Modern day reproductive systems are the result of changes in two letters of genetic code that took place 500 million years ago, a team of geneticists has discovered.
"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," Joe Thornton, a professor of human genetics, ecology and evolution at the University of Chicago, said in a statement.
Tweaks in how proteins function have been key to how humans evolve, and this study demonstrates how the smallest of mutations can be responsible for vital permanent changes. It also gives some insight as to how genetic code works to change those functions, and Thornton believes discoveries such as these will have a key role to play in developing targeted drugs that combat genetic mutations -- the better we understand how genetic mutations occur, the better equipped we'll be to combat unhelpful ones.
The team made the discovery by retracing today's steroid hormone receptor proteins' historical steps, choosing this group of proteins for their wide-ranging roles in controlling hormones for reproduction and development.
Working backward to the common link connecting all these proteins, a protein that only recognised oestrogen, the team looked for differences that caused it to morph into a family of proteins that recognise testosterone, progesterone and the stress hormone cortisol. They built a computational model of those ancestral relationships, inputting the genetic code of the hundreds of sequences that make up the modern receptors and then biochemically synthesised the ancestral sequences that emerged. Once these were engineered, the team could test to see what hormones the proteins would interact with.
After discovering roughly when steroids began to shoot off and create relations that could recognise other hormones (a mere 500 million years ago), they then introduced the different mutations identified into the engineered proteins. How their structure and functions were affected by these mutations was noted, and it was found that just two mutations at the atomic level resulted in the correct sequence, a sequence that changed the course of human reproduction, development, immunity and even our risk of cancer.
"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 Thornton.
That one shift has resulted in a 70,000-fold change in the protein. Although only two amino acids were affected, it meant oestrogen sensitivity was reduced markedly as the protein began to spread its attention across a variety of hormones.