Evolution writ small: Study measures physical effects of evolution at molecular scale

Aug 25, 2010

A unique experiment at Rice University that forces bacteria into a head-to-head competition for evolutionary dominance has yielded new insights about the way Darwinian selection plays out at the molecular level. An exacting new analysis of the experiment has revealed precisely how specific genetic mutations impart a physical edge in the competition for survival.

The new research, which could lead to more effective strategies to combat resistance, was the most downloaded article this month in the journal Molecular Systems Biology.

The research builds upon an ingenious 2005 study involving bacteria called "thermophiles," which thrive at high temperatures. Researchers in the laboratory of Rice biochemist Yousif Shamoo "knocked out" a key gene that allowed the thermophiles to make energy at high temperatures. These crippled versions of the bacteria were then grown inside fermentors for several weeks. Each day, the temperature of the fermentors was increased. As a result, the bacteria were forced to either starve or adapt to survive at high temperature.

Of the hundreds of possible mutations, only five proved successful in allowing the cells to adapt and survive at high temperature. Each of these had mutations in a gene that creates a key enzyme that helps make energy at high temperature. Each of the five made a slightly different version of the enzyme.

"One of these five eventually won out entirely and drove all the others to extinction," said Shamoo, associate professor of biochemistry and cell biology and director of Rice's Institute of Biosciences and Bioengineering. "The question is what physical advantage did that particular mutant have? What were the precise physical changes to the enzyme that allowed that strain to outcompete its cousins?"

Finding the answer to that question was painstaking. While the were known from the earlier study, it fell to graduate student Matt Peña to find out how small changes in the of the bacteria translated into specific enzymatic changes. He found that adaptation depended critically on simultaneously keeping the enzyme working while also increasing its resistance to inactivation as the temperatures increased.

He found that versions of the enzyme -- which is a specific kind of protein -- that became inactive were also subject to protein misfolding. In humans, an inability to maintain properly folded and active proteins has been linked to several human diseases, including Alzheimer's.

"Studies like this can help us understand the physical basis for these kinds of diseases, and they can give us a better understanding for the molecular basis for adaptation," Shamoo said. "For example, what we learn from these thermophiles carries over into our work on drug-resistant bacteria because the principles of adaptation are the same no matter whether you're studying temperature, pH, or whatever," he said.

Shamoo's lab won funding from the National Institutes of Health in 2009 to study how evolve antibiotic resistance. One of the ultimate goals of the project is to predict how evolution will play out so that drugmakers can head off resistance before it arises.

"With the thermophile study we've shown that it is possible to build a fitness function -- a mathematical expression -- that translates enzyme performance into a specific measure of competitive advantage," Shamoo said. "That's important because if you can't do that for one protein of interest, then there's no way you're going to be able to do it for a more complicated problem like antibiotic resistance, which involves simultaneous mutations to more than one gene."

Explore further: How do our muscles work? Scientists reveal important new insights into muscle protein

add to favorites email to friend print save as pdf

Related Stories

Ready, set, mutate... and may the best microbe win

May 18, 2006

Even with modern genomic tools, it's a daunting task to find a smoking gun for Darwinian evolution. The problem lies in being able to say not just when and how a specific gene mutated but also how that one genetic change ...

The structure of resistance

Feb 22, 2008

A team of scientists from the University Paris Descartes has solved the structure of two proteins that allow bacteria to gain resistance to multiple types of antibiotics, according to a report in EMBO reports this month. ...

Researchers discover a way to strengthen proteins

Dec 10, 2009

Proteins, which perform such vital roles in our bodies as building and maintaining tissues and regulating cellular processes, are a finicky lot. In order to work properly, they must be folded just so, yet many proteins readily ...

Recommended for you

Genomes of malaria-carrying mosquitoes sequenced

4 hours ago

Nora Besansky, O'Hara Professor of Biological Sciences at the University of Notre Dame and a member of the University's Eck Institute for Global Health, has led an international team of scientists in sequencing ...

How calcium regulates mitochondrial carrier proteins

Nov 26, 2014

Mitochondrial carriers are a family of proteins that play the key role of transporting a chemically diverse range of molecules across the inner mitochondrial membrane. Mitochondrial aspartate/glutamate carriers are part of ...

Team conducts unprecedented analysis of microbial ecosystem

Nov 26, 2014

An international team of scientists from the Translational Genomics Research Institute (TGen) and The Luxembourg Centre for Systems Biomedicine (LCSB) have completed a first-of-its-kind microbial analysis of a biological ...

Students create microbe to weaken superbug

Nov 25, 2014

A team of undergraduate students from the University of Waterloo have designed a synthetic organism that may one day help doctors treat MRSA, an antibiotic-resistant superbug.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.