Two mutations triggered an evolutionary leap 500 million years ago

Two mutations triggered an evolutionary leap 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 family -- which recognized only estrogens -- evolved 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.

Welcome to SUV System Ltd!

SUV System Ltd is ISO 90012008 Certified electronics distributor with 10 years of experiences.

We have built up long term business relationship with about many companies which are stockers and authorized agents. we have a steady and reliable supply to meet customer's demands to the greatest extent .Confidently, we are able to lower your cost and support your business with our years of professional service.

SUV System Ltd is Electronic Components Distributor Supplies,Find Quality Electronic Components Supplies Products IC(Integrated Circuits),Connectors,Capacitor,Resistors,Diodes,Transistors,LED at Suvsystem.com. Sourcing Other Energy, Environment, Excess Inventory Products from Manufacturers and Suppliers at Suvsystem.com

Electronic Components distributor:http://www.suvsystem.com

Connectors Distributor:http://www.suvsystem.com/l/Connectors-1.html

IC Distributor:http://www.suvsystem.com/l/IC(Integrated-Circuits)-1.html

LED Distributor:http://www.suvsystem.com/l/LED-1.html

Capacitor Distributor:http://www.suvsystem.com/l/Capacitor-1.html

Transistor Distributor:http://www.suvsystem.com/l/Transistors-1.html

Resistor Distributor:http://www.suvsystem.com/l/Resistors-1.html

Diode Distributor:http://www.suvsystem.com/l/Diodes-1.html

SUV System Ltd insists on the managing faith ofsincereness,speciality,foresight, win-win,so we build up stable-relationship customers located all over the world, including the States, Europe, Argentina, UAE, Malaysia, Australia,and India etc

we are focus on the following fields,and hope we can help you.

B41252A8828M000 B41252A8828M B41252A8688M000 B41252A8688M B41252A8568M000 B41252A8568M B41252A8478M000 B41252A8478M B41252A8398M000 B41252A8398M B41252A8338M000 B41252A8338M B41252B4339M000 B41252B4279M000 B41252B4279M B41252B4229M000 B41252B4229M B41252B4189M000 B41252B4159M000 B41252B4159M B41252B4129M000 B41252B4129M B41252B4109M000 B41252B4109M B41252B398M B41252B3479M000 B41252B3479M B41252B3399M000 B41252B3399M B41252B338M B41252B3339M000 B41252B3339M B41252B3279M000 B41252B3229M000 B41252B3229M B41252B3189M000 B41252B3189M B41252B3159M000 B41252B3159M B41252B278M
http://www.suvsystem.com/a/3186.aspx