Rice University researchers, led by Peter Wolynes, have made a significant breakthrough in understanding how specific genetic sequences known as pseudogenes evolve. Pseudogenes are segments of DNA that once coded for proteins but have lost their ability to do so due to sequence degradation, a process known as devolution. The team’s research focused on decoding the complex energy landscapes of de-evolved pseudogenes to gain insights into how proteins can de-evolve without the usual evolutionary pressures that regulate functional protein-coding sequences.
Their study revealed that mutations in pseudogene sequences disrupt the native network of stabilizing interactions, making it difficult for these sequences to fold into functional proteins if they were to be translated. However, the researchers also observed instances where specific mutations unexpectedly stabilized the folding of pseudogenes at the expense of altering their original biological functions. This indicates a delicate balance between protein stability and biological activity within pseudogenes and highlights the dynamic nature of protein evolution.
The research team identified specific pseudogenes, such as cyclophilin A, profilin-1, and small ubiquitin-like modifier 2 protein, where stabilizing mutations occurred in regions crucial for binding to other molecules and other functions. These findings suggest that proteins can de-evolve over time due to mutations or other factors, and some previously pseudogenized genes may regain their protein-coding function despite undergoing multiple mutations. The study also emphasizes the interplay between physical folding landscapes and evolutionary landscapes of pseudogenes, providing evidence that evolution shapes the folding of proteins.
By using sophisticated computational models, the researchers were able to interpret the relationship between protein folding landscapes and the evolution of pseudogenes. Their results offer direct evidence that proteins can de-evolve, compromising their ability to fold due to mutations or other factors. This research has implications beyond theoretical biology and could have potential applications in protein engineering. The team hopes that their findings can be confirmed through experimental validation to further understand what happens to pseudogenes that are more physically stable and how they may evolve over time.
Overall, Rice University’s research on pseudogene evolution sheds light on the complex process of how proteins de-evolve and lose their ability to fold over time. By studying the energy landscapes of de-evolved pseudogenes, the researchers have provided insights into the dynamic nature of protein evolution and the delicate balance between protein stability and biological activity. This research has the potential to impact various fields, including protein engineering, and further studies could confirm and expand upon these findings to deepen our understanding of evolutionary processes in proteins.