Oct. 2, 2017 The Rebound mobile app is ... to reverse the tide of prescription drug addiction. The app ... medicine intake and stepping down their dosage in a safe, ... in December 2017; the first 100,000 people to sign up ... ...
(Date:9/27/2017)... , Sept. 27, 2017  DarioHealth Corp. (NASDAQ: DRIO), a leading ... announced that its MyDario product is expected to appear on The Dr. ... The Dr. Oz Show airs in your area: ... The nine-time Emmy award-winning, The Dr. Oz Show ... The segment ...
(Date:9/22/2017)... ROCKVILLE, Md. , Sept. 22, 2017  As ... by Republican Senators Bill Cassidy (R-LA) and ... Kalorama Information notes that the medical device industry is ... the medical device tax, the 2.3% excise tax on ... Act.  But they also want covered patients, increased visits ...
Breaking Medicine Technology: