ISB Scientists Discover How Microbes Adapt Quickly to New Environments

SEATTLE - Relocating is stressful, even for a microbe. Knowing how a microorganism can quickly adapt to challenges of a new habitat helps researchers better understand how commensals (good microbes) and pathogens colonize diverse environments including soil, plant roots, and the human gut. Institute for Systems Biology (ISB) researchers are the first to discover that a protein once thought to have no regulatory function in microbes actually helps them to rapidly adapt to new environments.

ISB scientists had previously discovered that the gene encoding this protein, called transcription factor B (TFB), is present in multiple copies in many microorganisms called archaea – especially those that are known to live in environments that are constantly changing. To understand why, the researchers used an interdisciplinary systems approach that systematically analyzed across many environments the consequences of deleting each copy of the gene or introducing a mutated copy on the health of one such organism, Halobacterium salinarum, that lives in saturate brine.

Simultaneously, they observed how all of the other genes and the complex molecular networks in H. salinarum responded to these genetic manipulations. They integrated millions of data points generated from thousands of such experiments and analyzed patterns in these data across evolutionary timescales by analyzing genome sequences of diverse organisms. They made the remarkable discovery that the microbe gained capability for acclimating to new environments by simply transferring genetic information from one copy of the TFB gene to another, akin to cutting and replacing text in one copy of a document from an edited version. Because it has seven variant copies of TFBs, H. salinarum could perform a large array of such mix-and-match experiments to explore new solutions for adaptation.

How does this work? Nitin Baliga, Professor and Director of ISB and senior author on the paper, explained that "TFBs bind to different locations in the genome and function like wires inside the cell to execute programs that determine which genes in the genome need to be turned on or off and when." In other words, by transferring information across TFBs, an organism can rapidly rewire its networks to generate new programs that enable new capabilities with the same set of genes.

"It´s astounding," remarked Dr. Baliga.

This discovery helps us to understand how archaea colonize diverse environments to give structure and function to microbial communities. This is important for two reasons: First, archaea make up 20 percent of biomass on earth and serve important roles in biogeochemical cycles, which are similar to our circulatory systems and necessary to maintain a health planet. Second, understanding the mechanics of adaptation will help us better understand and predict how microbes and communities might respond to pollution or climate change due to anthropogenic activities. Furthermore, because they have similar functions in eukaryotic organisms we can also begin to understand how duplicated copies of TFIIB proteins reorganize networks for development of body plans in animals.

Understanding that this family of proteins in archaea have regulatory consequences for adaptation into new environments is "knowledge that can be applied to understanding how the TFIIB proteins might have come to mediate the encoding and execution of regulatory programs in humans," said Serdar Turkarslan, the lead author of the paper, which was published on Nov. 22 in "Molecular Systems Biology."

This study was supported by the U.S. Department of Energy´s Genomic Science Funding, the National Institutes of Health, and the National Science Foundation.

About the Institute for Systems Biology
The Institute for Systems Biology (ISB) is an internationally renowned, non-profit research institute headquartered in Seattle and dedicated to the study and application of systems biology. Founded by Leroy Hood, Alan Aderem and Ruedi Aebersold, ISB seeks to unravel the mysteries of human biology and identify strategies for predicting and preventing diseases such as cancer, diabetes and AIDS. ISB's systems approach integrates biology, computation and technological development, enabling scientists to analyze all elements in a biological system rather than one gene or protein at a time. Founded in 2000, the Institute has grown to 13 faculty and more than 300 staff members; an annual budget of more than $50 million; and an extensive network of academic and industrial partners. For more information about ISB, visit www.systemsbiology.org