So what does all this have to do with managing the disruption of mutations? Our research looks at the repetitive elements that were copied within the genome of the ancestors of modern primates. There are over 1.6m of these “Alu elements” dispersed all over the human genome, and some of them have accumulated random mutations that enabled them to become functional parts of our genes.
We have found a code in the RNA that controls Alu elements hiding inside human genes. This code combines competing positive and negative molecular forces, like a ying and yang in our cells. It is well known that competing molecular forces control many aspects of our genes. In our case, the positive force (acting through the protein called U2AF65) allows the Alu elements to remain part of RNA and the resulting protein. The negative force (acting through the protein called hnRNPC) opposes this and removes the elements from the RNA.
We’ve known for decades that evolution needs to tinker with genetic elements so they can accumulate mutations while minimising disruption to the fitness of a species. Our most recent research, published in the journal eLife, looked at over 6,000 Alu elements to show that our code does exactly this.
The two forces are tightly coupled in evolution, so that as soon as any mutations make the ying stronger, the yang catches up and stops them. This allows the Alu elements to remain in a harmless state in our DNA over long evolutionary periods, during which they accumulate a lot of change via mutations. As a result, they become less harmful and gradually start escaping the repressive force. Eventually, some of them take on an important function and became indispensable pieces of human genes.
To put it another way, the balanced forces buy the time needed for mutations to make beneficial changes, rather than disruptive ones, to a species. And this is why evolution proceeds in such small steps – it only works if the two forces remain balanced by complementary mutations, which takes time. Eventually, important new molecular functions can emerge from randomness.
These findings tell us that humans are not a fixed pinnacle of evolution. Our genomes are like those of any other species: a fluid landscape of DNA sequences that keep changing. This explains how our genome can host its ever-changing repetitive elements despite their potential to disrupt the existing order in our cells.