Two Mutations Triggered 'Hormonal Evolution' About 500 Million Years Ago

Just two mutations led to the formation of hormones about 500 million years back, according to a new study. Without this evolutionary jump, we would have to take different routes to reproduce and manage stress, researcher claim.

Experts call the study a kind of "molecular time travel," wherein they recreated the environment that existed millions of years back to see how genes began coding for certain hormones such as estrogen, testosterone and cortisol. These hormones regulate reproduction and stress in humans.

"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, lead author of the study, according to a

"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 in a news release.

According to the study, learning how genetic codes determine the function of a protein could lead to better understanding of a drug's effect on the body.

The study team also included researchers from the University of Oregon, Emory University and the Scripps Research Institute. Researchers started their work by studying the evolution of a kind of receptor in the body called steroid hormone receptors. These receptors are a class of proteins fused with hormones that regulate reproduction and physiology. The hormones couldn't affect the cells without the presence of these receptors.

Earlier, the entire receptor family just recognized estrogen. However, subsequent generations of the receptors learnt to recognize other steroid hormones such as testosterone, progesterone and cortisol.

Researchers resurrected ancient proteins using computer models and a database of hundreds of present-day receptor sequences. They event reconstructed ancient DNA sequences and looked at the hormonal sensitivity of ancient steroid receptors. The setting was made keeping in mind the mutations that took place 500 million years ago, before the vertebrates evolved.

The scientists observed the mutations that occurred in the setting. The steroid-receptors were recognizing just one hormone.

Researchers found that just two mutations at this point led to a drastic change in the receptors' sensitivity toward hormones. They went from preferring estrogen to accepting other steroid hormones.

The team further observed the exact atoms that changed the course of history. They found that changes in position of few atoms significantly changed the way the receptor interacted with the steroid hormones, leading to a change in the function of the protein.

Thornton added that these molecular changes and other undiscovered mutations led to the development of hormone signalling in the body.

The study is published in the journal Proceedings of the National Academy of Sciences.