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The study follows the evolutionary history of metabolic networks


IMAGE: University of Illinois professor Gustavo Caetano-Anolles and graduate student Fizza Mughal (pictured) used a bioinformatic approach to reconstruct the evolutionary history of metabolic networks.
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Credit: Illustration by Fred Zwicky Photograph

CHAMPAIGN, Ill. By analyzing how metabolic enzymes are produced and regulated, researchers have reconstructed the evolutionary history of metabolism. Researchers show how metabolic networks that drive every cellular process from protein formation to DNA repair become less random, more modular, and more hierarchical.

Studies published in journals PLOS ONEResearchers have reported that these studies shed light on the patchwork process that allows cells to shape metabolic pathways.

Eniz If you choose a network in the field of biology, it is the most important, önemli said Gustavo Caetano-Anollés, professor of crop science at the University of Illinois. “This network is responsible for negotiating not only matter but also energy (the two most essential elements for the work of an organism). Et Caetano-Anollés, a bioinformatics specialist and Carl R. Woese Institute of Genomic Biology in Illinois; is a member of.

To understand how cells build up their metabolic networks, researchers have focused on the enzymatic machines that lie at the heart of these networks. Enzymes promote specific chemical reactions to help create proteins, DNA, RNA, pigments, vitamins, fats, sugars, and other molecules necessary for life. They also support energy production in cells.

Scientists have analyzed the basic physical and functional components that contribute to how enzymes work. These components, called "folds," give proteins physical properties that enable them to work. Folds are like belts, pistons, gears and other mechanical parts that can be used repeatedly to make machines with very different functions.

"Folds represent the molecular innovations that cells repeatedly use in different contexts," Mughal said. Bak By looking at the folds across the tree of life, we were able to reconstruct the history of the folding families to show how closely or remotely the individual folds are related. this appeared more recently. "

Mughal used this information to color-code enzymes from known metabolic networks, depending on their age. When he linked color-coded enzymes to his own networks to form a metabolic database known as MANET, he found that each network was driven by a patch study of enzymes of different ages.

"This tells us that these networks have changed over time," Babur said. Said. Belirli Certain enzymes were collected in the cell to do new things, and old enzymes sometimes fell and disappeared. ”

When researchers examined how metabolic pathways evolved, they found that early metabolic networks were more random – and probably less efficient than today's networks, which gave a more modular and hierarchical configuration. Enzyme assemblages emerged and divided into paths, subnets and subnet groups.

Caetano-Anollés said that this modular hierarchy is a feature of other advanced networks, such as the Internet or the brain's neural networks.

In metabolism, the modularity and hierarchical nature of the network is most common at the enzyme level, he said.

"When you look at a higher level of network organization, the structure becomes more random." Said. "The connections are weaker. This makes the network as a whole more flexible."

“In this study, we tracked the history of metabolism step by step,” he said. Olan The gradual addition of more and more useful things to the cell. It gives us an idea of ​​how life machines become complicated. ”

Babur, "biological systems should be studied holistically because they reflect how nature works," he said. "No biological agent, from macromolecules to cells, organisms, is effective in isolation."


The US Department of Agriculture's National Food and Agriculture Institute and I. National Center for Supercomputing Applications in the US supported this research.

Editor's notes:

To contact Gustavo Caetano-Anollés, e-mail

To reach Fizza Mughal, send an email to

The article "MANET 3.0: Hierarchy and modularity in changing metabolic networks" is available online and from the I. News Bureau.

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