Key Mutations Sparked Evolution Leap 500 Million Years Ago

Evolution doesn't always just crawl along, changing slowly over hundreds and thousands of generations. Sometimes it jumps. Scientists have discovered two key mutations that sparked a hormonal revolution about 500 million years ago.

In order to study the process of evolution, the researchers essentially wound back time in order to resurrect and analyze the functions of the ancestors of genes that play key roles in modern human reproduction, development, immunity and cancer. Yet actually accomplishing this feat wasn't easy. The scientists studied the evolution of a family of proteins called steroid hormone receptors, which mediate the effects of hormones that affect the body's cells.

In order to examine these hormone receptors, the scientists 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 DNA sequences and used molecular assays to determine the receptors' sensitivity to various hormones.

The scientists then narrowed down the time range during which the ability to recognize non-estrogen steroids evolved. They found that it occurred about 500 million years ago, a time before vertebrate animals appeared on Earth. They then identified the most important mutations and measured how they affected the receptor's structure and function. In the end, they found two changes that made a massive impact on our future.

"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, the lead researcher, in a news release. "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."

The findings are important for understanding how the genetic code of a protein determines its functions. This, in turn, can help biochemists better design drugs and predict the effects of mutations on disease. It also shows how the process of evolution can move in leaps due to tiny changes in the genetic code rather than just inching forward.

The findings are published in the journal Proceedings of the National Academy of Sciences.