For the current study, the researchers identified protein sequences in the genomes that had the same folding structure as known proteins. They then used bioinformatics techniques to compare them to each other on a time scale to determine when proteins became part of a particular organism. This allowed them to map protein structures and organisms onto a timeline.
Directly calculating the folding speed for all of these proteins would be impossible with today's technology, so the researchers took advantage of the fact that a protein always folds at the same points and used a measure called Size Modified Contact Order (SMCO).
Contact order is the ability of a protein to establish links between segments of the polypeptide chain. When points that are close together on the chain come together, they generally form helical structures; when distant points come together, they form beta strands that interact with each other and form sheets. Contact order measures how many of the connections are local and how many are distant. Experimental studies have shown that it is correlated with folding speed. The measure is normalized (size modified) to take protein length, which affects folding speed, into account.
They saw a peculiar pattern in the results.
"What we see is an hourglass," said Caetano-Anolls. "At the beginning, proteins seem not to be folding so fast. And then, as time progresses, there's a tendency to fold faster and faster. And then it reaches a critical point, and at this point we have a tendency that reverses, that seems to go back again to slow folding." However, the tendency toward higher speed dominates.
This point coincides with what he calls the "Big Bang" in protein evolution. Approximately 1.5 billion years ago, more complex domain structures and multi-domain proteins emerged with the appearance of multicellular organisms. Amino acid chains, which make
|Contact: Susan Jongeneel|
University of Illinois College of Agricultural, Consumer and Environmental Sciences