(Press-News.org) 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 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.
INFORMATION:
This work was supported by grants from the National Institutes of Health, National Science Foundation and the Howard Hughes Medical Institute.
END
EAST BOOTHBAY, MAINE -- A research team led by Bigelow Laboratory for Ocean Sciences has discovered that marine microbes are adapted to very narrow and specialized niches in their environment. This may explain why so few of these microbes—usually less than 1%—can be grown for study in the laboratory. By utilizing new genetic tools, the researchers' new ability to read and interpret genetic information from the remaining 99% will be pivotal in detecting and mitigating the impact of human activities in the ocean. Funded by the National Science Foundation, the study was published ...
COLUMBUS, Ohio – Some open-minded people can be swayed to support government intervention on climate change – but only if they are presented with both the benefits and the costs, a new study suggests.
Researchers found that those who were open-minded didn't change their view if they heard arguments for only one side of the issue.
People who are relatively more closed-minded did not change their mind regardless of the messages they received, or what their original views were. There was also no evidence of open-minded people becoming less supportive of government intervention, ...
Bacterial DNA may integrate into the human genome more readily in tumors than in normal human tissue, scientists have found.
The researchers, affiliated with the University of Maryland School of Medicine's Institute for Genome Sciences, analyzed genomic sequencing data available from the Human Genome Project, the 1,000 Genomes Project and The Cancer Genome Atlas.
They considered the phenomenon of lateral gene transfer (LGT), the transmission of genetic material between organisms in a manner other than than traditional reproduction.
Scientists have already shown ...
ROCHESTER, Minn. -- Rural women with breast cancer are less likely than their urban counterparts to receive recommended radiation therapy after having a lumpectomy, a breast-sparing surgery that removes only tumors and surrounding tissue, a study by Mayo Clinic and others found. The difference is one of several rural disparities in breast cancer diagnosis and treatment the researchers discovered. The findings are being presented at the AcademyHealth Annual Research Meeting in Baltimore.
"These study results are concerning," says Elizabeth Habermann, Ph.D., associate scientific ...
Several studies have shown that how much parents say to their children when they are very young is a good predictor of children's vocabulary at the point when they begin school. In turn, a child's vocabulary size at school entry strongly predicts level of success throughout schooling even into high school and college.
A new study by psychologists at the University of Pennsylvania now shows that early vocabulary improvement is likely to have more to do with the "quality" of the interactions in which the words are used rather than the sheer quantity of speech directed ...
Just what size is a "small" drink—8 ounces, 12 ounces, 16 ounces? The truth is, those are all "small" sizes depending on what restaurants and fast food joints you go to. As customers, we are used to ordering food based on relative size, but according to a new study from Cornell University, these seemingly standard labels impact our entire eating experience.
Dr. David R. Just and Dr. Brian Wansink of the Cornell Food & Brand Lab designed a study to understand how portion labels impact what you're willing to pay for your food as well as how much you actually eat. The researchers ...
A new study by researchers at the Ernest Gallo Clinic and Research Center at UC San Francisco offers encouraging findings that researchers hope may one day lead to a treatment option for people who suffer from alcohol abuse disorders and other addictions.
In the study, conducted in rats, the UCSF researchers were able to identify and deactivate a brain pathway linked to the memories that cause cravings for alcohol, thus preventing the animals from seeking alcohol and drinking it, the equivalent of relapse.
"One of the main causes of relapse is craving, triggered by ...
PITTSBURGH—A landmark study investigating the long-term effects of weight loss on the risks of cardiovascular disease among patients with Type 2 diabetes has now concluded, with significant results to be published today in the New England Journal of Medicine.
Conducted at the University of Pittsburgh and at clinical facilities throughout the United States, the multicenter clinical trial investigated the effects of an intensive lifestyle intervention program, intended to achieve and maintain weight loss in overweight or obese people with Type 2 diabetes, on rates of cardiovascular ...
OAK BROOK, Ill. – Despite concerns to the contrary, very little of the variation in Emergency Department (ED) imaging utilization is attributable to physician experience, training or gender, according to a new study published online in the journal Radiology.
Imaging exams like X-rays and CT scans are common in the ED. In 2010, slightly more than 47 percent of all ED visits in the United States had an imaging exam associated with them.
"Analyzing and understanding drivers of use of imaging in the ED is important for several reasons," said Christopher L. Sistrom, M.D., ...
OAK BROOK, Ill. – Moderate-intensity exercise reduces fat stored around the heart, in the liver and in the abdomen of people with type 2 diabetes mellitus, even in the absence of any changes in diet, according to a new study published online in the journal Radiology.
Type 2 diabetes occurs when the body does not produce enough insulin, a hormone that regulates the movement of sugar into the cells, or when the cells resist the effects of insulin. The disease can lead to a wide range of complications, including damage to the eyes and kidneys and hardening of the arteries.
Exercise ...
