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ScienceDaily_2013 15536.txt

#Untangling lifes originsresearchers in the Evolutionary Bioinformatics Laboratory at the University of Illinois in collaboration with German scientists have been using bioinformatics techniques to probe the world of proteins for answers to questions about the origins of life. Proteins are formed from chains of amino acids and fold into three-dimensional structures that determine their function. According to crop sciences professor Gustavo Caetano-Anoll s very little is known about the evolutionary drivers for this folding. In collaboration with scientists at the Heidelberg Institute for Theoretical Studies he has been working at the interface of molecular evolution and molecular dynamics looking back to when proteins first appeared approximately 3. 8 billion years ago to determine changes in folding speed over time. To do this they looked at all known protein structures as defined in the Structural Classification of Proteins (SCOP) database and mined their presence in 989 fully sequenced genomes. In a previous study researchers in Caetano-Anoll s's group used SCOP and genomic information to reconstruct phylogenomic trees that describe the history of the protein world. The current research is based on these types of trees. They are not the standard trees that people see in phylogenetic analysis he said. In phylogenetic analysis usually the tips of the trees the leaves are organisms or microbes. In these they are entire biological systems. In contrast the leaves of these new trees are protein domains which are compact evolutionary units of structure and function. Proteins are usually complex combinations of several domains. We have a world of about 90000 of these structures but they seem to be always producing the same designs he said. Over the last 10 years he has been part of the effort to map these designs or folds because they are determined by the way the protein chains fold on themselves. To date approximately 1300 folds have been characterized. 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 said an hourglass Caetano-Anoll s. 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 up proteins also became shorter at this point in time. Why does speed folding matter? If the protein does not fold in the vast majority of cases it will not have a function. So folding implies functionality. And speed of folding implies speed of achieving that functionality he explained. For a cell that's very important because if proteins are very slow folders there is a time lag to when that function will be accessible to the cell. Fast folders are also less susceptible to aggregation or clumping together so they work faster. Moreover proteins that fold rapidly are more likely to fold correctly. Protein misfolding has been linked with diseases such as Alzheimer's. Caetano-Anoll s said however that this research makes an important contribution to understanding how molecules work. The complexities of the biological functions of molecules are understood still poorly he said. If we mix the world of molecular dynamics with the world of molecular evolution we can then determine what aspects of sequences are important for molecular dynamics and therefore we can apply them to genetic engineering synthetic biology and so on. Story Source: The above story is provided based on materials by University of Illinois College of Agricultural Consumer and Environmental sciences. Note: Materials may be edited for content and length. Journal Reference e

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