A new study led by Peter Wolynes of Rice University provides new insights into the evolution of folding proteins. The research has been published in the Proceedings of the National Academy of Sciences.
Researchers from Rice and the University of Buenos Aires used energy landscape theory to distinguish between folding and non-folding parts of protein sequences. Their research sheds light on the ongoing debate over whether the stretches of DNA that code for only part of a protein during their creation can fold independently.
The researchers focused on the extensive relationship between exons in protein structures and the evolution of protein foldability. They emphasized the importance of exons, the parts of the gene that code for proteins, and introns, the silent regions that are discarded during gene translation into proteins.
“Using the extensive genomic exon-intron organization and protein sequence data now available, we investigated the conservation of the exon boundary and assessed its behavior using theoretical measurements of the energy landscape,” said Wolynes, professor of science at the DR Bullard-Welch Foundation, Professor of Chemistry, Life Sciences. , physics and astronomy and co-director of the Center for Theoretical Biological Physics (CTBP).
When genes were discovered in pieces in the 1970s, it was immediately proposed that this structure, by breaking up the sequence, helped build foldable proteins. When researchers looked at this again in the 1990s, the existing data was ambiguous, Wolynes said.
The team has now assessed exons as potential protein folding modules in 38 abundant and conserved protein families. Over generations, exons can shuffle randomly along the genome, leading to significant changes in genes and the creation of new proteins. The findings indicated deviations in exon size distribution from exponential decay, indicating evolutionary selection.
“Protein folding and evolution are closely linked phenomena,” says Ezequiel Galpern, a postdoctoral researcher at the University of Buenos Aires.
Natural proteins are linear chains of amino acids that typically fold into compact three-dimensional structures to perform biological functions. The specific sequence of amino acids dictates the final 3D structure. Therefore, the idea that exons translate into independently folded protein regions, or foldons, is very attractive.
Using computational methods, the researchers measured the probability that the amino acid chain encoded by an exon would fold into a stable 3D structure, similar to the full protein. Their results showed that although not all exons led to folding modules, the most conserved exons, consistently found across organisms, corresponded to better foldons.
The study found a correlation between protein folding and evolution in certain globular protein families. Protein folding involves folding amino acid chains in space to perform biological functions within relevant timescales. This correlation is a fundamental concept in protein science, assessed through genomic data and energy functions.
Interestingly, the general trend did not apply to all protein families, suggesting that other biological factors may influence protein folding and evolution. The researchers’ work paves the way for future studies to understand these additional factors and their impact on evolutionary biology.
